GE RUOWEN

GE RUOWEN

GE RUOWEN

Associate Professor

Contact Information:

Department of Biological Sciences
National University of Singapore
14 Science Drive 4
Singapore 117543

ResearcherID link

Google Scholar link

Lab: Ruowen Ge Lab

 

6516 7879
6779 2486
dbsgerw@nus.edu.sg

Academic Qualifications

PhD University of Pennsylvania, USA

Research Interests

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!

Selected Recent Publications

  1. Lam, T. Y. W., N. Nguyen, H. Y. Peh, M. Shanmugasundaram, R. Chandna, J. H. Tee, C. B. Ong, M. Z. Hossain, S. Venugopal, T. Zhang, S. Xu, T. Qiu, W. T. Kong, S. Chakarov, S. Srivastava, W. Liao, J-S Kim, M. Teh, F. Ginhoux, W. S. F. Wong, and R. Ge*. ISM1 protects lung homeostasis via cell surface GRP78-mediated alveolar macrophage apoptosis. Proc. Natl. Acad. Sci. USA. 119(4):e2019161119, 2022. PubMed Link

  2. Matthews, A. A., P. L. R. Ee and R. Ge*. Developing inhaled protein therapeutics for lung diseases. Mol. Biomedicine 1:11, 2020. PubMed Link

  3. Ge* R and C Kao. Cell Surface GRP78 as a Death Receptor and an Anticancer Drug Target. Cancers 11(11), 1787, 2019. PubMed Link

  4. Kao C, Chandna R, Ghode A, Dsouza C, Chen M, Larsson A, Lim SH, Wang M, Cao Z, Zhu Y, Anand GS, R Ge*.  Proapoptotic Cyclic Peptide BC71 Targets Cell-Surface GRP78 and Functions as an Anticancer Therapeutic in Mice.  EBioMedicine 33: 22-32, 2018. PubMed Link  With accompanied journal Commentary

  5. 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. PubMed link

  6. 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 

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13.  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

  14.  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

  15. 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

  16.  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

  17.  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.

  18.  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. Biol. Chem. 280:27935-27948, 2005. PubMed link

 

Patents

  1. Ge, R and R. M. Kini, Small Peptides With Potent Anti-Angiogenic Activities. US patent No. 7,317,003, 2008.

  2. Ge, R and R. M. Kini, Small Peptides with Potent Anti-Angiogenic Activities. US patent No. 6,200,954, 2001.