PhD University of Pennsylvania, USA
Angiogenesis, antiangiogenic proteins/peptides, cancer, inflammation, COPD, and drug discovery:
Angiogenesis (new blood vessel formation) is essential for embryonic development and adult physiological functions such as wound healing, reproduction and tissue homeostasis. Abnormal angiogenesis is involved in more than 70 human diseases including cancer. To suppress cancer through inhibiting tumor angiogenesis has been actively pursued as an anticancer therapeutic approach.
In recent years, we have focused on identifying and investigating novel endogenous anti-angiogenesis proteins that contain the thrombospondin type 1 repeat domain (TSR). These endogenous proteins are not only valuable for anticancer drug development, but also important for understanding tissue homeostasis and organ function. So far, we have identified 3 novel endogenous antiangiogenic proteins: Isthmin 1 (ISM1), ADAMTS5 and ADAMTS4. We use CRISPR/Cas9 gene editing approach to generate knockout mice for functional investigations. We also study the mechanisms of action of these proteins using cultured primary human endothelial cells and various molecular and cell biology approaches.
Notably, we discovered a previously unrecognized protein trafficking pathway from late endosome to mitochondria which allows extracellular antiangiogenic proteins to reach mitochondria via endocytosis and execute apoptosis. We believe this is a fundamental protein trafficking pathway that is likely to exist in many cell types. We are currently investigating what are the key players in this protein trafficking pathway and how late endosome interact and fuse with mitochondria.
We have also extended our research into inflammation suppression and resolution. By serendipity, we discovered a novel protein suppressor that can quench cigarette-smoke induced Chronic Obstructive Pulmonary Disease (COPD) in mice. We are currently investigating the mechanism of action of this novel inflammation suppressor in COPD as well as its roles in other inflammatory lung diseases such as acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF).
We welcome talented and motivated young researchers and students to join us!
Chen, M, T. Qiu, J. Wu, Y. Yang, G. D. Wright, M. Wu, and R. Ge*. Extracellular anti-angiogenic proteins augment an endosomal protein trafficking pathway to reach mitochondria and execute apoptosis in HUVECs. Cell Death Differ., 2018 Mar 9. doi: 10.1038/s41418-018-0092-9. [Epub ahead of print] PubMed link
Tan, E., H. H. Asada, and R. Ge*. Extracellular vesicle carried Jagged-1 inhibit HUVEC sprouting in a 3D microenvironment. Angiogenesis, 2018 Mar 14. doi: 10.1007/s10456-018-9609-6. PubMed link
Venugopal S, Kao C, Chandna R, Sulochana KN, Subramanian V, Chen M, Kini RM, R. Ge*. Angio-3, a 10-residue peptide derived from human plasminogen kringle 3, suppresses tumor growth in mice via impeding both angiogenesis and vascular permeability. Angiogenesis. 2018 Apr 24. doi: 10.1007/s10456-018-9616-7. PubMed link
Kumar, S#., M. Chen#, Y. Li, F. H.S. Wong, C. W. Thiam, Md Z. Hossain, K. K. Poh, S. Hirohata, H. Ogawa, V. Angeli, and R. Ge*. Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque stability in ApoE-/- mice. Sci Rep. 6:31130, 2016. PubMed link
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 With accompanied journal Commentary
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 With accompanied journal highlight.
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.