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Professor Mycek officially appointed as BME chair

Professor Mary-Ann Mycek has been appointed the William and Valerie Hall Department Chair of Biomedical Engineering (BME), effective September 1, 2023, through August 30, 2028. U-M Regents voted on September 21, 2023, to confirm her appointment.

Professor Mycek has served as interim chair of BME since July 1, 2021. As interim chair, she was responsible for the education and welfare of more than 650 BME undergraduate and graduate students, while 13 new faculty members joined the department. She also served as the principal investigator for the Coulter Translational Research Partnership Program in BME – a $20M endowed program with a goal of creating a powerhouse of innovation in BME. The BME Coulter Program supports research directed at promising technologies within research laboratories that are progressing towards commercial development and clinical practice. As interim chair, Professor Mycek supported the development and implementation of several academic initiatives, including launching the first Master’s of Engineering degree program in BME, initiating the ongoing BME Exchange networking program for students, alumni and industry partners, and developing and launching BME Summer Workshops @ Michigan – an annual series on focused translational research topics for global participants hosted on-site by BME faculty, staff and students.

“I enjoyed working with Professor Mycek when she was associate dean and appreciate the unique perspective she brings to this role,” said Steve Ceccio, interim dean of Michigan Engineering. “I look forward to her continued leadership and collaboration as the William and Valerie Hall Department Chair of Biomedical Engineering.”

“We greatly appreciate Dr. Mycek’s strong leadership as interim chair since 2021, and we are thankful that she will now serve as chair of BME, said Marschall S. Runge, MD, PhD, dean of the U-M Medical School. “During her tenure, BME has made tremendous strides in education and research, and we have every confidence that Dr. Mycek will lead the department to even greater heights during the next five years.”

“I’m truly honored to be appointed the William and Valerie Hall Department Chair of Biomedical Engineering at the University of Michigan,” said Professor Mycek. “I’m immensely proud of our U-M community of nearly 1,000 BME students, postdocs, research scientists, staff, and faculty, and the important work they do every day to realize our research and educational mission. Moving forward, I’m excited to work with the broader BME community and our friends to further promote and enable BME’s mission, and to expand the department’s impact for the benefit of humanity.”

Professor Mycek received her PhD in physics from the University of California at Berkeley, where she specialized in condensed matter physics and ultrafast optical spectroscopy, before pursuing postdoctoral training in laser medicine at Massachusetts General Hospital and Harvard Medical School. She was appointed as an assistant professor at Dartmouth College in 1998. Professor Mycek joined the faculty at U-M as an associate professor in 2003 and was awarded tenure in 2006. She has served as an associate chair of the BME Department twice: first as director of the BME Master’s and doctoral graduate programs and later as the associate chair for translational research. She was promoted to professor in 2012, and was appointed the associate dean for graduate education in Michigan Engineering in 2016. In 2018, her responsibilities were expanded to include online and professional engineering education and she was appointed the associate dean for graduate & professional education. In 2021, she was appointed the interim chair of the department of biomedical engineering, a joint department in the Michigan Engineering and the Medical School.

As associate dean for graduate and professional education, Professor Mycek served as the chief academic officer for graduate education in Michigan Engineering and was responsible for the education and welfare of more than 3,600 Master’s and PhD students engaged in over 60 graduate engineering degree programs. She was also responsible for the education and welfare of more than 1,900 Michigan Engineering online students and lifelong professional education learners. As associate dean, she co-led the Education pillar of our ME 2020 strategic vision, creating and implementing strategic initiatives and assessment plans related to CoE graduate, online, and professional education. In 2018, she established the NextProf Nexus partnership with UC Berkeley and Georgia Tech. The partnership expanded access to Michigan Engineering’s NextProf Future Faculty Workshop, which is designed to encourage graduate students and postdoctoral fellows in traditionally underrepresented demographic groups to pursue academic careers. In 2019, she launched Nexus, Michigan Engineering’s home for online and professional engineering education. Established just prior to the pandemic, Nexus provided both strategic and operational advantages during the remote-learning transition.

A researcher in biomedical photonics, Professor Mycek has been elected to the College of Fellows of the American Institute for Medical and Biological Engineering (AIMBE) and is a fellow of SPIE – The International Society for Optics and Photonics. Her translational research program involves developing and applying methods of optical science and engineering to quantitatively probe living cells and tissues, with the long-term goal of impacting patient care via the development of non- and minimally-invasive biophotonic diagnostic technologies. The research strategy she employs includes optical molecular imaging, clinical optical diagnostics, and computational modeling for quantitative tissue diagnostics, with diverse applications including early cancer detection, tissue engineering, and regenerative medicine. The scope and significance of her contributions to science and engineering are evidenced by her peer-reviewed publications (more than 175 journal articles, book chapters, and conference proceedings), scientific presentations (more than 165 invited and contributed talks and posters), and intellectual property (seven issued U.S. patents).

Professor Mycek’s wide range of experiences and achievements in translational research and inclusive, institutional leadership will be invaluable as BME continues to solve important challenges in medicine and life sciences to the benefit of humanity.

AI tool helps optimize antibody medicines

Machine learning points out why antibodies fail to stay on target, binding to molecules that aren’t markers of disease—and suggests better designs.

BY: DEREK SMITH

Antibody treatments may be able to activate the immune system to fight diseases like Parkinson’s, Alzheimer’s, and colorectal cancer, but they are less effective when they bind with themselves and other molecules that aren’t markers of disease. Now, new machine-learning algorithms can highlight problem areas in antibodies that make them prone to binding non-target molecules.

“We can use the models to pinpoint the positions in antibodies that are causing trouble and change those positions to correct the problem without causing new ones,” said Peter Tessier, the Albert M. Mattocks Professor of Pharmaceutical Sciences, Chemical Engineering, and Biomedical Engineering at the University of Michigan and corresponding author of the study in Nature Biomedical Engineering.

“The models are useful because they can be used on existing antibodies, brand new antibodies in development, and even antibodies that haven’t been made yet,” Tessier added.

Antibodies fight disease by binding specific molecules called antigens on disease-causing agents—such as the spike protein on the virus that causes COVID-19. Once bound, the antibody either directly inactivates the harmful viruses or cells or signals the body’s immune cells to do so.

Unfortunately, antibodies designed to bind their specific antigens very strongly and quickly can also bind non-antigen molecules, which removes the antibodies before they target a disease. Such antibodies are also prone to binding with other antibodies of the same type and, in the process, form thick solutions that don’t flow easily through the needles that deliver antibody drugs.

“The ideal antibody should do three things at once: bind tightly to what they’re supposed to, repel each other and ignore other things in the body,” Tessier said.

An antibody that doesn’t check all three boxes is unlikely to become a successful drug, but many clinical-stage antibodies can’t. In their new study, Tessier’s team measured the activity of 80 clinical-stage antibodies in the lab and found that 75% of the antibodies interacted with the wrong molecules, to one another, or both.

Changing the amino acids that comprise an antibody, and in turn the antibody’s 3D structure, could prevent antibodies from misbehaving because an antibody’s structure determines what it can bind. But, some changes could cause more problems than they fix, and the average antibody has hundreds of different amino acid positions that could be changed.

“Exploring all the changes for a single antibody takes about two workdays with our models, which is substantially shorter compared to experimentally measuring each modified antibody—which would take months, at best,” said Emily Makowski, a recent PhD graduate in pharmaceutical sciences fand the study’s first author.

The team’s models, which are trained on the experimental data they collected from clinical-stage antibodies, can identify how to change antibodies so they check all three of those boxes with 78% to 88% accuracy. This narrows down the number of antibody changes that chemical and biomedical engineers need to manufacture and test in the lab.

Two men wear white lab coats, blue nylon gloves, and safety goggles while standing at a black lab bench. On the bench are several flasks filled with a yellow-brown fluid and test tubes in racks. Tessier, on the left, appears to dispense something into a tube while Tiexin, on the right, holds a centrifuge tube with a blue cap that contains a clear liquid. — Peter Tessier (left) and Tiexin Wang (right), a doctoral student in chemical engineering and study co-author, prepare antibodies to test how they bind to themselves and other molecules. Credit: Hye Jin Lee, Tessier Lab, Pharmaceutical Sciences, University of Michigan.

“Machine learning is key for accelerating drug development,” said Tiexin Wang, a doctoral student in chemical engineering and study co-author.

Biotech companies are already beginning to recognize machine-learning’s potential to optimize the next-generation of therapeutic antibodies.

“Some companies have developed antibodies that they are really excited about because they have a desired biological activity, but they know they are going to have problems when they try to use these antibodies as drugs,” said Tessier. “That’s where we come in and show them the specific spots in their antibodies that need to be fixed, and we are already helping out some companies do this.”

The research was funded by the Biomolecular Interaction Technology Center, the National Institutes of Health, the National Science Foundation and the Albert M. Mattocks Chair and was conducted in collaboration with the Biointerfaces Institute and EpiVax, Inc.

The University of Michigan and Sanofi have filed a patent application for the experimental method that provided the data used to train the algorithm.

Tessier has received honoraria for invited presentations on this research from GlaxoSmithKline, Bristol Myers Squibb, Janssen and Genentech.

Study: Optimization of therapeutic antibodies for reduced self-association and non-specific binding via interpretable machine learning

Surgeon uses academic development time to collaborate with Biomedical Engineering

Drew Braet is a fourth-year resident in Vascular Surgery and is taking his two-year academic development time to work with C. Alberto Figueroa, the Edward B Diethrich M.D. Research Professor of Biomedical Engineering and Vascular Surgery, professor of surgery, Medical School and professor of biomedical engineering, Medical School and College of Engineering. Dr. Braet’s goal from this collaboration is to gain a better understanding of determining which patients are most likely to benefit from surgical intervention.

“I sought to work with Biomedical Engineering, and Dr. Figueroa, specifically, by choice,” Dr. Braet said. “Early in my training, I became frustrated with the lack of information we often have about vascular disease, particularly when looking at which patients we should or should not offer surgery to. It’s pretty typical in medicine that things aren’t black and white, and that there are many gray areas. We’re really lacking clear data in a lot of different realms that can help us with decision making.”

“It is not typical that a surgeon would do research in an engineering laboratory like ours,” said Dr. Figueroa. “To have someone who goes from operating on patients to then spending two years learning analytical tools–imaging tools, modeling tools and computational tools–is somewhat unique.” A two-year research period is mandatory at U-M, but most people in the training program do not end up focusing on Engineering. “Historically, most trainees do time working in a basic science wet laboratory,” he added.

Dr. Braet was researching information in his quest to learn more ways data analysis can inform surgical interventions, and through a Google search, came upon Dr. Figueroa’s lab.

“I thought what he was doing in using computational methods in advanced imaging analysis would really help me,” Dr. Braet said. “I wanted to learn a tool set to be able to explore some of the questions I had. I ultimately want to improve our understanding and to provide better patient care. We met early on in my intern year. I heard about some of the work they were doing in the lab and explained some of the things I was interested in. In my intern year, we started doing a smaller project. Dr. Nick Burris, a radiologist, and I worked on that for a year, and we were able to publish a paper. From there, we started thinking about a bigger project that we could do during my dedicated time, and that led us to do my current project and current NIH F32 fellowship, where I’m looking at patients with high-grade asymptomatic carotid artery disease.”

The carotid artery is the artery in your neck that goes to your brain. “Patients who have narrowings in that artery have buildup of cholesterol plaque, the same kind of plaque that can lead to heart attacks,” Dr. Braet said. “That plaque can break off, and cause a stroke. The way that we think about these plaques in medicine is based on historical studies which suggest that the percentage of narrowing of the carotid artery is related to the risk of having a stroke. When I think about that from a biophysical and biomechanical standpoint, it doesn’t make sense. Not to discredit the studies that were previously done, this is what science has shown and we have helped a lot of people by thinking that way. But when you really boil it down to the biophysics of blood flow, that doesn’t make sense, because plaques rupture when the forces exerted on them exceed the strength of the tissue. We’re doing a computational modeling study by looking at the pressure differences, the velocity differences and the wall shear stress on carotid artery plaques to try to get a better understanding of the hemodynamic strains and stresses of the plaque and thus the risk of stroke. This could potentially lead to an entirely new way of looking at the way patients present with this particular issue. In a perfect world, 20 years from now, it would be great if the medical field could be using some of the things that we’re studying today. These kinds of engineering, imaging and modeling analyses, I think, will help us do a much better job with risk stratification that ultimately will determine whether to perform surgery or to watch a patient more conservatively.”

Dr. Braet noted that it is “refreshing” to learn to examine problems in a different way. ”In the big picture, if more surgeons and more doctors learned to look at challenges differently, we might be able to be more creative in the treatments that we can offer,” Dr. Braet said. The analysis of big data and the use of technological innovations are playing increasingly important roles in medicine, and Dr. Braet wants to understand how Engineering can assist the profession.

Dr. Figueroa noted the value of this type of mentorship for the mentor as well as the mentee. “It’s interesting because someone like Drew has a very different background and very different ways of seeing a problem than someone from a traditional engineering background,” he said. “Everybody talks about translation and reaching out, and when you are in engineering, you want to have your tools applied, but it’s actually quite difficult to do because of how distant the training and the day-to-day professional thought processes these two groups have. In engineering, you typically say you want to talk to clinicians because at the end, they are your customers for developing a new device or a new diagnostic procedure. Eventually, they’re going to have to use it and understand it, right?”

The fact that the University of Michigan has a Biomedical Engineering Department that is jointly in both the Medical School and in the College of Engineering enhances these opportunities for collaboration. There are a lot of institutions out there where perhaps they have a biomedical engineering department, but they don’t have a medical school,” Dr. Figueroa said. “In those institutions, this understanding is much harder to achieve because the engineering folks are kind of isolated and they don’t have ready access to clinical peers.”

Dr. Figueroa added that the opportunity to serve as a mentor is a rewarding experience, professionally and personally. “To me, it’s important that when I one day finish my career, I will have contributed to training a small group of clinicians who have an engineering thought process,” he said.

Student Innovator Team ‘Enginuity’ Selected for Honorable Mention at the 2023 DEBUT Challenge

U-M’s student innovator team, Enginuity, was recently selected for an honorable mention at the 12th annual Design by Biomedical Undergraduate Teams (DEBUT) Challenge. Enginuity was selected for their innovation’s ability to create a positive impact by addressing health and clinical challenges.

Millions of people in the U.S. have neurogenic bladder disorder. Treated through clean intermittent catheterization (CIC), the process can be time-consuming and ineffective and result in complications like infections or kidney stones. Enginuity developed Fast-Cath, an accessible, portable device that drains and irrigates bladders while maintaining safe pressure, flow, and urine volume levels.

Congratulations to:

Team Captain: Jayanth Tatikonda
Team Members: Connie Gao, Benjamin Gerber, Ritika Pansare, Joel Pingel
Faculty Sponsor: Dr. Rachael Schmedlen

Enginuity will be recognized at the the Annual Meeting of the Biomedical Engineering Society in October 2023. The DEBUT Challenge is oriented toward undergraduate student teams working on innovative solutions for real-world problems in healthcare. Submissions were judged on the basis of the significance of the problem being addressed, the impact of the proposed solution on potential users and clinical care, the ingenuity of the design, and whether the solution had a working prototype.

The National Institute of Biomedical Imaging and Bioengineering (NBIB) and VentureWell have
partnered to support the DEBUT Challenge, and together have awarded a total of $145,000 in
prizes for 2023. The winners of the DEBUT Challenge will be honored at an award ceremony
during the Annual Meeting of the Biomedical Engineering Society in October 2023.

U-M BME alum credits family, education as inspiration for decision to attend Medical School

Devak Nanua (BSE, MSE) entered the world at Michigan Medicine and credits the life-saving leukemia treatment his mother received there while pregnant with him as part of the foundation for his desire to pursue Medical School.

Nanua, whose parents emigrated from India, described the excitement with which his father and mother arrived in Ann Arbor and their joy in planning to start a family. However, they would encounter serious challenges to fulfilling their dreams along the way.

“My mom was, unfortunately, diagnosed with leukemia in her late 20s,” Nanua said. “For a 27-year-old to be given that moment of facing her own mortality, it had to be so hard for her, especially having just come to this country.”

During his time as a student at U-M, Nanua was able to learn about his mother’s medical journey through the research notes and firsthand accounts of physicians and medical personnel who had provided her care two decades ago.

“She was given two options,” Nanua noted. “If she did start the traditional drug treatment at that time, it would have meant aborting me. It was a challenging decision. My parents had said that the best news they received that week was that they were expecting a child. My mom knew that her fertility would be limited down the road once starting treatment. Having newly immigrated, it was especially daunting to be facing this and having to make such decisions. At Michigan Medicine, she had a great team of physicians and oncologists. I read the story of my parents and how I came into the world. Everyone here worked with her and supported her. The only curative modality was for my mother to have a bone marrow transplant from my younger aunt, who was only a teen at the time living in India.”

Nanua’s mother successfully had the bone marrow transplant, and eventually recovered. “She was able to have me without complications,” Nanua said. “My mom got a second lease on life.”

Nanua added that as a child, he did not initially know or understand the magnitude of the health issues his mother had faced. “Throughout my years of growing up, there was a feeling of gratitude and a feeling of thankfulness toward the medical system that I picked up on from my mom,” he said. “I knew the relationship my mom had with her caregivers and the trust she placed in them. Even as a young kid, I was inclined to think about medicine in general terms as a possible career.”

When Nanua entered college, he ended up studying BME for his undergraduate and master’s degrees. “One thing that stuck out to me during my time in BME was my experience in our undergrad senior design project,” he said. “It was this great opportunity to work with a diverse team of clinicians and engineers to solve a problem at the hospital. I realized I ultimately wanted to work in a space where patients can have the opportunity to experience an easier journey to health, despite their terrible ordeal.”

Nanua enjoyed the challenges that BME offered. “I had fun being an innovator on the engineering side, but it was only through meetings with clinicians, where they were able to point out important design considerations, that I saw issues from their perspective,” he said. “I felt like I needed a clinical experience background to become a more efficient engineer in order to innovate in the space that I wanted.”

Nanua said U-M’s BME program offers students a rich curriculum. “I really appreciated the variety of courses that I got to take as a BME student,” he said. “By the time students are in their senior year here, they have studied aspects of the human body through the perspectives of mechanical engineering, materials engineering, electrical engineering, chemical engineering and computer engineering. By learning about the human body through the lens of different disciplines, it gives you enough tools to be creative and participate in many research projects or biomedical device design projects.”

As part of Nanua’s desire to make an impact through his work, he recently returned from a medical service trip to Rwanda. “As a medical student, I am a part of the Global Health and Disparities path of excellence,” he said. “Through this elective, I am able to learn about and discuss topics of health inequities and disparities in a global and domestic setting along with my peers and faculty who work in these spaces. At the end of our first year of medical school, we have a six-week break where students can take some time to do whatever they want. I was always curious about the challenges of practicing medicine in an international and low resource setting. While being a part of this path of excellence, I had the pleasure to meet Dr. David Bradley, who is a Pediatric Cardiologist at Michigan who had been recently working in Rwanda. While meeting him, I was incredibly inspired by the work that he was doing, and this encouraged me to travel to Rwanda during my break.”

Through Dr. Bradley’s guidance and grant funding from Michigan Medicine, Nanua worked at the Centre Hospitalier Universitaire de Kigali (CHU-K) for several weeks. CHUK is the primary teaching hospital in Rwanda. During his time there, he participated in short clinical rotations where he primarily shadowed doctors in pediatrics, pediatric surgery and general surgery.

“I was surprised that even after just completing my first year of medical school, I knew a lot more than I thought and was able to keep up with the pace of being on the wards,” he said. “I was able to learn a lot about clinical concepts through the rich discussions that I’d have with doctors, residents, nurses and other medical students who I worked with. It was also incredible to experience what life looks like in another culture – specifically what healthcare looks like in a primarily low-resource setting. Having lived in Ann Arbor for the majority of my life, I’ve been incredibly fortunate and privileged to obtain care from and now train at a hospital where there are no shortage of resources, opportunities and highly trained physicians who I am lucky to call my mentors. While a lot of the care at CHU-K is still limited by its resources and a lot of the clinical presentations I saw were influenced by living in poverty, it was incredibly inspiring to go to work with a team of doctors who continued to try to do the best they could by their patients despite being aware of the limitations. It’s this attitude and energy for service that I hope to carry with me as I continue my medical education.”

U-M BME Hosts Orientation to Welcome Grad Students

U-M BME held its annual graduate student orientation on Tuesday, August 22, to welcome Master’s and PhD students to the new academic year and provide an overview of their respective programs. One of the session’s goals was also to build a sense of community; more than 120 students attended.

“The best predictor of your success in graduate school – this means your successful completion of the BME graduate program and your successful launch into the next phase of your professional lives – is your sense of belonging in our BME community,” said Mary-Ann Mycek, BME Interim Chair and professor of biomedical engineering, during her opening remarks.

“That’s why I was delighted to see the orientation program that our graduate education team has created for you today. This will be a wonderful introduction to the broader BME community and will hopefully help you as you find your place in it,” she added.

Following introductions from faculty and staff, students learned about the variety of organizations in which they can become involved and details about their curricula. Students met with their program advisors in small groups (based on concentration) to formulate academic plans.

“This meeting not only provided academic structure to their program, but also provided students an opportunity to meet directly with other students who are passionate about the same focus areas, thus creating a peer support group of people who will be taking many classes with each other,” said Rachel Patterson, BME Student Administration Manager.

“Current graduate students, led by Sydney Wheeler and Mary Dickenson, did a fantastic job at welcoming and integrating new students with the orientation activities they planned,” said Tim Bruns, BME Associate Chair for Graduate Education, biomedical engineering and associate professor, biomedical engineering.

For more information about BME student organizations, please visit this link. For information about the BME Graduate Student Council, which led many orientation activities, please visit this link.”

BME alum blends her personal, professional passions to advocate for equity and accessibility in healthcare and medical devices

Nicole Bettè (BME BSE, 2016) is a Senior Human Factors Engineer whose personal experiences have informed and inspired her professional goals. In addition to her position with Kaleidoscope Innovation and Product Design, where she works as part of a team based at Eli Lilly in Indianapolis, Indiana, Bettè is Ms. Wheelchair New Hampshire USA 2023 and former Gilman Alumni Ambassador 2022-2023.

“I decided to join the Ms. Wheelchair USA program and apply for the Ms. Wheelchair New Hampshire USA title in order to have greater visibility for my platform, which is accessibility of healthcare and medical devices,” Bettè said. “As a Senior Human Factors Engineer, I’m in a great position to advocate for the accessibility of medical devices, both within the organizations where I work and also as a speaker at technical Human Factors Engineering conferences. I also reach out to disability advocacy organizations and ask for relevant stories directly from the voices of disabled people so that I can better advocate. Although my focus is on disability, I consider other aspects of accessibility as well, such as access barriers or inequity due to race/ethnicity, gender/sex, anthropometrics, etc.”

Bettè knew she wanted to dedicate her life to healthcare and medical devices. “I loved how much BMEs get to learn about different disciplines since it’s such a multidisciplinary field,” Bettè said. “Due to my educational background, I’ve been able to have in-depth technical conversations with mechanical engineers, electrical engineers, chemical engineers, material science engineers, industrial engineers, a variety of scientists, and a variety of medical professionals. Not many people can say that! I’ve always been naturally curious about a wide variety of subjects even while my heart was rooted in healthcare, so BME felt like a very natural degree to pursue as it kept my brain engaged in all sorts of ways.” Bettè also loves engineering, and discovered that BME was the perfect way to fuse her interests. “When deciding between a biology-focused science and biomedical engineering, biomedical engineering felt more natural to me as it’s more application-based,” she added. “I’ve always been a very creative thinker and fixer. I needed the engineering skills in order to channel all of that creativity and drive and turn it into practical solutions and real-world applications.”

Bettè’s journey to her degree and career encountered serious challenges along the way–challenges that would focus her career path to help others. “I struggled with illness and disability throughout college and spent what sometimes felt like half the time at medical appointments and emergency rooms,” she said. “I only had time and energy for academics, one or two extracurricular activities, and that’s it. I had practically no social life because any time outside of academics was spent looking for answers, or I was too ill to do anything. I didn’t know what was wrong. I was getting worse and was so afraid that I was dying that I signed up for a life insurance policy just before I began the arduous journey of seeking a diagnosis so that if I died young, my low-income parents wouldn’t have to shoulder the burden of the six-figure debt I had gotten myself into. Furthermore, toward the end of my academic career, I was working two jobs at almost minimum wage and had to rely on food stamps and food pantries to survive.”

Through grit and determination, Bettè graduated with honors. “That picture of me in my graduation gown that a U-M photographer took captured the pure joy and pride I felt at that moment,” she said. “When I entered that stadium for my graduation ceremony, I had earned it. I had defied all the odds that told me that I wouldn’t graduate because I was poor, Latina, neurodivergent, disabled, chronically ill, a child of a divorced mother who had dropped out of college, and raised by a Cuban grandmother who only had a middle school education and who unfortunately knows what it’s like to have to share bubble gum with her four siblings and to have to survive on the broth from the same bone multiple meals in a row. All in all, it took me three years longer than my peers to graduate, partially due to health reasons and partially due to internships, a few extra classes, and a semester studying abroad.”

Bettè’s health issues have stabilized and are now manageable. “I’m happy to report that I finally have a diagnosis (hypermobile Ehlers-Danlos Syndrome, a genetic connective tissue disorder), and no, I’m likely not going to die young,” she said. “I love my life and I love my job, and I have the help that I need. I’m disabled and proud of it, as my disability is a part of me and it has shaped the way I view life, has opened my heart and my mind to different perspectives, and has given me the experience, knowledge, and empathy to do what I do at work and do it well.”

Bettè encourages students who are facing challenges to reach out to the U-M community and to access available resources. “If you’re struggling with disability, don’t be afraid or ashamed to self-advocate, ask for help, and take advantage of every resource and accommodation U-M has to offer, just as I did,” she said. “U-M did an amazing job at retaining me. They have an impressive amount of structure and resources in place to help disabled and chronically ill students succeed. The staff and I were all very resourceful so that I could make it to that stadium and graduate. So, if you can, graduate. Disability in this country impoverishes most of us. It’s only because of my level of preparation and education that I’m not in poverty right now. I recognize that education in the U.S. is in great part a privilege, but if you happen to have made it this far as a student here and you’re vacillating between finishing and dropping out, finish, even if it means taking longer. I recommend working very closely with your professors and university staff, managing your schedule to give yourself time to rest and go to medical appointments, reducing your course load, mixing and matching hard courses with easier ones when possible, surrounding yourself with a strong positive support system of classmates, mentors, friends, and family who can help you, and, if necessary, taking a break (medical leave/sabbatical). There are also grants and scholarships available to help retain students who are in tough financial situations.”

Bettè believes that the need for diverse representation is great, and that bringing people who will advocate for equity and inclusion will improve accessibility for others in the future. “On that note, there are few disabled healthcare professionals and few disabled medical device engineers like me,” she said. “I wish to see more of us, so that our voices are represented and heard in this industry. I sincerely believe the lack of representation contributes to the access barriers we face in our healthcare system today (which includes inaccessible medical devices/equipment).”

Bettè explained that as a human factors engineer, she considers user safety, effectiveness, and ease of use as well as interface design accessibility, facility accessibility, and the inclusion of a wide variety of participants in usability studies, including disabled participants. In terms of design, she thinks about multiple aspects of accessibility including, but not limited to, these five things:

Enabling the design to provide information in multiple ways (not just visual or just auditory information) and receive information in multiple ways (not just typing or just speaking).
Simplifying the design and the instructions as much as possible to reduce the cognitive burden and complexity required to use it. This helps users’ ability to remain independent when using the device, reduces or sometimes eliminates the need for training, and reduces the likelihood that a use error will happen.
Optimizing the ergonomics of both physical and digital interfaces so that users are able to comfortably use the device (with one hand, for example).
Ensuring that the system or design works just as effectively and accurately for everyone who will use it. For example, sometimes optical devices don’t work as well for people with dark skin as they do for light skin, and with optical medical devices such as pulse oximeters and forehead thermometers, this can have adverse clinical impacts on people, hence its importance in health equity. Similarly, some devices don’t work as well on larger people compared to thinner people.
Leveraging universal and inclusive design principles across the entire development process.

Bettè is committed to reaching out to others so that their voices can also be heard. “If you want to share your story pertaining to access barriers in healthcare, please feel free to reach out to me at bettenicole@gmail.com,” she said. “Stories are the single most powerful tool we have for advocacy! Please share yours with me!”

To help advocate for healthcare equity and inclusion, especially medical device accessibility, use the #AccessibleMedTech hashtag that Bettè created on social media.

If anyone is interested in learning more about or applying to the Ms. Wheelchair USA disability pageant, visit https://www.mswheelchairusa.org/. Ms. Wheelchair USA is run by The Dane Foundation, a 501(c)(3) nonprofit organization with a mission of improving the quality of life of people with physical and developmental disabilities. To learn more about The Dane Foundation, visit http://www.thedanefoundation.org/.

U-M BME-led study reveals the key role of anti-tumor neutrophils in suppressing lung metastasis of breast cancer

A U-M BME-led study published in Nature Communications on August 8 reveals the multifaceted roles of neutrophils in regulating lung metastasis in breast cancer and underscores the key role of neutrophils with anti-tumor phenotypes in suppressing breast cancer cell growth in the lungs.

This study was led by Dr. Lonnie Shea, the U-M BME Steven A. Goldstein Collegiate Professor with appointments in surgery and chemical engineering, and Dr. Jacqueline Jeruss, U-M Associate Dean for Regulatory Affairs, Associate Vice President for Research, and professor of surgery, pathology and BME. Dr. Jing Wang, formerly a postdoctoral fellow at U-M BME and currently an assistant professor at Iowa State University, is the first author. Dr. Aaron Morris, U-M BME assistant professor, is a co-author on this work.

The research team employed a subcutaneous biomaterial scaffold implant to mimic the immune environment in metastatic organs and deconstruct complex signals regulating metastasis. The scaffold implant in mouse models of metastatic breast cancer creates a synthetic metastatic niche, an environment that can recruit lung-tropic circulating tumor cells (tumor cells that preferentially migrate to the lungs) yet suppress their growth through potent in situ anti-tumor immunity. In contrast, similar circulating tumor cells seed the lungs, the endogenous metastatic organ for these models, and develop into lethal metastatic tumors as the environment in the lungs becomes immunosuppressive and pro-tumor at this stage of breast cancer metastatic progression.

The team examined why scaffolds and lungs in the same mouse create different immune environments and direct opposite fates of metastatic breast cancer cells. They found that the selective recruitment of neutrophils with different phenotypes from the circulation determines that the overall environment in the scaffold or lungs is immune-stimulatory and anti-tumor or immunosuppressive and pro-tumor, respectively. “Our study indicates that the scaffold implants overproduce chemokines CXCL1, CXCL2, and CXCL5 due to the foreign body responses to scaffold implants.” Dr. Wang said. “And these chemokines recruit anti-tumor neutrophils from the circulation to activate tumor-killing effector cells (CD8⁺ T cells and NK cells) to clear tumor cells seeding the scaffolds. In contrast, the lungs in mice with metastatic breast cancer overproduce S100A8/A9 protein complex to recruit pro-tumor neutrophils that suppress the activity of effector cells and support tumor cell growth.” A scheme is provided in Figure 1.

Additionally, their findings from the synthetic metastatic niche further explain why the lungs from the host with non- or weakly metastatic breast cancers do not develop metastatic tumors. In contrast to the lungs in the setting of metastatic breast cancer that are dominated by pro-tumor neutrophils and deactivated effector cells, the lungs in non- or weakly metastatic breast cancers overproduce CXCL1, CXCL2, and CXCL5, possibly due to immunoediting of primary tumors, to recruit and enrich anti-tumor neutrophils and create an environment with potent anti-tumor immunity that prevents the growth of metastatic cells.

“Our findings have been validated and may have clinical implications. A high ratio of signals that recruit anti-tumor neutrophils (Cxcl1, Cxcl2, or Cxcl5 genes) to signals that recruit pro-tumor neutrophils (S100a8, or S100a9 genes) was positively correlated to a low chance of developing metastasis in our study. This ratio may help to predict the risk level of lung metastasis for patients with breast cancer.” said Dr. Wang. Dr. Shea added that the scaffolds are being developed for a clinical study, and this ratio could be derived from the scaffold, thereby providing an opportunity to assess metastatic disease and guide patient management without an invasive biopsy of vital organs.

Wang added: “Our findings also have therapeutic implications, as this mechanistic study will inspire new anti-metastasis therapy strategies directed towards changing the signals in the lungs from those recruiting pro-tumor neutrophils to those recruiting anti-tumor neutrophils.”

A screenshot of a computer screen

Description automatically generated

Figure 1. Schematic illustration of the selective recruitment of anti-tumor and pro-tumor neutrophils to the lungs of animal models of breast cancers with varying tumor aggressiveness responding to distinct groups of chemokines/cytokines that attract neutrophils, followed by creation of an environment in the lungs that supports or suppresses growth of breast cancer cells.

**Researchers share advances in vision research during BME Summer Workshops @ Michigan meeting**

More than 65 researchers participated in the first BME Summer Workshops @ Michigan meeting on August 11-12. The Biomedical Engineering Department partnered with Ophthalmology and Visual Sciences to co-host the workshop on imaging and therapy in vision research, which featured 25 speakers highlighting their latest research. The small-group setting provided a forum for the exchange of technical information, allowing attendees to engage in dialogue with presenters.

“The goal of the BME Summer Workshops @ Michigan series is to establish the University of Michigan in Ann Arbor as a place to gather, learn, and network – each year – in the summer, when the weather is so wonderful – on important research topics in BME,” said Mary-Ann Mycek, Interim Chair and Professor of Biomedical Engineering. “I want to thank our colleagues at U-M Ophthalmology & Visual Sciences in the Kellogg Eye Center for committing to co-host the 2023 workshop with us and for developing the exciting agenda. I am especially grateful to Professors Gary Xu and Xueding Wang for co-organizing this year’s workshop.”

“The speakers did a great job of interacting with everyone in both departments,“ said Gary Xu, U-M Assistant Professor of Biomedical Engineering and Ophthalmology departments and a co-organizer of the event. “The interaction between the external speakers and internal researchers is very important. When we can talk personally to other researchers, we can gain a greater understanding of different perspectives, helping us all to move forward in our research.”

“I think this event showcases the engineering powerhouse that Michigan really has here,” said Juliette McGregor, Assistant Professor of the Department of Ophthalmology and Visual Sciences at the University of Rochester. Professor McGregor was one of several invited speakers from outside U-M to present. “There has been material ranging from the genetic modification of new animal models, to some of the more sophisticated imaging approaches, and then discussion about robotic-assisted surgery. It’s been great to hear from speakers here as well as invited speakers from around the country. This has really had a workshop feel, where you can try to help each other and share common issues and experiences, in addition to showcasing what you do,” McGregor said.

“The co-organizers did a great job of highlighting outstanding research, both at U-M and around the country,” said Joseph Izatt, the Michael J. Fitzpatrick Distinguished Professor of Engineering, and Chair of BIomedical Engineering at Duke University, and an invited presenter. “The size of the event was nice,” he added. “I think that the mix of internal research with a few invited outside guest speakers worked out well.”

“I would like to see this as a yearly event for all of us to come together,” said Dorsa Ghaffari, a postdoctoral researcher in the lab of Jim Weiland, U-M Associate Chair for Research in Biomedical Engineering and Professor, Biomedical Engineering and Professor, Ophthalmology and Visual Sciences. ”I like the small-group format because this setting helps you feel more comfortable to ask follow-up questions and interact more with the speakers.”

Jeanpaul Passo, an incoming PhD student who will also be in Professor Weiland’s lab, agreed with Ghaffari, and added that this exchange of ideas helps researchers approach issues in different ways. “It’s refreshing to see what other lab groups are working on and how they are approaching various topics. The smaller setting also has a community feel, so it’s easier to have your voice heard in the discussion.”

BME launches new Advanced Medical Product Engineering and Development (AMPED) Master’s program in Fall 2023

U-M BME is excited to launch a new Master of Engineering (MEng) degree designed for those who want to make an impact in the medical technology industry. The Advanced Medical Product Engineering and Development (AMPED) program offers an experiential product realization practicum (design-build-test) with a focus on quality systems, risk management and regulatory structures. It also includes courses on advanced topics in medical product development, as well as professional and leadership development.

The first cohort of 25 AMPED students is starting this fall, and applications for Fall 2024 will open in mid-September. The program is designed to be completed in two to three academic terms, depending on academic background. Successful applicants typically have an undergraduate degree in engineering or the physical sciences and a demonstrated interest in medical product development.

For more information, visit the AMPED program website.

BME student wins first place in poster competition in computational biological systems

Congratulations to U-M BME PhD student Javiera Jilberto Vallejos, who received first place in the category of computational biological systems in a student poster competition, held in conjunction with the 17th U.S. National Conference of Computational Mechanics.

The biennial congress, which happened in New Mexico in late July, is the premier U.S. venue for showcasing the latest research in the broad field of computational mechanics, bringing together top researchers and practitioners in academia, government and industry from around the world.

Jilberto’s poster focused on developing computational models to understand the relationship between the mechanical environment and cardiomyocyte maturation, which is the variety of changes to cell structure, metabolism, function and gene expression that convert fetal cardiomyocytes to adult cardiomyocytes. She created her poster in collaboration with the Baker Lab, where heart tissue is engineered.

“They try to understand how mechanics drive cardiomyocyte maturation, but there are a lot of mechanisms that are difficult to quantify, so we need to use a computational approach,” Jilberto explained. “We wanted to quantify how mechanics were changing the things that the team was observing.”

“They have a lot of data and many images,” she added. “So what I did was take all the images and all the functional information that they have to build a very detailed model of these tissues. For example, in cardiac mechanics, what our lab usually does is to create digital twins, where we grab the images from the patient’s heart and we build a virtual model of that heart. For this project, the idea was to do the same–to capture all the data that they have from these tissues and create a model so that we can better understand how the mechanical response is changing and measure quantities that they cannot typically measure experimentally. We can, for example, measure the stress that the cells are generating instead of relying on a global measure of tissue deformation to assess the mechanical function of the tissues.”

This research is conducted as part of an NSF Engineer Research Center (ERC) grant. Jilberto will be starting her fourth year in August as a student of David Nordsletten, Associate Professor, Department of Biomedical Engineering and Cardiac Surgery. The poster competition rubric focused on technical content, clarity and organization, and the question-and-answer section. Jilberto’s poster was first among nine competitors who were selected from a larger group of applicants to compete.

Histotripsy researchers receive Distinguished University Innovator Award

Histotripsy, a term coined by University of Michigan researchers, is a technique that uses sound waves to break down diseased tissue. Designed as a noninvasive alternative to surgical procedures, the novel technology uses focused ultrasound to mechanically disrupt target tissue, as opposed to thermal ablation.

The technology holds promise to permit patients with diseased tissue, such as cancerous tumors, to obtain treatment with less discomfort and faster recovery times than traditional surgery.

A team led by researchers from the College of Engineering and the Medical School invented and developed histotripsy, and their efforts to bring it to the clinic to address human disease has earned them this year’s Distinguished University Innovator Award. The team members are:

Zhen Xu, professor of biomedical engineering.
Timothy Hall, research scientist in biomedical engineering.
Jonathan Sukovich, assistant research scientist in biomedical engineering.
J. Brian Fowlkes, professor of radiology and of biomedical engineering.
William Woodruff Roberts, professor of urology and of biomedical engineering.

The Distinguished University Innovator Award is the highest honor for U-M faculty members who have developed transformative ideas, processes or technologies and shepherded them to market for broad societal impact. It was established in 2007 and is supported by endowments from the Office of the Vice President for Research and the Stephen and Rosamund Forrest Family Foundation.

“What distinguishes the University of Michigan as a leading public research university is our shared perpetual pursuit of innovative solutions to the greatest challenges impacting communities across the globe,” said Rebecca Cunningham, vice president for research and the William G. Barsan Collegiate Professor of Emergency Medicine.

“Together, we are persistent in our mission to serve the people of Michigan and the world, and as part of this collective commitment, we will continue to support our research discoveries and help translate them into real-world tools and services. What the histotripsy team has developed is a prime example of innovative research that needs to be shared broadly with the world.”

OVPR selected this year’s award recipients based on the recommendation of a diverse faculty selection committee that reviews a pool of nominees. The histotripsy team will receive the award Sept. 14 at the annual Celebrate Invention event at the Michigan Union.

Changing the landscape of surgical treatment

“This highly collaborative team has developed a breakthrough idea with innovative hardware and software to enable the histotripsy process,” said Mary-Ann Mycek, professor of biomedical engineering and interim chair of the department, which is jointly housed in CoE and the Medical School.

MORE INFORMATION

“They’ve published a tremendous amount of data showing histotripsy’s disruptive and transformational potential, created a new subfield and formed a company that is making outstanding progress toward clinical translation and commercialization. The contributions they’ve made are substantial, and I look forward to seeing the team’s future innovations.”

A startup company based on histotripsy, HistoSonics, was launched in 2010 with support from Innovation Partnerships, a unit based in OVPR that serves as a central hub to lead U-M research commercialization efforts.

While minimally invasive and noninvasive technologies are routinely used in the clinic, they have limitations such as bleeding, infection, radiation and heat induced complications. HistoSonics has developed the Edison System, the first noninvasive, non-ionizing and non-thermal procedure to destroy targeted tissues that is guided by real-time imaging, alleviating the limitations of earlier versions. It has accomplished what has been out of reach for others — successfully using sound wave energy to mechanically obliterate diseased tissue.

“We are grateful for the support we received from the University of Michigan on our journey to invent histotripsy and develop it into a platform that can be leveraged broadly to treat patients,” Xu said.

“We would not have accomplished all that we have and come as far as we have without Innovation Partnerships. They have been with us every step of the way to go from an inventor mindset to commercialization.”

HistoSonics now employs more than 100 people and has raised more than $200 million. With a presence in Ann Arbor, HistoSonics embodies what the university strives for in its research commercialization efforts — it not only delivers a product or service that positively impacts patients, it also generates a significant economic impact.

“One of the best parts about science is turning the impossible to possible,” Xu said. “What our team has accomplished by providing an incisionless, non-toxic, painless way to destroy disease tissue via sound wave energy is incredible. I’m excited about the potential of histotripsy to change the field of medicine and cancer treatment, and eventually extend to treat many other disease types beyond cancer, such as stroke, neurological diseases, cardiovascular diseases and skin diseases.”

BME advisor hosts Code Maize podcast episode

This Code Maize episode, produced by Newnan Advising, features two current students at the University of Michigan Medical School. Piroz Bahar and BME alum Devak Nanua discuss their pathways to medicine, as well as the importance of creating bonds with faculty and fellow students as a meaningful part of defining success as an M1 student. Nanua specifically highlights how his BME grad degree prepared him for Medical School. Rachel Patterson, a BME academic advisor and counselor, hosted this podcast episode.

In Memoriam–Professor Raoul Kopelman

U-M BME is saddened to learn about the passing of Professor Raoul Kopelman. Professor Kopelman (1933 to 2023) passed away in Ann Arbor on July 20 at the age of 89. He was a jointly appointed professor of biomedical engineering from 2006 until 2014 and remained an active member of our faculty until his passing.

Professor Kopelman was born in Vienna, Austria, on October 21, 1933. He earned his BS in Chemical Engineering at the Technion, Israel Institute of Technology (1955), as well as an Engineering Diploma (1956) and an MS in Physical Chemistry (1957). He was the first Israeli to receive the US Fulbright Travel Grant (1957). Professor Kopelman earned his Chemistry PhD at Columbia University (1960) and completed his postdoctoral training at Harvard (1960-62).

“Dr. Kopelman was a wonderful colleague with whom our faculty often collaborated, including on dissertation committees and research projects,” said Mary-Ann Mycek, Interim Chair and Professor, Biomedical Engineering. “He had a generous nature and enjoyed sharing his love of learning with our community. He will be greatly missed.”

Dr. Kopelman became an expert on photonics, laser and bioanalytical chemistry, chemical physics, catalysis, nano-materials and nano-devices. He was a professor at the University of Michigan for 57 years (1966-2023); the Richard Smalley Distinguished University Professor of Chemistry, Physics, Applied Physics, Biophysics, Biomedical Engineering and Chemical Biology; Member of The Michigan Nanotechnology Institute for Medicine and Biological Sciences, The Michigan Biointerfaces Institute, and The Rogel Cancer Center.

He mentored more than 70 PhD students in Biomedical Engineering, Chemistry, Physics, Biophysics and Applied Physics, who launched successful academic careers as professors at primary universities, or pursued excellence in industry and government. Professor Kopelman has been celebrated for his leadership, research, and educator role in the materials nanoscience community, for key developments in percolation theory applications and fractal kinetics, and for developing nanochemistry and nanobiochemistry scientific paradigms and tools, integrating these into nanomedicine to treat life-threatening diseases.

“Dr. Kopelman was a wonderful scientist and mentor,” said former student Ariel Hecht (BME, PhD, 2013). “I will always remember his love and enthusiasm for science — he was genuinely passionate for his work. He also fostered a lab environment where students were encouraged to independently explore ideas, and he was very supportive of trying new things; I personally benefited a lot from this approach. He focused on what was most important, provided me with great feedback and mentorship, and encouraged me to graduate and move on to the next step when the time was right. I am very grateful for having been in his lab for five years, and will miss him greatly.”

Former biomedical engineering student Irene Sinn (PhD, 2012) added: “In the wake of Professor Raoul Kopelman’s loss, we celebrate a unique individual who was more than a scientist; he was an exceptional mentor and friend,” she said. “I was honored to have Professor Kopelman as my co-advisor during my time at University of Michigan – he crafted my intellect and fostered my growth into a thoughtful scientist and empathetic person. The global scientific community, together with our UM family, mourns his departure but cherishes his profound influence. His legacy is not confined to his scholarly work; it echoes in his students and colleagues, in our values, and in the way we approach our respective fields. We honor his memory by perpetuating his dedication to science. Remembering Professor Kopelman, we recall his brilliance, honesty, and kindness that touched so many lives. His lasting impact in science and mentorship will inspire future generations.”

BME extends our condolences to Professor Kopelman’s family, friends, colleagues and former students on his loss.

‘IMAGING AND THERAPY IN VISION RESEARCH 2023’ COMING THIS WEEK

The BME Summer Workshop @ Michigan, titled “Imaging and Therapy in Vision Research 2023,” is happening August 11-12, 2023, at the NCRC Building 10, South Atrium.

This event, which is co-hosted by U-M BME and Ophthalmology and Visual Sciences, will provide a platform for discussing common research interests in diagnosis and treatment of pathologic conditions associated with the eye and the brain.

Featured guest speakers will include Dr. Joseph Izatt, the Michael J. Fitzpatrick Distinguished Professor of Engineering and Chair, Biomedical Engineering Department, Duke University; Dr. Xincheng Yao, the Richard and Loan Hill Professor from the University of Illinois at Chicago; Dr. Juliette E. McGregor, Assistant Professor at the University of Rochester, and Dr. Salavat Aglyamov, Research Assistant Professor from the University of Houston.

Here is the agenda for the event:

2-2:15 p.m. Opening Remarks

Mary-Ann Mycek, Interim Chair, Biomedical Engineering, Professor, Biomedical Engineering, University of Michigan

David Antonetti, Roger W. Kittendorf Research Professor of Ophthalmology and Visual Sciences, Professor, Ophthalmology and Visual Sciences, Professor, Molecular & Integrative Physiology, Scientific Director, Ophthalmology and Visual Sciences, University of Michigan

SESSION 1

Moderator: Guan Xu, Assistant Professor, Ophthalmology and Visual Sciences; Assistant Professor, Biomedical Engineering, University of Michigan

2:15-2:45 p.m.

Joseph Izatt, the Michael J. Fitzpatrick Distinguished Professor of Engineering, and Chair, Biomedical Engineering Department, Duke University: “New technologies for intra-operative and hand-held OCT” (joseph.izatt@duke.edu)

2:45-3 p.m.

Luis Hernandez-Garcia, Research Professor, Biomedical Engineering Research Professor, Functional MRI Laboratory: “Engineering Functional MRI at Michigan” (hernan@umich.edu)

3-3:15 p.m.

Mingyang Wang, PhD Student, U-M Biomedical Engineering: “Photo-mediated ultrasound therapy on the fundus of the eye—with real-time SD-OCT guidance” (mingyanw@umich.edu)

3:15-3:30 p.m.

Zhongming Liu, Associate Professor, Biomedical Engineering, Associate Professor, Electrical Engineering and Computer Science, U- M: “Imaging and decoding human visual cortex during natural vision” (zmliu@umich.edu)

3:30-3:45 p.m.

Valeria Caruso, Research Area Specialist Senior in the Kovelman Lab, U-M: “Shining Light on Child Brain Development: fNIRS studies of child language, literacy, and cognition” (vcaruso@umich.edu)

3:45-4 p.m.

Zhen Xu, Professor, Biomedical Engineering, U-M: “Transcranial histotripsy for neurological applications” (zhenx@umich.edu)

4-4:30 p.m. Break

SESSION 2

Moderator: Xueding Wang, Jonathan Rubin Collegiate Professor, Biomedical Engineering; Professor, Radiology, University of Michigan

4:30-5 p.m.

Xincheng Yao, the Richard and Loan Hill Professor, University of Illinois at Chicago: Wide field fundus photography (xcy@uic.edu)

5-5:15 p.m.

Mark Draelos, Assistant Professor, Robotics, Assistant Professor, Ophthalmology and Visual Sciences, U-M: “Robotic OCT for Unstabilized Ophthalmic Imaging” (mdraelos@umich.edu)

5:15-5:30 p.m.

Van Phuc Nguyen, Postdoctoral Research Fellow, Paulus Lab, U-M: “Molecular and Cellular Imaging of the Retina” (vanphucn@med.umich.edu)

5:30-5:45 p.m.

Dongshan Yang, Research Assistant Professor, Internal Medicine, Medical School, U-M: “Genetically Engineered Rabbit Models of Inherited Retinal Disease” (doyang@med.umich.edu)

5:45-6 p.m.

Hao Su, Associate Professor, Department of Mechanical and Aerospace Engineering; Director, Lab of Biomechatronics and Intelligent Robotics, North Carolina State University: “Design, Learning, and Control for Snake-like Robotic Microsurgery” (hao.su796@ncsu.edu)

6-6:15 p.m.

Yannis Paulus, Helmut F Stern Career Development Professor, Associate Professor of Ophthalmology and Visual Sciences, Associate Professor of Biomedical Engineering and Medical Director, Grand Blanc Ophthalmology, Medical School: “Biodegradable silicon nanoneedles for sustained treatment of ocular angiogenesis” (ypaulus@med.umich.edu)

6:15-6:30 p.m.

Kwoon Wong, Associate Professor, Ophthalmology and Visual Sciences Associate Professor, Molecular, Cellular & Developmental Biology, & Guan Xu, Assistant Professor, Ophthalmology and Visual Sciences, Assistant Professor, Biomedical Engineering: “Imaging Visually-Evoked Hemodynamic Responses in the Mouse Brain Using Photoacoustic Computed Tomography” (kwoon@umich.edu, guanx@umich.edu)

Dinner Reception 6:30-8:30 p.m.

Saturday, August 12

SESSION 3

Moderator: Jim Weiland, Associate Chair for Research, Biomedical Engineering;

Professor, Biomedical Engineering; Professor, Ophthalmology and Visual Sciences, University of Michigan

8:30-9 a.m.

Salavat Aglyamov, Research Assistant Professor from the University of Houston: “Elastography of ocular tissues using optical methods” (saglyamo@Central.UH.EDU)

9-9:15 a.m.

Linyu Ni, PhD Student, U-M Biomedical Engineering: “Role of aqueous veins and perilimbal sclera in the regulation of intra ocular pressure” (nilinyu@umich.edu)

9:15-9:30 a.m.

Yanhui Ma, Research Scientist, The Ohio State University: “Retinal Biomarkers of Hypertensive Effects on Cognitive Function” (ma.1634@osu.edu)

9:30-9:45 a.m.

Tianqu Zhai, PhD Candidate, U-M: “Multi-modality Imaging of Retinal and

Cerebral Biomarkers in Mice with Alzheimer’s Disease” (tianquzh@umich.edu)

9:45-10 a.m.

Kevin Chang, PhD Candidate, Biomedical Engineering, U-M: “Photoacoustic Imaging of Hemodynamic Responses in Squirrel Monkey Brain Induced by Peripheral Electrical and Mechanical Stimulation” (kaiweic@umich.edu)

10-10:30 a.m. Break

SESSION 4

Moderator: Yannis Paulus, Helmut F Stern Career Development Professor, Associate Professor, Ophthalmology and Visual Sciences; Associate Professor, Biomedical Engineering, University of Michigan

10:30-11 a.m.

Juliette McGregor, Assistant Professor at the University of Rochester: “Advancing vision restoration therapies using calcium imaging ophthalmoscopy”

(jmcgrego@ur.rochester.edu)

11-11:15 a.m.

Jim Weiland, Associate Chair for Research in Biomedical Engineering (Medical School), Professor, Biomedical Engineering, Professor, Ophthalmology and Visual Sciences, U-M: “Calcium Imaging of Electrically Elicited Responses in the Retina” (weiland@med.umich.edu)

11:15-11:30 a.m.

Yujia Hu, Research Investigator, Life Sciences Institute, Ye Lab (Bing group): “LabGym 2: versatile and efficient automated analysis of complex behaviors” (henryhu@umich.edu)

11:30-11:45 a.m.

Maria do Carmo Pereira da Costa, Research Assistant Professor, Neurology: “Altered retinal structure and function in Spinocerebellar ataxia type 3” (mariadoc@med.umich.edu)

11:45-Noon

Ye Li, Research Fellow, Cai Lab (Dawen group): “Novel transgenic tools for studying the functional connectome of the Drosophila visual projection circuitry” (cnliye@umich.edu)

Noon-12:30 p.m. Box Lunch

Thank you to our special guest speakers:

Salavat Aglyamov, Research Assistant Professor, University of Houston

Joseph Izatt, the Michael J. Fitzpatrick Distinguished Professor of Engineering, and Chair of Biomedical Engineering, Duke University

Juliette E. McGregor, Assistant Professor, University of Rochester

Xincheng Yao, the Richard and Loan Hill Professor, University of Illinois at Chicago

New kind of superresolution explores cell division

by Kate McAlpine

A new way to see details smaller than half the wavelength of light has revealed how nanoscale scaffolding inside cells bridges to the macroscale during cell division. Unlike earlier superresolution techniques, the one developed and tested at the University of Michigan doesn’t rely on molecules that wear out with prolonged use.

Superresolution can reveal structures down to 10 nanometers, or about the same breadth as 100 atoms. It opened a whole new world in biology, and the techniques that first made it possible received a Nobel Prize in 2014. However, its weakness has been that it can only take snapshots over tens of seconds. This makes it impossible to observe the evolution of the machinery of a cell over long periods of time.

“We were wondering—when the system as a whole is dividing, how do nanometer-scale structures interact with their neighbors at the nanometer scale, and how does this interaction scale up to the whole cell?” said Somin Lee, an assistant professor of electrical and computer engineering at U-M, who led the study in Nature Communications. Co-authors of the study include BME Professor David Sept and BME PhD student Di Zu.

To answer that question, they needed a new kind of superresolution. Using their new method, they were able to continuously monitor a cell for 250 hours.

“The living cell is a busy place with proteins bustling here and there. Our superresolution is very attractive for viewing these dynamic activities,” said Guangjie Cui, a PhD student in electrical and computer engineering and co-first author of the study with Yunbo Liu, a PhD graduate in electrical and computer engineering.

Like the original method, the new technique uses probes near the nanoscale objects of interest to shed light on them. Superresolution 1.0 used fluorophores for this, fluorescent molecules that would send out an answering light after being illuminated. If the fluorophores were closer together than the size of whatever was being imaged, the image could be reconstructed from the bursts of light produced by the fluorophores.

The new technique uses gold nanorods, which don’t break down with repeated exposure to light, but making use of the light that interacts with them is more challenging. Nanorods respond to the phase of the light, or where it is in the up-and-down oscillation of the electric and magnetic fields that compose it. This interaction depends on how the nanorod is angled to the incoming light.

Like the fluorophores, the nanorods can attach to particular cell structures with targeting molecules on their surfaces. In this case, the nanorods sought out actin, a protein that adds structure to soft cells. Actin is shaped like branching filaments, each about 7 nanometers (millionths of a millimeter) in diameter, though they link together to span thousands of nanometers. Even though the nanorods are often more than twice the diameter of the actin, the data they provide as a group can illuminate its tiny details.

To locate the nanorods, the team built filters made of thin layers of polymers and liquid crystals. These filters enabled the detection of light with a particular phase, enabling the team to pick out nanorods with particular angles to the incoming light. By taking 10-30 images—each looking at a different subset of nanorods—and merging them into a single image, the team was able to deduce the nanometer-scale details of the filaments inside the cells. These details would be blurred out in conventional microscopes.

Using the technique, the team discovered three rules governing the way that actin self-organizes during cell division:

Actin expands to reach its neighbors when actin filaments are far apart.
Actin will draw nearer to its neighbors to increase connections, although this tendency is tempered by the drive to expand and reach more neighbors.
As a result, the actin network tends to contract when it is more connected, and it will expand when it is less connected.

The behavior of the actin is connected to the behavior of the cell—but the cell contracts when the actin expands, and it expands when the actin contracts. The team wants to explore this further, discovering why the motions are opposite at different scales. They also want to investigate the consequences of dysregulating this molecular process: Is this at the root of some diseases?

More broadly, they hope to use superresolution to understand how self-organization is built into biological structures, without the need for central control.

“Our genetic code doesn’t actually include enough information to encode every detail of the organization process. We want to explore the mechanisms of collective behaviors without central coordination that are like birds flying in formation—in which the system is driven by interactions between individual parts,” said Lee.

The study was supported by the Air Force Office of Scientific Research, grant nos. FA9550-16-1-0272, FA9550-19-1-0186, and FA9550-22-1-0285; and the National Science Foundation grant no. 1454188.

Study: Phase intensity nanoscope (PINE) opens long-time investigation windows of living matter (DOI: 10.1038/s41467-023-39624-w)

BME Faculty, Research Staff Honored With 2023 EBS Awards

Sriram Chandrasekaran, Assistant Professor, U-M Biomedical Engineering, is a 2023 recipient of the (EBS) Endowment for the Basic Sciences 2023 Teaching Award, representing U-M Biomedical Engineering. Chandrasekaran was acknowledged for his instruction in the Artificial Intelligence in Biomedical Engineering course, which has been taught since 2020 (BME 499/487).

“This course is open to both graduates and undergraduate students,” he said. ‘We focus on practical applications of AI in Biomedicine, with hands-on programming tutorials. This course provides an overview of a wide range of AI tools, biomedical data sets (imaging, omics, health records) and diseases (cancer, cardiovascular-, infectious- and brain diseases). It has attracted a diverse pool of students, and course evaluations have been excellent.”

Congratulations also to Mackenzie Moore, who received the EBS Research Staff Award. Moore manages multiple, complex projects in Prof. Tim Bruns’ research group. Throughout her time in his laboratory, Moore has exceeded his expectations.

As Prof. Bruns writes, “Mackenzie has maintained her positive, can-do attitude” and is an “exemplary representative of Biomedical Engineering and the University of Michigan.”

The EBS is a cooperative program developed by former Medical School Dean, Allen Lichter, and the Chairs and Directors of the participating units. Together, they work for the advancement of research and teaching in the Medical School Basic Sciences through the development of new research initiatives and recruitment of new faculty.

Chandrasekaran also received the 2022 EBS Accelerator Award last year to serve as a catalyst for his research activities and in recognition for his many contributions to U-M Biomedical Engineering, especially in the area of antibiotic discovery using mechanistic artificial intelligence.

Antibiotic resistant bacteria are considered to be one of the biggest threats to humanity by WHO. Pathogens are becoming progressively drug resistant, yet drug discovery methods have failed to produce new classes of antimicrobials for decades. There is an urgent need to identify effective therapies from existing FDA approved drugs. Using a unique combination of metabolic modeling, multi-omics data and machine learning algorithms, Chandrasekaran’s laboratory will create a new tool for discovering new therapies and also investigate the biochemical principles that govern drug mechanisms of action. His approach will significantly reduce the time and cost of drug development. There are currently no theoretical models that can integrate biochemical, molecular, metabolic and drug toxicity data to guide drug design. His study is necessary to address an important void in drug discovery.

BME Student Receives 2023-2024 J. Robert Beyster Computational Innovation Graduate Fellowship

U-M BME PhD student Lauren Madden will receive the 2023-2024 J. Robert Beyster Computational Innovation Graduate Fellowship from the College of Engineering.

This fellowship is for domestic Ph.D. graduate students in the College of Engineering who have reached candidacy to support cutting-edge research in a variety of fields linking high performance computing, networking, and storage to applications of societal importance in the following areas, but not limited to:

–Bioinformatics (including genomics and modeling/study of the brain)

–Computer and Network Security (including mobile computing and the cloud)

–Computational Materials (including renewable energy and biological materials)

–Computational Electromagnetics (including imaging and stealth technology)

–Autonomous Systems (including automotive safety and military air, land, sea, and underwater vehicles)

–Multi-Physics Simulation (including radiation and thermal transport and reactor safety)

BME Faculty Receive 2023 MICHR Distinguished Clinical and Translational Research Mentor Award

Congratulations to two U-M BME faculty members who have received the 2023 MICHR Distinguished Clinical and Translational Research Mentor Award.

Mario L. Fabiilli, Associate Professor of Radiology, Medical School; Associate Professor of Biomedical Engineering, College of Engineering and Medical School; and Lonnie Shea, Steven A. Goldstein Collegiate Professor of Biomedical Engineering, College of Engineering and Medical School; Professor of Chemical Engineering, College of Engineering; and Professor of Surgery, Medical School, are among the seven recipients this year.

The Michigan Institute for Clinical & Health Research (MICHR) has selected individuals who meet the highest standard for clinical and translational research mentorship. The pool of nominees represents a diverse group of U-M units, including Engineering, the Institute for Survey Research, Literature, Science & the Arts, Medicine, Nursing, Public Health, and the University of Michigan Flint.

Toward a stem cell model of human nervous system development Human cells could one day show us more about why neural tube birth defects occur and how to prevent them.

Human embryonic stem cells can be guided to become the precursor tissue of the central nervous system, research led by the University of Michigan has demonstrated. The new study also reveals the important role of mechanical signals in the development of the human nervous system.

While studying embryonic development using animal embryos can provide useful insights about what happens during human development, human embryos grow differently even at this early stage.

“There is a critical need to establish embryonic developmental models using human cells. Not only could they advance our fundamental understanding of human development, they are also essential for regenerative medicine and for testing the safety of drugs and chemicals that pregnant women may need or encounter,” said Jianping Fu, an associate professor of mechanical engineering, who has been supervising this research.

“For the first time, we are able to use human embryonic stem cells to develop a synthetic model of neuroectoderm patterning, the embryonic event that begins the formation of the brain and spinal cord in the human embryo.”

There is a critical need to establish embryonic developmental models using human cells.Jianping Fu, associate professor of mechanical engineering.

In humans, the cells that will later differentiate into the central nervous system (including the brain and spinal cord) are known as the neural plate, while those that stand between the neural plate and future skin cells are called the neural plate border. The neural plate folds in on itself about 28 days after conception, becoming the neural tube, and the border on either side of it fuses together along its length. When the neural tube fails to close properly, it typically results in paralysis or death.

“The exact causes of neural tube defects are not clear, and there is currently no cure for them. Environmental factors, such as certain drugs pregnant women take, may play roles in causing neural tube defects,” said Fu.

In the new study, Fu’s research team arranged human embryonic stem cells into circular cell colonies with defined shapes and sizes. The cells were then exposed to chemicals known to coax them to differentiate into neural cells. During the differentiation process, cells in circular colonies organized themselves with neural plate cells in the middle and neural plate border cells in a ring around the outside.

“Since all of the cells in a micropatterned colony are in the same chemical environment, it’s amazing to see the cells autonomously differentiate into different cells and organize themselves into a multicellular pattern that mimics human development,” said Xufeng Xue, a PhD student in mechanical engineering working in Fu’s research group. Xue is a co-first author of the paper.

Disc-shaped colonies shown with phase contrast (top) and fluorescence (bottom) microscopy. Between day 3 and day 9, cells in the center of the colony grow faster and become much more densely packed. Confined space drives the cells in the center of the colony to become neural plate cells, whereas those cells at the colony border (experiencing less confinement) differentiate into neural plate border cells. Image: Xufeng Xue, Integrated Biosystems and Biomechanics Laboratory, University of Michigan.

Fu’s team observed that cells in the circular colony became more densely packed in the middle of the colony, where they became neural plate cells, versus the colony border, where they became neural plate border cells. Suspecting mechanical signals might affect their differentiation, they placed single human embryonic stem cells onto adhesive spots of different sizes.

In the same chemical environment, single human embryonic stem cells grown on larger spots began signaling events within the cells that drove them toward becoming neural plate border cells. These signaling events were inhibited in stem cells confined on smaller spots. The team also developed a system to stretch cells in the middle of a colony. Responding to this mechanical signal, the cells in the middle of a colony differentiated into neural plate border cells, rather than the neural plate cells at the center of an ordinary colony.

“While many current models attribute patterning of embryonic tissues to chemical gradients or cell migration, our results show that these factors may not be the only drivers,” said Yubing Sun (ME PhD ’15), a former doctoral student in Fu’s lab and now an assistant professor of mechanical and industrial engineering at the University of Massachusetts, Amherst. Sun is a co-first author of the paper.

The study, titled, “Mechanics-guided embryonic patterning of neuroectoderm tissue from human pluripotent stem cells,” is published in Nature Materials.

This work was supported by the National Science Foundation (grant numbers CMMI 1129611, CBET 1149401and CMMI 1662835), the American Heart Association (grant number 12SDG12180025) and the U-M Department of Mechanical Engineering.

Fu is also an associate professor of biomedical engineering, cell and developmental biology, and is an associate director of the Michigan Center for Integrative Research in Critical Care.

Credits:

By Kate McAlpine, Senior Writer & Assistant News Editor, (734) 763-4386
Paper abstract: https://www.nature.com/articles/s41563-018-0082-9
Original article: https://news.engin.umich.edu/2018/05/toward-a-stem-cell-model-of-human-nervous-system-development/

Findings in mice show pill for breast cancer diagnosis may outperform mammograms A new kind of imaging could distinguish aggressive tumors from benign, preventing unnecessary breast cancer treatments.

As many as one in three women treated for breast cancer undergo unnecessary procedures, but a new method for diagnosing it could do a better job distinguishing between benign and aggressive tumors. Researchers at the University of Michigan are developing a pill that makes tumors light up when exposed to infrared light, and they have demonstrated that the concept works in mice.

Mammography is an imprecise tool. About a third of breast cancer patients treated with surgery or chemotherapy have tumors that are benign or so slow-growing that they would never have become life-threatening, according to a study out of Denmark last year. In other women, dense breast tissue hides the presence of lumps and results in deaths from treatable cancers. All that, and mammograms are notoriously uncomfortable.

“We overspend $4 billion per year on the diagnosis and treatment of cancers that women would never die from,” said Greg Thurber, an assistant professor of chemical engineering and biomedical engineering, who led the team. “If we go to molecular imaging, we can see which tumors need to be treated.”

The move could also catch cancers that would have gone undetected. Thurber’s team uses a dye that responds to infrared light to tag a molecule commonly found on tumor cells, in the blood vessels that feed tumors and in inflamed tissue. By providing specific information on the types of molecules on the surface of the tumor cells, physicians can better distinguish a malignant cancer from a benign tumor.

Compared to visible light, infrared light penetrates the body easily—it can get to all depths of the breast without an X-ray’s tiny risk of disrupting DNA and seeding a new tumor. Using a dye delivered orally rather than directly into a vein also improves the safety of screening, as a few patients in 10,000 can have severe reactions to intravenous dyes. These small risks turn out to be significant when tens of millions of women are screened every year in the US alone.

But it’s not easy to design a pill that can carry the dye to the tumor.

“To get a molecule absorbed into the bloodstream, it needs to be small and greasy. But an imaging agent needs to be larger and water-soluble. So you need exact opposite properties,” said Thurber.

Fortunately, they weren’t the only people looking for a molecule that could get from the digestive system to a tumor. The pharmaceutical company Merck was working on a new treatment for cancer and related diseases. They got as far as phase II clinical trials demonstrating its safety, but unfortunately, it wasn’t effective.

“It’s actually based on a failed drug,” said Thurber. “It binds to the target, but it doesn’t do anything, which makes it perfect for imaging.”

The targeting molecule has already been shown to make it through the stomach unscathed, and the liver also gives it a pass, so it can travel through the bloodstream. The team attached a molecule that fluoresces when it is struck with infrared light to this drug. Then, they gave the drug to mice that had breast cancer, and they saw the tumors light up.

“It’s actually based on a failed drug. It binds to the target, but it doesn’t do anything, which makes it perfect for imaging.”Greg Thurber

The research is described in a paper in the journal Molecular Pharmaceutics, titled, “Oral administration and detection of a near-infrared molecular imaging agent in an orthotopic mouse model for breast cancer screening.”

This work was done in collaboration with David Smith, the John G. Wagner Collegiate Professor of Pharmaceutical Sciences in the College of Pharmacy, and a member of the Comprehensive Cancer Center.

The study was supported by the Foundation for Studying and Combating Cancer and the National Institutes of Health.

Credits:

By Kate McAlpine, Senior Writer & Assistant News Editor, (734) 763-4386
Original article: https://news.engin.umich.edu/2018/04/pill-for-breast-cancer-diagnosis-may-outperform-mammograms/

‘Nightmare bacteria:’ Michigan Engineers discuss how to combat antibiotic resistance Drug-resistant bugs are on the rise and new approaches are needed.

Health officials at the U.S. Centers for Disease Control and Prevention earlier this month said they are seeing rising cases of “nightmare bacteria” that show strong resistance to antibiotics. More than 200 cases were reported in the last year alone, and across every state in the U.S.

“Unusual resistance germs—which are resistant to all or most antibiotics tested and are uncommon or carry special resistance genes—are constantly developing and spreading,” the CDC said.

A particular concern is the number of cases that crop up in hospitals and nursing homes where IVs, catheters and medical implants—all particularly susceptible to infection—are common.

“Antibiotic resistance is one of the most important public health problems of the 21st century,” said Angela Violi, professor of mechanical engineering and chemical engineering at U-M.

Violi is one of many researchers at Michigan Engineering who are are tackling this issue from a variety of angles. Some are exploring new ways to combine antibiotics to stay one step ahead of the bugs. Others are looking beyond antibiotics—to nanoparticles.

Nicholas Kotov, the Joseph B. and Florence V. Celka professor of chemical engineering, is part of a team researching the use of nanoparticles as a new form of antibiotics. Nanoparticles can be shaped specifically to get past a bacterium’s defenses and shut down processes essential to its survival. Nanoparticles can also be used to coat medical implants in order to prevent infection from drug resistant bacteria.

“New methods of suppressing or otherwise diminishing the health impact of antibiotic resistant bacteria are needed,” Kotov said. “Molecular and nanoscale engineering of inorganic nanoparticles offers this opportunity by utilizing the latest experimental and computational tools targeting the bacteria where it does not expect.”

Violi helps identify the best pathways for utilizing nanoparticles to attack antibiotic resistant bacteria.

“Potentially, all it takes is a single mutated bacterium to render an antibiotic useless for that infection,” she said. “When that mutant cell replicates, it will pass on its resistant phenotype to its daughter cells, and so on.

“At that point part of the replicating bacteria will be drug resistant: the drug will kill only those cells that do not have the newly evolved drug-resistance capacity. Eventually, the entire bacterial population will become resistant to the prescribed antibiotic.

“It is only when antibiotics are used that drug-resistant phenotypes have a selective advantage and survive.

“Nano and chemical engineering approaches provide unparalleled flexibility to control the composition, size, shape, surface chemistry, and functionality of nanostructures that can be used to develop a new generation of modified materials or to coat existing solid surfaces to fight bacteria.”

Professor working on a computer in the lab — Sriram Chandrasekaran, an assistant professor of biomedical engineering, uses computer simulations to develop strategies for using current antibiotics in combination as well as roadmaps for creating new classes of antibiotics. Photo by Joseph Xu

Sriram Chandrasekaran, an assistant professor of biomedical engineering, approaches drug resistant bacteria from a different angle. He and his team study proteins and analyze their behaviors via computer simulations to develop strategies for using current antibiotics in combination as well as roadmaps for creating new classes of antibiotics.

“In addition to better stewardship of antibiotics, we also need to come up with smarter treatment strategies that can reduce the rise of resistance,” Chandrasekaran said.

“For example, our lab and others are designing combinations of antibiotics that are more effective in retarding the evolution of drug resistance compared to using drugs individually. Such combinations of FDA approved drugs can also reach the clinic faster than developing new drugs from scratch.

“We are also developing computer algorithms that can identify the most optimal combination of drugs for a specific strain of pathogen. Overall, what we can learn from this crisis is that we cannot take antibiotics for granted. We have to keep investing on new treatments as bacteria will always eventually evolve resistance to whatever new drug we throw at it.”

Credits:

By James Lynch, Michigan Engineering, Research News & Feature Writer, (734) 763-1652
Original article: https://news.engin.umich.edu/2018/04/nightmare-bacteria-michigan-engineers-discuss-how-to-combat-antibiotic-resistance/

No sponge left behind: tags for surgical equipment A simple, easy-to-implement technology could prevent the debilitating injuries that can occur when organs are damaged by surgical tools left in the body.

Items left behind in patients after surgery can have an enormous personal cost when organs and tissues are damaged. Surgical sponges are among the worst offenders – difficult to see in post-surgical X-rays and yet capable of causing holes when the intestines grow around them, for example. These rare cases, estimated around one in 3,000 surgeries that carry a risk, add up to around $1.5 billion in costs per year.

X-ray image showing scissors inside a cadaver — Marentis took about 2,800 X-ray images of the tag to train and test the software.

The current method of accounting for surgical tools involves counting them before and after surgery and performing an X-ray if there’s a mismatch. Without the metal bands inside them, the gauze sponges wouldn’t appear at all, but they are still difficult to see. A new, unmistakeable tag could change that – and its signature is so clear that computers can also detect it.

The tag, which is about the same size and shape as an acetaminophen tablet, contains four metal spheres, arranged at the points of a tetrahedron. This simple shape can be recognized by the computer no matter how it is turned. With human radiologists having a first look at the X-rays and then comparing their findings with a computer, over 98 percent of the tags can be seen. In contrast, as many as half of surgical sponges are missed in X-rays today.

The research team has formed the company Kalyspo, and they are building partnerships with surgical sponge manufacturers and hospitals in an effort to make the tag and software a standard part of surgical procedures, keeping patients safer.

Nikolaos Chronis, an associate professor of mechanical engineering at U-M, led the development of the tag. Theodore Marentis, then a radiology resident at U-M, identified the need for such a tag and worked with Chronis to develop and test it. Lubomir Hadjiyski, a professor of radiology at U-M, led the development of the software that locates the tags.

Chronis is also an associate professor of biomedical engineering and macromolecular science and engineering. Marentis is now a radiologist at the Mercy Medical Center in Mt. Shasta, CA.

Credits:

By Kate McAlpine
Original article: https://news.engin.umich.edu/2018/03/no-sponge-left-behind-tags-for-surgical-equipment/

Closest look yet at killer T-cell activity could yield new approach to tackling antibiotic resistance An in-depth look at the work of T-cells, the body's bacteria killers, could provide a roadmap to effective drug treatments.

In a study that could provide a roadmap for combatting the rising threat of drug-resistant pathogens, researchers have discovered the specific mechanism the body’s T-Cells use to kill bacteria.

University of Michigan researchers, in collaboration with colleagues at Harvard University, have discovered a key difference between the way immune cells attack bacteria and the way antibiotics do. Where drugs typically attack a single process within bacteria, T-Cells attack a host of processes at the same time.

On Thursday, the journal Cell published findings from a team headed by U-M’s Sriram Chandrasekaran and Harvard’s Judy Lieberman. It’s a study with potential implications for drug-resistant pathogens—a problem projected to kill as many as 10 million people annually across the globe by the year 2050.

“We have a huge crisis of antibiotic resistance right now in that most drugs that treat diseases like tuberculosis or listeria, or pathogens like E.coli, are not effective,” said Chandrasekaran, an assistant professor of biomedical engineering. “So there is a huge need for figuring out how the immune system does its work. We hope to design a drug that goes after bacteria in a similar way.”

We’ve reached a point where we take what antibiotics can do for granted, and we can’t do that anymore.Sriram Chandrasekaran

Killer T-Cells, formally known as cytotoxic lymphocytes, attack infected cells by producing the enzyme granzyme B. How this enzyme triggers death in bacteria has not been well understood, Chandrasekaran said.

Proteomics – a technique that measures protein levels in a cell—and computer modeling, allowed researchers to see granzyme B’s multi-pronged attack targeting multiple processes.

Chandrasekaran and his team monitored how T-Cells deal with three different threats: E. coli, listeria and tuberculosis.

“When exposed to granzyme B, the bacteria were unable to develop resistance to the multi-pronged attack, even after exposure over multiple generations,” Chandrasekaran said. “This enzyme breaks down multiple proteins that are essential for the bacteria to survive.

“It’s essentially killing several birds with one stone.”

The possible applications of the new findings on T-Cells run the gamut from the creation of new medications to the re-purposing of previously-approved drugs in combination to fight infections by mimicking granzyme B.

Chandrasekaran’s team is now looking at how bacteria hide to avoid T-Cell attacks.

And the need for a new approach in some form is dire. World Health Organization officials describe antibiotic resistance as “one of the biggest threats to global health, food security and development today.”

Sriram Chandrasekaran, Assistant Professor of Biomedical Engineering, shows a computer model of a pathway for a potential disease or infection. Photo: Joseph Xu

Each year, an estimated 700,000 deaths are linked to antibiotic-resistant bacteria, according to the World Health Organization. Projections show that number skyrocketing to 10 million by 2050.

England’s top health official, Sally Davies, recently said the lost effectiveness of antibiotics would mean “the end of modern medicine.”

“We really are facing—if we don’t take action now—a dreadful post-antibiotic apocalypse,” she was quoted saying earlier this month. “I don’t want to say to my children that I didn’t do my best to protect them and their children.”

Of particular concern is the fact that there are few new antibiotics in the pipeline. The heyday of new antibiotics occurred the 1940s through the 1960s, with releases eventually grinding almost to a halt by the end of the twentieth century.

“We’ve reached a point where we take what antibiotics can do for granted, and we can’t do that anymore,” Chandrasekaran said. “We’re taking inspiration from the human immune system, which has been fighting infections for thousands of years.”

The paper is titled, “Granzyme B disrupts central metabolism and protein synthesis in bacteria to promote an immune cell death program.” The research is funded by the National Institutes of Health, Harvard University and the University of Michigan.

Credits:

by James Lynch, Research News & Feature Writer, Michigan Engineering
Original Article: https://news.engin.umich.edu/2017/10/tackling-antibiotic-resistance/
Paper in Cell: http://www.cell.com/cell/fulltext/S0092-8674(17)31188-1
Header Image Caption: Sriram Chandrasekaran, Assistant Professor of Biomedical Engineering, shows a computer model of a pathway for a potential disease or infection. Photo: Joseph Xu

Bionic heart tissue: U-Michigan part of $20M center Scar tissue left over from heart attacks creates dead zones that don’t beat. Bioengineered patches could fix that.

The University of Michigan is partnering on an ambitious $20 million project to grow new heart tissue for cardiac patients. The new research center has been awarded to Boston University (BU), with strong partnership from U-M and Florida International University (FIU).

“A heart attack creates scar tissue, and the heart never returns to full function. But for every person, we could create a living patch that a surgeon could stitch in,” said Stephen Forrest, who leads the nanotechnology aspect of the project and is U-M’s Peter A. Franken Distinguished University Professor of Engineering. “It’s very audacious.”

The project is a National Science Foundation Engineering Research Center. These 5-year grants are typically renewed for another 5 years, so the researchers are looking at a 10-year timeline to go from the current state of tissue engineering to working, implantable heart tissue.

A heart attack creates scar tissue, but we could create a living patch that a surgeon could stitch in.Steve Forrest

“Heart disease is one of the biggest problems we face,” said David Bishop, director of the new center and a BU professor of electrical and computer engineering and physics. “This grant gives us the opportunity to define a societal problem, and then create the industry to solve it.”

The living patches the researchers are developing would consist of heart muscle cells, blood vessels to carry nutrients in and waste out, and optical circuitry to make the heart muscle cells beat in synchrony. Already, researchers in the lab have been developing ways to structure cells in scaffolds that mimic particular organs and grow blood vessels into artificial tissues. But typically, working implants have been static, biodegradable materials such as artificial windpipes that the body gradually replaces with tissue. Working tissue, like heart muscle, would need to be responsive as soon as it was implanted.

Engineering Research Center grants are extremely competitive, with only four of more than 200 applicants receiving an award in 2017. These centers are designed to work directly with industry to translate breakthroughs along the way out of the lab and into healthcare. Just producing a more true-to-life “heart on a chip” could aid the pharmaceutical industry in developing better treatments for problems such as arrhythmia.

Ramcharan and her colleagues in Lahann’s lab will help design and produce a polymer-protein construct that mimics the 3D matrix connecting the cells in human heart muscle. Heart muscle cells moving into this environment will then be able to link up into a single tissue. Photo: Joseph Xu, Michigan Engineering Communications & Marketing.

In order to produce the heart tissue, the team intends to start with an artificial scaffold that mimics the 3D structure of heart tissue. Joerg Lahann, a U-M professor of chemical engineering, will work with the team building the flexible polymer scaffold, as well as on the attachment and monitoring of cells within that framework.

“Michigan is pleased to lend expertise to the development of implantable heart tissue, which could improve and extend so many lives,” said Alec D. Gallimore, the Robert J. Vlasic Dean of Engineering. “Our faculty members are leaders in nanotechnology and in developing materials that support and interact with living cells and tissues, two areas that are critical to the project’s success.”

The 3D scaffold will initially be peppered with nanometer-sized gold patches that act as attachment points for protein fragments, called peptides, which will then serve as anchors for the cells. They will be printed onto the gold patches using a technique developed by Forrest and Max Shtein, a U-M associate professor of materials science and engineering. This method, called organic vapor jet printing, was initially invented for mass-producing electronic devices.

“The adaptation of this technology to biological systems represents a radically new step,” said Forrest. U-M will receive $2.8 million for these contributions.

Christopher Chen, the center’s director of cellular engineering and a BU professor of biomedical engineering, will lead the effort to grow heart muscle cells on the scaffold and infuse the tissue with blood vessels. Meanwhile, Alice White, director of nanomechanics and chair of the BU mechanical engineering department will work closely with Arvind Agarwal, an FIU professor of mechanical and materials engineering, to produce an artificial nervous system that uses light to synchronize the heartbeat in the tissue.

Stacy Ramcharan, a doctoral student in chemical engineering, uses a computerized system to layer polymer fibers, forming a scaffold for growing cells into artificial tissues. Photo: Joseph Xu, Michigan Engineering Communications & Marketing.

“It’s humbling to have the opportunity to work on something that could really be a game changer,” says Bishop. “If we succeed, we’ll save a lot of lives and add meaningful years for many people.”

In addition to the technical thrusts led by Forrest, Chen and White, Thomas Bifano, a professor of mechanical engineering and director of BU’s Photonics Center, will direct imaging.

Along with the core partners, Harvard Medical School, Columbia University, the Wyss Institute at Harvard, Argonne National Laboratory, the École Polytechnique Fédérale de Lausanne in Switzerland, and the Centro Atómico in Argentina will offer expertise in bioengineering, nanotechnology, and other areas.

Forrest is also the Paul G. Goebel Professor of Engineering, and a professor of electrical engineering and computer science, material science and engineering, and physics. Lahann is also a professor of material science and engineering, biomedical engineering, and macromolecular science and engineering. Shtein is also an associate professor of chemical engineering, macromolecular science and engineering, and art and design. Gallimore is also the Richard F. and Eleanor A. Towner Professor, an Arthur F. Thurnau Professor, and a professor of aerospace engineering.

Credits:

by Kate McAlpine, Senior Writer & Assistant News Editor, Michigan Engineering
Original Article: https://news.engin.umich.edu/2017/09/bionic-heart-tissue-u-michigan-part-of-20m-center/
Header Image Caption: Scar tissue left behind after a heart attack can’t beat again, but bionic heart muscle patches, the goal of a new $20M center, could pick up the slack. Courtesy Getty Images.