PhD University of Pennsylvania, USA
Tumor angiogenesis, anti-angiogenic proteins and cancer therapeutics:
Angiogenesis (new blood vessel formation) is essential for tumor growth and metastasis. Anti-angiogenesis is a promising anticancer therapeutic approach. We focus on investigating novel endogenous angiogenesis inhibitor proteins that contain the thrombospondin type 1 repeat domain (TSR) and their function and development into anti-angiogenic cancer drugs. These proteins are not only valuable for anticancer drug development, but also important for maintaining angiogenesis homeostasis in normal tissues. We have identified 3 novel endogenous anti-angiogenic proteins: Isthmin, ADAMTS5 and ADAMTS4. We are currently investigating their pathophysiological function and therapeutic applications. In addition, we are studying tumor endothelial cell biology and developing targeted drug delivery for liver cancer using tumor endothelial cell surface markers.
Angiogenesis and liver organogenesis in zebrafish model:
Angiogenesis is very important for cardiovascular biology and medicine. It is essential for all tissue formation and growth. We use zebrafish as a model organism to study angiogenesis and liver development. Genes of interest include Augmenter of Liver Regeneration (ALR), Hepatocyte Growth Factor (HGF) and histone deacetylases (HDACs).
Venugopal S, Chen M, Liao W, Er SY, Wong WS, R. Ge*. Isthmin is a novel vascular permeability inducer that functions through cell-surface GRP78-mediated Src activation. Cardiovasc Res. 107:131-42, 2015. PubMed link
Chen, M., Y. Zhang, V. C. Yu, Y-S Chong, T. Yoshioka and R. Ge*. Isthmin targets cell-surface GRP78 and triggers apoptosis via induction of mitochondrial dysfunction. Cell Death Differ. 21:797-810, 2014. PubMed link
Sharghi-Namini S, Tan E, Ong LL, Ge R*, Asada* HH. Dll4-containing exosomes induce capillary sprout retraction in a 3D microenvironment. Sci Rep. 4:4031, 2014. PubMed link
B. E. Attia, C. Yang, J. Hedrick, J. P. K. Tan, N. Rao, Y.Y. Yang* and R. Ge*. Insights into EPR Effect versus lectin-mediated targeted delivery: biodegradable polycarbonate micellar nanoparticles with and without galactose surface decoration. Small 10:4281-6, 2014. PubMed link
Rao N, Ke Z, Liu H, Ho CJ, Kumar S, Xiang W, Zhu Y, R. Ge*. ADAMTS4 and its proteolytic fragments differentially affect melanoma growth and angiogenesis in mice. Int. J. Cancer 133:294-306, 2013. PubMed link
Kumar, S., S. Sharghi-Namini, N. Rao and R. Ge*. ADAMTS5 functions as an anti-angiogenic and anti-tumorigenic protein independent of its proteoglycanase activity. Am. J. Pathol. 181:1056-68, 2012. PubMed link
Ge R*, Tan E, Sharghi-Namini S, Asada HH. Exosomes in cancer microenvironment and beyond: have we overlooked these extracellular messengers? Cancer Microenviron. 5:323-32, 2012. PubMed link
Li Y, Farooq M, Sheng D, Chandramouli C, Lan T, Mahajan NK, Kini RM, Hong Y, Lisowsky T, R. Ge*. Augmenter of liver regeneration (alr) promotes liver outgrowth during zebrafish hepatogenesis. PLoS One 7:e30835, 2012. PubMed link
Zhang Y, Chen M, Venugopal S, Zhou Y, Xiang W, Li YH, Lin Q, Kini RM, Chong YS, R. Ge*. Isthmin exerts pro-survival and death-promoting effect on endothelial cells through alphavbeta5 integrin depending on its physical state. Cell Death Dis. 2:e153, 2011. PubMed link
Xiang W, Ke Z, Zhang Y, Cheng GH, Irwan ID, Sulochana KN, Potturi P, Wang Z, Yang H, Wang J, Zhuo L, Kini RM, R. Ge*. Isthmin is a novel secreted angiogenesis inhibitor that inhibits tumor growth in mice. J. Cell. Mol. Med. 15:359-74., 2011. PubMed link
Jia, J., J. Wang, M. Teh, W. Sun, J. Zhang, I. Kee, P. K-H Chow, R. C. M-Y. Liang, M. C.M. Chung, R. Ge*. Identification Of Proteins Differentially Expressed Between Capillary Endothelial Cells Of Hepatocellular Carcinoma And Normal Liver In An Orthotopic Rat Tumor Model Using 2D-DIGE. Proteomics 10:224-34, 2010. PubMed link
Farooq, M., K.N. Sulochana, X. Pan, J. To, D. Sheng, Z. Gong, R. Ge*. Histone deacetylase 3 (hdac3) is specifically required for liver development in zebrafish. Dev. Biol., 317:336-53, 2008. PubMed link
Sulochana, KN, H. Fan, S. Jois, S. Vivekanandan, F. Sun, R. M. Kini, and R. Ge*. Peptides Derived From Human Decorin Leucine Rich Repeat 5 Inhibit Angiogenesis. J. Biol. Chem. 280:27935-27948, 2005. PubMed link
Ge, R and R. M. Kini, Small Peptides With Potent Anti-Angiogenic Activities. US patent No. 7,317,003, 2008.
Ge, R and R. M. Kini, Small Peptides with Potent Anti-Angiogenic Activities. US patent No. 6,200,954, 2001.