BME Project #2: Quantification of immunofluorescence staining images of the stomach

Faculty Mentor: Zhongming Liu, zmliu@umich.edu

Prerequisites: Familiarity with MATLAB and Python programming, basic understanding of signal processing. Knowledge of deep learning or machine learning is a plus.

Project Description: This project is part of the research examining the relationship between gastric dysfunctions and the underlying cellular-level pathophysiological mechanism in Type-I diabetes-induced gastroparesis in rats. Gastroparesis is clinically diagnosed by delayed gastric emptying without mechanical obstruction and has diverse etiologies. Its treatment remains challenging, potentially due to its heterogeneous origins. In this research, we focus on the Type-I diabetes-induced gastroparesis rat model and aim to characterize the gastric dysfunctions and associate the changes in gastric functions with the cellular changes in the peripheral nervous system and the interstitial cells of Cajal. 

This project aims to develop image analysis approaches to quantify the distribution of inhibitory and excitatory motor neurons within the enteric nervous system and the interstitial cells of Cajal on the immunofluorescence staining images of the stomach. The student will be involved in the development and refinement of algorithms and process the data with the developed algorithm. 

Research Mode: In-Person

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BME Project #3: Differentiating neuronal control of the gastric motor functions in rats

Faculty Mentor: Zhongming Liu, zmliu@umich.edu

Prerequisites: Basic understanding of magnetic resonance imaging technique and experience in handling rats.

Project Description: The stomach works as a food reservoir and a pump to store food, mix, grind, and finally empty it out at an effective rate for nutrient absorption in the intestines. Its functions are under the fine control of both parasympathetic and sympathetic nerves. In this project, we aim to differentiate the functional roles of the parasympathetic and sympathetic nerves on various aspects of gastric motor functions at an organ level using MRI in rats. We will sever the parasympathetic or sympathetic branches innervating the stomach using surgical or chemical approaches and observe the changes in gastric motor functions. The student will participate in and assist in the MRI image acquisition and help monitor the depth of anesthesia throughout the imaging experiments.  

Research Mode: In-Person (lab)

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BME Project #4: Modulating myeloid cell phenotypes with immunomodulatory nanoparticles

Faculty Mentor: Lonnie Shea, Ph.D., ldshea@umich.edu

Prerequisites: Willingness to assist with surgery, extensively handle mice, use needles, and perform dissection and necropsy procedures.

Project Description: Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with a <50% 5-year survival rate. It is characterized by progressive deposition of excessive extracellular matrix proteins in the lungs (i.e., scarring) due to a dysfunctional wound healing response. The cause of IPF remains unknown and there is no cure and few treatments that slow progression. A key mechanism of IPF disease is the accumulation of dysregulated lung macrophages that promote fibrosis. While healthy lung macrophages are seeded in the lung during embryonic development, IPF macrophages are largely derived from circulating monocytes. We know that depleting these disease-causing macrophages from the lung can treat IPF in mice. However, macrophage depletion is not a viable strategy in the clinic because it causes significant side effects, especially dangerous immunosuppression. Previously, we developed immunomodulatory nanoparticles that are preferentially phagocytosed (internalized) by circulating monocytes and macrophages in the bloodstream. The particles cause immune cells to reduce inflammatory behaviors and acquire a pro-regenerative function instead. We have previously demonstrated that in cancer, these particles can reduce tumor size and prevent metastasis in mice. In spinal cord injury, the particles can improve mobility of injured mice by reducing inflammation. In IPF mouse models, we hypothesize that the particles will be phanocytosed by circulating IPF monocytes and prevent them from turning into fibrosis-causing macrophages in the lungs. Preliminary data suggests the particles reduce lung fibrosis in mice, supporting our hypothesis. This project is the first application of our nanoparticles in lung injury and addresses an urgent clinical need for improved IPF therapies.

Research Mode: In person (in the lab)

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BME Project #5: Biological Melanoma Tissue Phantom Characterization

Faculty Mentor: Mary-Ann Mycek, mycek@umich.edu

Prerequisites: Some experience or familiarity with cell culture, microscopy, and quantitative image analysis would be helpful, but not required. Willingness to learn and safely execute BSL2 level (human) cell culture, sample handling, and analysis.

Project Description: There is a significant unmet need for accurate early-stage skin cancer screening, with a particular need for technology that can detect early or pre-cancer tissue stages of melanoma in patients with widely varying skin tones. One particularly promising imaging strategy for early cancer detection focuses on using the light scattering properties of tissue to be able to identify suspicious lesions. While new technologies are being developed to support this endeavor, there is a concurrent need to develop and characterize biologically inspired melanoma tissue phantoms, in order to verify and validate new imaging technologies. 3D tissue culture based models of normal full thickness skin (epidermis/dermis) and melanoma exist and have been well characterized in terms of their ability to recapitulate tissue morphology and physiology for normal human skin and melanoma lesions as they mature and develop. However, these 3D tissue engineering models have not been well characterized in terms of features such as cellular, intracellular, and extracellular matrix composition and organization, which may affect the tissue light scattering signatures of the constructs.This project would focus on culturing these 3D tissue-engineered skin models while characterizing and quantifying these features using histology, light microscopy, and confocal or lightsheet microscopy with targeted fluorophore staining for cells and organelles. Second Harmonic Generation imaging would also be used to characterize collagen composition and orientation. The student researcher working on this project would be involved with optimizing culture conditions, imaging and staining protocols, and developing and optimizing quantitative image analysis workflows that will allow us to correlate light scattering properties of normal and pathologic tissues to meaningful biological parameters of the tissue.

Research Mode: In Person

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BME Project #6: Understanding How Type-2 Diabetes Affects Female Bone Quality

Faculty Mentor: David Kohn, dhkohn@umich.edu

Prerequisites: Diligence and commitment 

Project Description: This project consists in evaluating changes in bone quality with Type-2 Diabetes and obesity. The characterization process involves several techniques ranging from, Nanointentation, histology to micro-computed tomography (micro-CT). The participation in this project may involve animal handling and monitoring and specimens dissection for sample preparation and storage.  

Research Mode: In Person. All work will be conducted in person at the School of Dentistry.

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BME Project #7: Advances in Drug Delivery: Overcoming Phagocytic Clearance of Therapeutic Nanoparticles

Faculty Mentor: Alexandra Piotrowski-Daspit, Ph.D., asapd@umich.edu

Prerequisites: general lab experience, maintaining a lab notebook, cell culture

Project Description: A major barrier to intravenous (IV) nanoparticle (NP) delivery of therapeutic agents in the body is the rapid clearance of these vehicles by the mononuclear phagocyte system (MPS), primarily through intravascular phagocytic cells in the liver and spleen. This clearance reduces the dose of NPs available in circulation, thereby limiting the amount of NPs that are able to reach intended tissues to treat disease. Our laboratory’s strategy to overcome this barrier is to preoccupy phagocytic cells with benign cargo-free “decoys” before administering a therapeutic NP formulation, allowing the therapeutic NPs to avoid this filtration process and accumulate in target tissues and cell types. The student participating in this project will contribute to research focusing on bypassing MPS clearance and enhancing NP delivery efficiency. The project will leverage our previously developed polymeric NP platforms and include biological assessments both pre- and post- decoy occupation. Additionally, the project will study the effects of decoy pre-administration timing, dose, and the potential consequences of repeat dosing on long-term toxicity and immunogenicity.

Research Mode: In-Person (in the lab)

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