Karen K. Hirschi, Ph.D.
Departments of Pediatrics and Molecular & Cellular Biology
Center for Cell and Gene Therapy
Baylor College of Medicine
Department of Bioengineering
B.S., Pennsylvania State University, University Park, 1984
Ph.D., University of Arizona, Tucson, 1990
Postdoc, Harvard Medical School, Boston, MA, 1996
A 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 commitment and differentiation, as well as modulators of vascular cell proliferation and migration during blood vessel assembly. We aim to define mechanisms by which soluble effectors, such as retinoids and TGF-α, and cell-cell junctional components, such as gap junctions, modulate 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). We apply insights gained from the murine embryo model system to modulate the commitment of human embryonic stem cells toward vascular cell fates.
Another focus of our laboratory is investigating the potential of adult and embryonic stem and progenitor 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.
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.
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.
Hirschi, K.K., T.C. Skalak, S.M. Peirce and C.D. Little. (2002) Vascular assembly in natural and engineered tissues. Ann. NY Acad. Science 961:223-242.
Majka, S.M., K.A. Jackson, K. A. Kienstra, M.W. Majesky, M.A. Goodell & K.K. Hirschi. (2003)
Distinct progenitors populations in skeletal muscle are bone marrow-derived and exhibit different cell fates during vascular regeneration. J. Clin. Invest. 111:71-79.
Hirschi, K.K., J.M. Burt, K.D. Hirschi & C. Dai. (2003) Gap junction communication mediates TGF-α activation and endothelial-induced mural cell differentiation. Circ. Res. 93:429-437.
Nadin, B.M., M.A. Goodell & K.K. Hirschi. (2003) Phenotype and hematopoietic potential of side population cells throughout embryonic development. Blood 102:2436-2443.
Lai*, L., B.L. Bohnsack*, K. Niederreither & K.K. Hirschi. (2003) Retinoic acid signaling regulates endothelial cell proliferation during vasculogenesis. Development 130:6465-6474. *Contributed equally
Bohnsack, B.L., L. Lai, P. Dolle & K.K. Hirschi. (2004) Signaling hierarchy downstream of retinoic acid that independently regulates vascular remodeling and endothelial cell proliferation. Genes & Development 18:1345-1358.
Bohnsack, B.L. and K.K. Hirschi. (2004) Red light, green light: signals that coordinately regulate endothelial cell proliferation during vascular development. Cell Cycle 3:1506-1511.
Enciso J.M. and K.K. Hirschi. (2005) Understanding abnormalities in vascular specification and remodeling. Pediatrics 116:228-30.