Contact Information:
khirschi@bcm.edu
713-798-7771

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Education:
PhD - University of Arizona
Postdoc - Harvard Medical School

Research Interests: 
Regulation of Vascular Development
Vascular Regeneration
Vascular Potential of Stem & Progenitor Cells

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-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 (co-culture systems to study interactions between vascular cells and their precursors).

We use information derived from the murine embryo model system to modulate the commitment of pluripotent human stem cells (human embryonic stem [hES] and induced pluripotent stem [iPS] cells) toward vascular cell fates, and to understand the distinct molecular mechanisms that govern the differentiation of human endothelial cells.

Insights gained from our cell and developmental studies are applied to the genesis and optimization of clinically relevant strategies including autologous vascular cell and gene therapy, creation of blood vessels grafts, and vascularization of engineered tissues.  These efforts are largely part of multi-disciplinary, inter-institutional projects that we have designed to translate mechanisms of tissue morphogenesis into strategies to repair damaged and diseased tissues.

 

Selected Publications:

Niklason, L., C. Gao, P. Abbott, K.K. Hirschi, M. Houser, D. Marini and R. Langer. (1999) Functional arterial grafts grown in vitro. Science 284:422-425.

Hirschi, K.K., L. Lai, N.S. Belaguli, D. Dean, R.J. Schwartz & W.E. Zimmer. (2001) TGF-b         induction of a smooth muscle cell phenotype requires transcriptional and post-     transcriptional control of serum response factor. J. Biological Chemistry 277:6287-95.

Majka, S.M., K.A. Jackson, K.A. Kienstra, M.W. Majesky, M.A. Goodell & K.K. Hirschi. (2003) Distinct populations of vascular progenitors in skeletal muscle are bone marrow-derived and exhibit different cell fates during vascular regeneration. J. Clinical Investigation 111:71-79.

Hirschi, K.K., J.M. Burt, K.D. Hirschi &. C. Dai. (2003) Gap junction communication mediates TGF-b 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.

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.

Enciso, J.M. and K.K. Hirschi (2005) Understanding abnormalities in vascular specification and remodeling.  Pediatrics 116:228-30.

Bohnsack, B.L., L. Lai, J. Northrop, M.J. Justice & K.K. Hirschi. (2006) Visceral endoderm function is regulated by quaking and required for vascular development. Genesis 44:93-104.

Kienstra, K.A., K.A. Jackson & K.K. Hirschi. (2008) Mechanism and degree of injury dictate contribution of bone marrow-derived cells to neovascularization. J. Pediatric Research 63:131-136.

Hirschi, K.K. D.A. Ingram & M.C. Yoder. (2008) Assessing identity, phenotype, and fate of endothelial progenitor cells. Arteriosclerosis, Thrombosis and Vascular Biology 28:1584-1595.

Goldie, L.C., J. Lucitti, M.E. Dickinson & K.K. Hirschi. (2008) Cell signaling directing the formation and function of hemogenic endothelium during murine embryogenesis. Blood 112:3194-3204.

Kelly, M.A. and K.K. Hirschi. (2009) Signaling hierarchy regulating human endothelial cell           development. Arteriosclerosis, Thrombosis and Vascular Biology (in press).