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Professor and Head, Department of Biomedical Engineering
Director, Stem Cell Institute
Preceptor, Medical Scientist Training Program (Combined MD/PhD Training Program)
Faculty, Masters Program in Stem Cell Biology
Postdoctoral Fellow, Mayo Clinic College of Medicine
PhD, University of Minnesota (Biomedical Engineering), 2000
MS, University of Minnesota (Biomedical Engineering), 1998
BS, College of St. Benedict/St. John's University (Mathematics and Natural Science), 1994
System Regeneration Lab
The mission of our research program is to investigate the mechanisms of stem cell differentiation, especially in the context of the cardiovascular system. Driven by this mission, we also seek to generate new technologies that advance stem cell biology and promote translation of stem cell research into clinical practice. A primary strength of our program is the ability to span multiple subdisciplines within both basic science (i.e., stem cell biology, cell-cell fusion and extracellular matrices) and engineering (cytometry instrumentation and microfabrication) fields. Equally important is the high caliber of our team and the wonderful momentum they have built with hard work, strong intellect and scientific curiosity. Below is a description of the primary research projects within our research program.
I. Stem Cell Differentiation via Cell Fusion
Stem cell or progenitor cell transplantation has been proposed as a means to recover heart muscle function with damage or disease. However recent experience has taught that most transplanted cells do not successfully engraft and do not become integral components of the myocardium. Our group was among the first to discover that fusion between donor stem cells and recipient cardiomyocytes promotes stem cell engraftment, survival and differentiation. Thus, we hypothesize that cardiac differentiation of stem cells and ultimately myocardial repair after infarction might be stimulated by the transplantation of stem cells poised to fuse with cardiomyocytes of the damaged ventricle.
II. Stem Cell Differentiation via Extracellular Matrix Interactions
Extracellular matrix (ECM)-based scaffolds have been proposed as a "bio-inspired" means to deliver stem cells to damaged myocardial tissue. However, our knowledge of the impact of cell-ECM interactions on cell fate processes of stem cells is limited. Particularly lacking is a clear understanding of the impact of 3D stem cell-ECM interactions on induction or repression of differentiation. We hypothesize that ECM interactions alone are capable of driving lineage-specific differentiation of stem cells and our group is particularly interested in differentiation of cardiac cell types in this context.
III. Multiphoton Flow Cytometry to Guide Stem Cell Transplantation
The future of stem cell transplantation depends on the identification of noninvasive biomarkers to characterize cells and cell aggregates prior to transplantation. Characterization is needed minimally to define cell state and ideally to predict those cells best poised to contribute to a specific tissue type. We hypothesize that intrinsic metabolic signatures detected with multiphoton microscopy provide noninvasive biomarkers indicative of stem cell state. We have recently coupled multiphoton optics to a flow cytometry system (MPFC) that can analyze such intrinsic signatures of single cell and multicell aggregates in a high-throughput manner. This system is also the first of its kind to detect extrinsic fluorescent labels and dyes of cells within multicell aggregates or microtissues in a high-throughput manner.