Karen K. Hirschi, Ph.D.
Departments of Pediatrics and Molecular and Cellular Biology, Baylor College of Medicine
Department of Bioengineering, Rice University
Ph.D., University of Arizona, Tucson, AZ
Postdoctoral, Harvard Medical School, Boston, MA
Regulation of Vascular Development Vascular Potential of Adult Stem Cells
The primary interest of our laboratory is to understand, at the cellular and molecular level, the events leading to blood vessel formation. We are interested in elucidating regulators of vascular cell (endothelial and smooth muscle) recruitment, proliferation and differentiation needed for blood vessel assembly and maintenance. We aim to define mechanisms by which soluble effectors, such as retinoids and TGF- b , and cell-cell junctional components, such as gap junctions, modulate vascular cell phenotype and cell cycle progression. We use the mouse model system to study the regulation of blood vessel assembly in vivo (transgenesis), in situ (embryo culture) and in vitro (coculture systems to study interactions between vascular cells and their precursors).
Another focus of our laboratory is investigating the potential of adult stem cells to contribute to neovascularization in response to tissue injury and growth. Utilizing bone marrow transplantation and localized delivery techniques, we study mechanisms by which stem and progenitor cells are recruited, induced to differentiate into vascular cells, and functionally integrated into existing vascular networks.
Insights gained from our cell and developmental studies are applied to the optimization of clinically relevant treatments including autologous vascular cell and gene therapy, creation of blood vessels grafts, and vascularization of engineered tissues.
Bohnsack BL, Lai L, Northrop J, Justice MJ & Hirschi KK. (2006) Visceral endoderm function is regulated by quaking and required for vascular development. Genesis 44:93-104.
Enciso JM, Hirschi KK. Understanding abnormalities in vascular specification and remodeling. Pediatrics. 116(1):228-230, 2005.
Bohnsack BL, Hirschi KK. Red light, green light: signals that control endothelial cell proliferation during embryonic vascular development. Cell Cycle. 3(12):1506-1511, 2004.
Huss WJ, Lai L, Barrios RJ, Hirschi KK, Greenberg NM. Retinoic acid slows progression and promotes apoptosis of spontaneous prostate cancer. Prostate. 61(2):142-152, 2004.
Bohnsack BL, Lai L, Dolle P, Hirschi KK. Signaling hierarchy downstream of retinoic acid that independently regulates vascular remodeling and endothelial cell proliferation. Genes Dev. 18(11):1345-1358, 2004. Hirschi KK, Majesky MW. Smooth muscle stem cells. Anat Rec A Discov Mol Cell Evol Biol. 276(1):22-33, 2004.
Bohnsack BL, Hirschi KK. Nutrient regulation of cell cycle progression. Annu Rev Nutr. 24:433-453, 2004.
Olmsted-Davis EA, Gugala Z, Camargo F, Gannon FH, Jackson K, Kienstra KA, Shine HD, Lindsey RW, Hirschi KK, Goodell MA, Brenner MK, Davis AR. Primitive adult hematopoietic stem cells can function as osteoblast precursors. Proc Natl Acad Sci U S A. 100(26):15877-15882, 2003.
Abramowitz J, Dai C, Hirschi KK, Dmitrieva RI, Doris PA, Liu L, Allen JC. Ouabain- and marinobufagenin-induced proliferation of human umbilical vein smooth muscle cells and a rat vascular smooth muscle cell line, A7r5. Circulation. 108(24):3048-3053, 2003.
Lai L, Bohnsack BL, Niederreither K, Hirschi KK. Retinoic acid regulates endothelial cell proliferation during vasculogenesis. Development. 130(26):6465-6474, 2003.
Nadin BM, Goodell MA, Hirschi KK. Phenotype and hematopoietic potential of side population cells throughout embryonic development. Blood. 102(7):2436-2443, 2003.
Hirschi KK, Burt JM, Hirschi KD, Dai C. Gap junction communication mediates transforming growth factor-beta activation and endothelial-induced mural cell differentiation. Circ Res. 93(5):429-437, 2003.
McKinney-Freeman SL, Majka SM, Jackson KA, Norwood K, Hirschi KK, Goodell MA. Altered phenotype and reduced function of muscle-derived hematopoietic stem cells. Exp Hematol. 31(9):806-814, 2003.
Bohnsack BL, Hirschi KK. The FAKs about blood vessel assembly. Circ Res. 92(3):255-257, 2003.
Majka SM, Jackson KA, Kienstra KA, Majesky MW, Goodell MA, Hirschi KK. Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. J Clin Invest. 111(1):71-79, 2003.
Hirschi, K.K. & M.A. Goodell (2001) Common origins of blood and blood vessels in adults? Differentiation 68:186-192.
Jackson*, K.A., S.M. Majka*, H. Wang, J. Pocius, C. Hartley, M.W. Majesky, L. Michael, M. Entman, K.K. Hirschi & M.A. Goodell. (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clin. Invest. 107: 1395-1402 *Contributed equally.
Niklason L., C. Gao, P. Abbott, K.K. Hirschi, M. Houser, D. Marini & R. Langer. (1999) Functional arterial grafts grown in vitro. Science 284:422-425.
Hirschi K.K., S.A. Rohovsky & P.A. D'Amore. (1998) PDGF, TGF- b and heterotypic cell-cell interactions mediate the recruitment and differentiation of 10T1/2 cells to a smooth muscle fate. J. Cell Biol. 141:805-814.