Regulation of blood vessel development
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-β, and cell-cell junctional components, such as gap junctions,
modulate vascular cell phenotype and cell cycle progression. We utilize in vitro coculture systems to study interactions
between vascular cells and their precursors. In vivo regulation of blood vessel assembly is studied in transgenic mouse
models.
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 adult stem 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.
Selected Publications
Hirschi KK, Rohovsky SA, D'Amore PA (1998) PDGF, TGF-β and heterotypic cell-cell
interactions mediate the recruitment and differentiation of 10T1/2 cells to a smooth muscle fate.
Journal of Cell Biology 141:805-814.
Niklason L, Gao C, Abbott P, Hirschi KK, Houser M, Marini D, Langer R (1999) Functional arterial
grafts grown in vitro. Science 284:422-425.
Jackson KA, Majka SM, Wang H, Pocius J, Hartley C, Majesky MW, Michael L, Entman M, Hirschi KK,
Goodell MA. (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells.
Journal of Clinical Investigation 107:1395-1402.
Hirschi KK, Goodell MA (2001) Common origins of blood and blood vessels in adults?
Differentiation 68:186-192.
Hirschi KK, Skalak TC, Peirce S, Little CD (2002) Vascular assembly in natural and engineered
tissues. Annals of the New York Academy of Sciences 961:223-242.
Majka SM, Jackson KA, Kienstra KA, Majesky MW, Goodell MA, Hirschi KK (2003) Distinct
populations of vascular progenitors in skeletal muscle are derived from bone marrow and exhibit different
cell fates during vascular regeneration. Journal of Clinical Investigation 111:71-79.
Nadin BM, Goodell MA, Hirschi KK (2003) Phenotype and hematopoietic potential of side population
cells throughout embryonic development. Blood 102:2436-2443.
Lai L, Bohnsack BL, Niederreither K, Hirschi KK (2003) Retinoic acid regulates endothelial cell
proliferation during vasculogenesis. Development 130:6465-6474.
Contact Information
- Karen K. Hirschi, Ph.D.
- Department of Pediatrics
- Baylor College of Medicine
- One Baylor Plaza N1030
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-7771
- Fax: (713) 798-1230
- E-mail: khirschi@bcm.tmc.edu
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