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University of Minnesota Projects

The projects undertaken at our institution will define the key regulatory nodes in the networks that promote stem cells and progenitor cells to adopt a hematopoietic and cardiovascular cell fate – with an aim toward improving clinical options. We will decipher the intracellular, extracellular and paracrine factors that promote stem/progenitor cell specification and differentiation to cardiac, vascular and hematopoietic restricted lineages. In these projects, we will utilize an array of tools and emerging technologies including transgenic mouse models, genetically engineered embryonic and induced pluripotent stem cells, clonal cardiac progenitor cell populations, the decellularized heart, and state-of-the-art high resolution imaging/spectroscopy technologies, which will facilitate our studies and those of our partners at the University of Wisconsin and those associated with the consortium. The overall goal of this proposal is to mechanistically decipher the intracellular and extracellular networks that govern specification and differentiation of stem cells to the cardiovascular and hematopoietic lineages. To address this overall goal, we will pursue the following projects:
Project #1:   To define the transcriptional mechanisms that specify the hematopoietic program in hES- and hiPS-derived mesoderm.
Project #2:   To define the transcriptional and signaling networks that specify the cardiovascular program in mES/EBs, hESC, hiPSC, and cardiac progenitors.
Project #3:   To define the extracellular cues including cell-matrix interactions that direct cardiovascular differentiation and function.
Project #4:   To define the optimal cell populations derived from hESCs and hiPSCs for myocardial regeneration.  
To successfully address these projects and the associated specific aims, we have assembled an outstanding, collaborative research team that has established expertise in stem cell biology and regenerative medicine. The members of the team include:
Daniel J. Garry, M.D., Ph.D., Professor, Medicine and Integrative Biology and Physiology Departments, St. Jude Medical Endowed Chair in Cardiology, Director of the Lillehei Heart Institute and Chief of the Cardiovascular Division will serve as the lead Principle Investigator for the hub and this U01 grant and will direct Project #2.
Doris Taylor, Ph.D., Professor, Integrative Biology and Physiology, Medtronic-Bakken Chair in Cardiac Repair and Director of the Center for Cardiovascular Repair with expertise in stem cell biology, biomedical engineering and extracellular matrix will direct Project #3.
Jianyi Zhang, M.D., Ph.D., Professor, Medicine and Biomedical Engineering Departments, Director of Cellular Therapy for Cardiac Failure who has expertise in myocardial bioenergetics, scaffold design, stem cell biology and High field Magnetic Resonance Imaging/Spectroscopy to assess stem cell function will direct Project #4.  
Michael Kyba, Ph.D., Assistant Professor, Pediatrics Department, Lillehei Endowed Scholar has expertise in hematopoiesis, transcriptional biology and gene targeting in stem cell populations will direct Project #1.
Jonathan Slack, Ph.D., Professor, Tulloch Chair in Stem Cell Biology, Genetics and Genomics, Director of the Stem Cell Institute is a world-renowned expert in developmental biology whose research currently focuses on regenerative medicine and iPSCs, will serve as a Co-Investigator on Project #2 and lead the Skills Development Program for the Research Hub.
Dan Kaufman, M.D., Ph.D., Associate Professor of Medicine and Co-Director of the Stem Cell Institute has expertise in hESCs and hematopoiesis, completed his training in the Thomson laboratory at UW and will serve as a Co-Investigator on Projects #1, #2 and #4.

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