January 6, 2017
On January 2, 2017, five new faculty started at U-M Biomedical Engineering. Each brings their own expertise in diverse areas, adding to U-M BME's many strengths.
Carlos Andres Aguilar
Carlos Andres Aguilar joins BME in January. He will use his background in muscle stem cell biology, epigenetic regulation, and micro/nanofabricated devices to develop tools to understand and engineer muscle function. By generating insights into the basic processes of muscle cells (development, differentiation, fusion, cell-communication, responses to stimuli), his lab hopes to set the stage for not only enhanced muscle performance but the treatment of conditions from muscular dystrophy to severe trauma and aging.
Aguilar completed his PhD in BME at the University of Texas at Austin then joined MIT Lincoln Laboratory’s Bioengineering Systems and Technology Group, where he learned to generate and analyze integrative genomic datasets. Working with collaborators from Harvard, the Broad Institute, and the U.S. Army Institutes of Surgical Research and Environmental Medicine, Aguilar began to develop programs using these sequencing-based tools to investigate the molecular mechanisms regulating muscle healing after trauma. Ultimately, such insights could guide the development of quantitative diagnostics and therapies.
Aguilar plans to continue his work on integrative genomic assays, high-throughput sequencing, and regenerative medicine at Michigan, further expanding into the study of single cells, cellular transplants, and genome editing. In addition to understanding muscle stem cell biology and regeneration, he is interested in rehabilitation, cellular reprogramming and cell-fate plasticity, including transcriptional and epigenetic factors, microenvironment interactions, and chromatin memory. He will also focus on micro/nanodevices for interacting with and manipulating single cells and molecules.
“Since graduating from Michigan, it’s been a dream to come back and mentor the next generation of students in the way I was taught,” says Aguilar. “The school has the ideal mix for an interdisciplinary person such as myself – from a strong computational biology department for interpreting the high-throughput sequencing datasets we’ll generate to clinicians and translational scientists who focus on muscle and regenerative medicine – as well as excellent micro/nanofabrication facilities.”
Students with a background in molecular biology, bioinformatics/data analysis, and micro/nanodevice fabrication can contact firstname.lastname@example.org about working in his lab.
Multi-Scale Systems Biology
Sriram Chandrasekaran’s Systems Biology Lab develops computer models of biological processes to understand them holistically. He is interested in deciphering how thousands of proteins work together at the microscopic level to orchestrate complex processes like embryonic development and cognition, and how this complex network breaks down in diseases like cancer.
Chandrasekaran did his PhD in biophysics and computational biology at the University of Illinois at Urbana-Champaign. As a graduate student he also worked at the Institute for Systems Biology in Seattle. During his PhD, he developed new systems biology algorithms for modeling regulatory and metabolic networks. Later he moved to Harvard University, where he developed a computational approach to design effective drug combination therapies for countering antibiotic resistance. He is the recipient of the 2011 Howard Hughes Medical Institute (HHMI) International Predoctoral Fellowship and the 2014 William Milton Fund award, and was elected as a junior fellow to the Harvard Society of Fellows in 2013.
At Michigan, Chandrasekaran’s lab will develop multi-scale computational models that span metabolic, transcriptional, and post-translational regulatory networks. These models have several basic biological and medical applications. For example, they will be applied to understand the interplay of metabolic pathways and transcription factors during embryonic stem cell differentiation. On the biomedical front, the models will be used to design effective drug combination therapies for cancer and infectious diseases that have enhanced efficacy, diminished side effects, and reduced potential for developing drug resistance.
Chandrasekaran is looking forward to collaborating with BME faculty, such as Lonnie Shea, Deepak Nagrath and David Sept to tap their expertise in transcriptional regulation, metabolism and modeling. He’s also eager to work with students and scientists from U-M’s top-rated engineering and medical schools to develop computational models for drug discovery and for solving antibiotic resistance.
Neurostimulation for Chronic Pain
Scott Lempka joins BME with the goal of partnering with physicians who both treat and research chronic pain to help elucidate how neurostimulation acts on chronic pain. He does this by combining patient-specific computer models with clinical data, such as quantitative sensory testing and functional neuroimaging, to understand the effects of various therapies – why they work in some patients and not in others.
Lempka completed his PhD at Case Western Reserve University, where he blended computer modeling of deep-brain stimulation for Parkinson’s disease with experimental measurements from animal models. This experience provided him with a skill set for investigating the mechanisms of action of neurostimulation for neurological disorders. This skill let later found a calling when he learned that the technique’s largest application – chronic pain management – was actually poorly understood and had limited clinical success. “Despite being used on tens of thousands of patients a year, and being a multibillion-dollar market, neurostimulation for chronic pain is generally thought to only work in approximately 50 percent of patients,” says Lempka. “Even among patients that are considered ‘responders,’ the pain relief often isn’t enough to dramatically improve their quality of life. Many remain on disability, with great personal and societal costs.”
Lempka realized that to change this, he’d need to learn more about the clinical application of neurostimulation for chronic pain management and about conducting clinical research. So he worked, first as a fellow and then as a staff member, at the Cleveland Clinic’s Center for Neurological Restoration, conducting theoretical and clinical studies of novel forms of neurostimulation for chronic pain management.
In coming to Michigan, Lempka is eager to continue this work, partnering with U-M’s leading clinical pain research groups and pain management specialists, not only to better understand how neurostimulation works on pain, but to innovate more effective therapies going forward.
Metabolic Systems Biology of Cancer
Deepak Nagrath joins BME this winter, bringing expertise in the development of metabolic and nutritional systems biology approaches for cancer and other diseases.
His work combines the experimental technique of metabolic isotope tracing with a computational framework known as 13C-based metabolic flux analysis. Using a systems biology approach, his lab aims to identify the critical metabolic regulators of cancer metastasis and the role the tumor microenvironment plays in modulating cancer cell metabolism. He hopes his studies will provide avenues for targeting cancer cells in a stage-specific manner and for treating tumors’ heterogeneous cell populations with drug cocktails targeting mutually compensatory metabolic pathways.
After completing his PhD from Rensselaer Polytechnic Institute in the area of chromatographic separations, Nagrath joined Harvard Medical School for a postdoc in metabolic and tissue engineering. He then served as an assistant professor at Rice University focused on the systems biology of human disease. Here he mentored students in applying metabolic tracing techniques in cancer metastasis, uncovering metabolic approaches for targeting the tumor microenvironment, and unraveling the metabolic role of exosomes.
Nagrath’s lab has published several recent findings in these areas. In Cell Metabolism, they showed that targeting stromal glutamine synthetase disrupts tumor microenvironment-mediated cancer cell growth and used a synthetic lethal approach to target tumor stroma and cancer cells simultaneously. In eLife, they uncovered the metabolic role of exosomes secreted by tumor microenvironment in cancer metabolism. In Nature Communications, they applied metabolic and bioinformatic tools to analyze genes in the ubiquitin-proteasome proteolytic pathways to determine their molecular interactions with cell metabolism. And in Molecular Systems Biology, they showed that invasive ovarian cancer cells are glutamine-dependent and that glutamine selectively supports high-invasive versus low-invasive ovarian cancer cell growth through glutaminolysis and STAT3 signaling.
In coming to U-M, Nagrath looks forward to strong collaborations with cancer researchers and hopes to support colleagues interested in incorporating metabolic aspects into their research. He is also eager to collaborate with immunologists to decipher metabolic targets for immunotherapy.
James Weiland is establishing his BioElectronic Vision Laboratory in BME, where he will build on more than two decades of work developing technological solutions for visual dysfunction.
Weiland investigates the fundamental mechanisms through which implantable and wearable electronic systems interact with the visual system and other senses, as well as the long-term consequences of such systems on the functional and anatomical organization of the visual system. Based on this understanding, his lab creates and optimizes medical devices designed to improve the quality of life for the visually impaired.
The main projects in his lab include a bioelectronic retinal prosthesis and wearable smart camera. The prosthesis, called the Argus II or bionic eye, provides electrical stimulation to the retina and can offer partial vision restoration to adults with profound blindness. Weiland has been involved in both its preclinical development and clinical testing, and hopes to improve upon the technology, providing greater visual enhancement to users. He also hopes to complement this technology with a wearable smart camera he’s developing. His group has already shown that the camera can guide users around a room and allow them to grasp nearby objects using both auditory and tactile cues; he hopes ultimately it will help them do more complex tasks, from navigating a busy crosswalk to interpreting nonverbal social cues to identifying passersby or a face across a room.
Weiland returns to his alma mater after faculty positions at the Wilmer Ophthalmological Institute of Johns Hopkins University and the University of Southern California. He received all his degrees from U-M, including his BS, MS in electrical engineering, and MS/PhD in BME. He’s eager to make use of campus facilities like Mcity, U-M’s 16-acre simulated pedestrian and roadway environment, to test his technologies. He’s also interested in collaborating with colleagues in engineering and computer science, and at the Kellogg Eye Center, where he has a joint appointment and which is a leading implant center for the Argus II.