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. |
