The role of tumor microenvironment in tumor progression and therapeutic resistance with a focus on vascular niche.
Endothelial cells, cancer stem cells, angiogenesis, endothelial-mesenchymal transition, macrophage transition, metabolic dysfunction, translational control, brain tumor, and lung cancer.
Description of Research
Tumors have been recognized as organ-like tissues of extreme complexity. Stromal cells, extracellular matrix, and soluble factors constitute the microenvironment that fuels tumor progression and fosters therapeutic resistance. Overgrown, topologically and structurally abnormal blood vessels characterize the microenvironment of most highly malignant solid tumors including brain tumor and lung cancer. The newly formed vasculature creates an aberrant “vascular niche” that regulates the proliferation, apoptosis, differentiation, and migration of tumor cells, cancer stem cells, and immune cells. Our studies focus on the interaction of vascular endothelial cells with cancer stem cells and immune cells, which promotes tumor progression, induces therapeutic resistance, and protects tumor from host immunity. We employ various approaches and methods of biochemistry and biophysics, molecular and cellular biology, and genetics of vertebrate models including zebrafish and mouse, to dissect the convergent and divergent regulatory pathways. The long-term objective of our laboratory is to identify the key mechanisms that control vascular niche-mediated cancer development, as well as to develop new vasculotherapies for the treatment of brain tumor and lung cancer.
Main research area includes (1) Vascular abnormity mediated by endothelial-mesenchymal transition, (2) Vascular niche for the maintenance of stemness in cancer stem cells, (3) Translational control in cancer stem cells, and (4) Metabolic dysfunction in tumor-associated endothelial cells.
Eswarappa SM, Potdar AA, Koch WJ, Fan Y, Vasu K, Lindner D, Willard B, Graham LM, DiCorleto PE, Fox PL.: Programmed Translational Readthrough Generates Antiangiogenic VEGF-Ax. Cell. 157(7): 1605-18, June 2014.
Fan Y, Potdar AA, Gong Y, Eswarappa SM, Donnola S, Lathia JD, Hambardzumyan D, Rich JN, Fox PL.: Profilin-1 phosphorylation directs angiocrine expression and glioblastoma progression through HIF-1α accumulation. Nat Cell Biol. 16(5): 445-456, May 2014.
Gong Y, Zhao Y, Li Y, Fan Y, Hoover-Plow J: Plasminogen regulates cardiac repair after myocardial infarction through its non-canonical function in stem cell homing to the infarcted heart. J Am Coll Cardiol. 63(25): 2862-2872, July 2014.
Fan Y., Arif A., Gong Y., Jia J., Eswarappa S.M., Willard B., Horowitz A., Graham L.M., Penn M.S., Fox P.L.: Stimulus-dependent phosphorylation of profilin-1 in angiogenesis. Nat. Cell Biol. 14(10): 1046-56, Oct 2012.
Fan Y., Eswarappa S.M., Hitomi M., Fox P.L.: Myo1c facilitates G-actin transport to the leading edge of migrating endothelial cells. J. Cell. Biol. 198(1): 47-55, Jul 2012.
Gong Y., Fan Y., Hoover-Plow J.: Plasminogen regulates stromal cell-derived factor-1/CXCR4-mediated hematopoietic stem cell mobilization by activation of matrix metalloproteinase-9. Arterioscler. Thromb. Vasc. Biol. 31(9): 2035-43, Sep 2011.
Fan Y., Gong Y., Ghosh P.K., Graham L.M., Fox P.L.: Spatial coordination of actin polymerization and ILK-Akt2 activity during endothelial cell migration. Dev. Cell 16(5): 661-74, May 2009.
Gong Y-Q., Fan Y., Wu D-Z., Yang H., Hu Z-B., Wang Z-T.: In vivo and in vitro evaluation of erianin, a novel anti-angiogenic agent. Eur. J. Cancer Oxford, England: 1990) 40(10): 1554-65, Jul 2004.
Fan Y., Wu D-Z., Gong Y-Q., Zhou J-Y., Hu Z-B.: Effects of calycosin on the impairment of barrier function induced by hypoxia in human umbilical vein endothelial cells. Eur. J. Pharmacol. 481(1): 33-40, Nov 2003.
Fan Y., Wu D-Z., Gong Y-Q., Xu R., Hu Z-B.: Metabolic responses induced by thrombin in human umbilical vein endothelial cells. Biochem. Biophys. Res. Commun. 293(3): 979-85, May 2002.
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Last updated: 11/24/2014
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