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Faculty Guo-Hua Fong
Assistant Professor of Cell Biology
fong@nso2.uchc.edu
Areas of Interest:
We are trying to understand how blood vessel growth is controlled, an
important topic that relates to several life-threatening diseases such
as tumor metastasis and cardiac ischemia. As tissue masses grow,
metabolic activities increase, resulting in faster oxygen consumption
and reduced oxygen tension (hypoxia) inside the tissue. Hypoxia triggers
the accumulation of hypoxia inducible factors (HIFs) (bHLH-PAS domain
containing transcription factors), which in turn activate the expression
of vascular endothelial growth factor-A (VEGF-A). VEGF-A is required for
blood vessel growth under essentially all circumstances (embryonic
development, tumor angiogenesis, wound healing, etc.). Thus, hypoxia
induction of VEGF-A expression and subsequent signaling processes
initiated by VEGF-A and its cell surface receptors appear to be a
central pathway governing the growth of blood vessels.
Research projects in our laboratory are aimed at understanding the
mechanisms of VEGF-A signaling and HIF function in animal models. By
genetic manipulation of the mouse genome, we modify the properties of
VEGF-A receptors and HIF-2 and analyze the consequences of such
modifications on blood vessel growth in animal model (knockout and
transgenic mice). To complement these in vivo studies, in vitro
approaches are also being taken to investigate mechanisms of
hypoxia-induced stabilities of HIF-2 and cross-talks between VEGF-A
receptors.
Selected Publications:
Duan L-J, Venturelli, C., Zhang. Y., Drysdale, L., Nagy A. and Fong,
GH. (2004) Flt-1 functions as a decoy receptor in gastrulation but a
signaling molecule in vasculogenesis Blood (Submitted).
Lelievre, E and Fong, G-H., RNA Interference in ES cell-derived
Embryoid Bodies as a Tool to Study Gene Functions during Early Vascular
Development. (2004) Genesis (Submitted).
Duan, L-J., Imamoto, A. and Fong, G-H. (2004) Dual roles of the
C-terminal Src kinase (Csk) duing developmental vascularization Blood
103(4), 1370-2.
Duan, L-J., Nagy A. and Fong, G-H. (2003) Gastrulation and
Angiogenesis, not Endothelial Specification and Vasculogenesis, Is
Sensitive to Partial Deficiency in Vascular Endothelial Growth Factor-A
in Mice. Biol Reprod 69(6), 1852-8.
Peng, J., Zhang, L. Drysdale, L. and Fong, G-H. (2000) The
Transcription Factor EPAS-1/HIF-2 Plays an Important Role in Vascular
Remodeling. Proc. Natl. Acad. Sci. USA 97 (15): 8386-8391. |
