Research Scientist, Miami VAHCS Associate Professor, University of Miami Miller School of Medicine Contact Information Location: Research Service VAM(151), Room211, 1201 NW 16th street, Miami FL 33125 Office Phone: 305-575-7000, ext 3998 Lab Phone: 305-575-7000, ext 6593, 4485 Fax: 305-575-3126 Email: hyu@med.miami.edu Affiliations Research Service, Miami VAHCS Vascular Biology Institute, Department of cellular and Molecular Pharmacology, University of Miami School of Medicine Education Undergraduate and Graduate B.S.
Fudan University, Shanghai, China, 1982.
Ph.D.
University of Southern California, 1993. Post-Graduate Training
Post-doctoral Fellow – Gene Therapy Laboratory, University of Southern California School of Medicine with Dr. W. French Anderson, 1993-1996.
Description of Research Expertise Research Interests -Impact of aging on CXCR4 surface expression on bone marrow-derived cells -CXCR4/SDF-1 interaction and signaling pathway
-Mobilization and homing of Progenitor cells
-Roles of progenitor cells in angiogenesis and atherosclerosis. Key Words CXCR4, SDF-1, bone marrow cells, endothelial progenitor cells, angiogenesis, atherosclerosis, cardiovascular diseases, mobilization, migration, engraftment. Research description Vascular occlusion resulting in ischemia is a major cause of heart attack, stroke and peripheral arterial disease. Angiogenesis (natural revascularization) is stimulated by the signaling factors released from the ischemia tissue. Bone marrow-derived cells (BMC) are mobilized into circulation in response to signaling proteins. Among these proteins, the chemotactic cytokine Stromal Cell Derived Factor-1 (SDF-1) is particularly important as an initiator of angiogenesis and vascular repair. SDF-1 acts through binding with the cell surface receptor known as CXCR4. As a result of SDF-1/CXCR4 axis signaling, the BMCs home to the ischemic tissue where they participate in new vessel growth. The amount of surface CXCR4 expression on progenitor cells is critical for the ability of cells being mobilized and engrafted. The focus of our laboratory is to identify the specific changes in CXCR4 surface expression and SDF-1/CXCR4 signaling pathway which is responsible for the impaired revascularization ability of aged BMCs. We have found that aging adversely impacts angiogenesis. SDF-1 is inefficient to promote angiogenesis in aged mice. CXCR4 surface expression on BMC from old mice is significantly lower than that of young mice. We are studying the impact of aging on CXCR4 expression in the subpopulations of BMC, and the causes for the reduced CXCR4 surface expression on BMC from old mice. We try to determine the aging effect on SDF-1/CXCR4 signaling, including Akt phosphorylation, eNOS activation and ROS production. We are illustrating in vitro the effect of differential surface CXCR4 expression on progenitor cell migration, tube formation, and its interaction with mature endothelial cells. We are studying how precursor cells homing to ischemic tissues and what functions they provide during neovascularization using a hindlimb ischemia mouse model. Another project is to study the role of Bone marrow-derived cells, particularly neutrophil granulocytes, in atherosclerosis. We are studying the role of CXCR4 expression on the homing of neutrophil onto plaques, and will determine the contribution of neutrophils to plaque formation in an atherosclerotic prone ApoE knockout mouse model. These fundamental mechanistic studies will enhance our understanding of stem cell biology, and will enable us to refine cell-based therapeutic strategies for vascular diseases. Representative Publication 1. Tan, Y, Shao H, Eton D, et al, Yu H. Stromal Cell-Derived Factor-1 Enhances Pro-Angiogenic Effect of Granulocyte Colony Stimulating Factor. Cardiovasc Res. 73: 823-832, 2007. http://www.ncbi.nlm.nih.gov/pubmed/17258698 2. Shao H, Tan Y, et al., Yu H. Statin and Stromal Cell Derived Factor-1 Additively Promote Angiogenesis by Enhancement of Progenitor Cells Incorporation into New Vessels. Stem Cells. 26:1376-1384, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18308946 3. Yu H, Feng Y. The Potential of Statin and Stromal Cell-derived Factor-1 to Promote Angiogenesis. Cell Adhesion and Migration. 2 (4):254-257, 2008. http://www.landesbioscience.com/journals/celladhesion/article/6818 4. Wu Q, Shao H, Eton D, et al., Webster KA, Yu H Extracellular calcium increases CXCR4 Expression on Bone Marrow-derived Cells and Enhances Pro-Angiogenesis Therapy. J Cell Mol Med. 2009 In press. DOI 10.1111/j.1582-4934.2009.00691.x http://www.ncbi.nlm.nih.gov/pubmed/19220581 5. Tan Y, Li Y, et al., Webster KA, Yan J, Yu H, Cai L and Li X. A novel CXCR4 antagonist derived from human SDF-1b enhances angiogenesis in ischemic mice. Cardiovascular Res. 82:513-521, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19196827 |
