Rong Wang, PhD

Mildred V. Strouss Endowed Chair in Vascular Surgery, UCSF

Professor, Department of Surgery, UCSF; Director, Laboratory for Accelerated Vascular Research

Cancer Center Program Membership

Affiliate Member

Research Summary

Angiogenesis, or new blood vessel formation, plays a principal role in health and cancer. Research in my lab aims to advance the fundamental understanding of the cellular, molecular, and hemodynamic mechanisms underlying arterial venous programming in normal and tumor angiogenesis. We are well equipped to perform state-of-the-art research at the organismic, cellular, and molecular levels. Sophisticated mouse genetics allow us to delete or express genes in endothelial cells that line the vessel lumen in a lineage-specific and temporally controllable fashion. These mouse tools are enhanced with cutting-edge imaging capabilities, including 5D two-photon microscopy (3D + blood flow over time). These innovations provide us exceptional access to in vivo cell biology and gene function in both physiological and pathological angiogenesis in living animals. This basic approach is complemented by preclinical studies with our elegant mouse models of disease, offering outstanding opportunities for early translational research. With these approaches, we are investigating the molecular programming in the development of arteries in hepatocellular carcinoma (HCC), which is characterized by highly arterialized tumor masses.

We hypothesize that genes important in normal arterial programming are likely to play a role in HCC artery formation, and we intend to ultimately study the Notch pathway as a molecular regulator of HCC arterial formation. Our goal is to inhibit HCC arterial growth, block tumor blood supply, and starve cancer cells. Our investigation of the molecular regulators that govern arterial-venous programming may ultimately help identify novel drug targets and inform rational design of new therapeutics to treat major human diseases, including HCC. I have many years of experience studying HCC in mouse models, beginning with my postdoctoral research. I pioneered the liver-specific tetracycline-regulatable Met transgenic mouse model of HCC and contributed to the development of the hydrodynamic injection HCC mouse model, both currently in wide use. The combination of my expertise in HCC and my broad experience in arterial-venous programming prepare us well to investigate the effects of targeting the arterial supply of HCC.

Research Funding

  • February 1, 2020 - January 31, 2025 - Molecular Pathogenesis of Hereditary Hemorrhagic Telangiectasia , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01NS113429
  • February 1, 2020 - January 31, 2025 - Molecular Pathogenesis of Hereditary Hemorrhagic Telangiectasia , Principal Investigator . Sponsor: NINDS, Sponsor Award ID: R01NS113429
  • July 1, 2019 - June 30, 2022 - Identifying Molecular Regulators of Hereditary Hemorrhagic Telangiectasia In a Novel Mouse Model , Principal Investigator . Sponsor: American Heart Association, Sponsor Award ID: 19TPA34910134
  • July 1, 2018 - June 30, 2021 - Molecular Pathogenesis and Therapy for Critical Lim Ischemia , Principal Investigator . Sponsor: Tobacco Related Disease Research Program, Sponsor Award ID: High Impact Research Project Award

Education

Sichuan University, Chendu, China, B.Sc., 1980-84, Biology
Graduate School of Chinese Science and Technology University, Institute of Genetics, Academia Sinica, Beijing, China, M.Sc. candidate, 1984-88, Genetics
University of North Carolina at Chapel Hill, Ph.D., 1988-93, Biology (Angiogenesis)
University of California, San Francisco, Postdoctoral Fellow, 1994-2001, Cancer Biology

Honors & Awards

  • 1994-97
    Leukemia Society of America, Postdoctoral Fellowship
  • 1997-99
    American Heart Association, Postdoctoral Fellowship
  • 2003-2005
    Pfizer Atorvastatin Research Award

Selected Publications

  1. Prather BL, Ji S, Zhao Y, Shajan FJ, Zhao M, Buuh ZY, Maloney R, Zhang R, Cohen C, Wang RE. Fluorine-thiol displacement probes for acetaminophen's hepatotoxicity. Acta Pharm Sin B. 2023 Jan; 13(1):204-212.  View on PubMed
  2. Kang J, Lewis TR, Gardner A, Andrade RB, Wang RE. Semi-syntheses and interrogation of indole-substituted Aspidosperma terpenoid alkaloids. Org Biomol Chem. 2022 05 18; 20(19):3988-3997.  View on PubMed
  3. Islam MS, Junod SL, Zhang S, Buuh ZY, Guan Y, Zhao M, Kaneria KH, Kafley P, Cohen C, Maloney R, Lyu Z, Voelz VA, Yang W, Wang RE. Unprotected peptide macrocyclization and stapling via a fluorine-thiol displacement reaction. Nat Commun. 2022 01 17; 13(1):350.  View on PubMed
  4. Zhang Y, Fang C, Wang RE, Wang Y, Guo H, Guo C, Zhao L, Li S, Li X, Schultz PG, Cao YJ, Wang F. A tumor-targeted immune checkpoint blocker. Proc Natl Acad Sci U S A. 2019 08 06; 116(32):15889-15894.  View on PubMed
  5. Cuervo H, Nielsen CM, Simonetto DA, Ferrell L, Shah VH, Wang RA. Endothelial notch signaling is essential to prevent hepatic vascular malformations in mice. Hepatology. 2016 10; 64(4):1302-1316.  View on PubMed
  6. Nielsen CM, Huang L, Murphy PA, Lawton MT, Wang RA. Mouse Models of Cerebral Arteriovenous Malformation. Stroke. 2016 Jan; 47(1):293-300.  View on PubMed
  7. Murphy PA, Kim TN, Huang L, Nielsen CM, Lawton MT, Adams RH, Schaffer CB, Wang RA. Constitutively active Notch4 receptor elicits brain arteriovenous malformations through enlargement of capillary-like vessels. Proc Natl Acad Sci U S A. 2014 Dec 16; 111(50):18007-12.  View on PubMed
  8. Lin Y, Jiang W, Ng J, Jina A, Wang RA. Endothelial ephrin-B2 is essential for arterial vasodilation in mice. Microcirculation. 2014 Oct; 21(7):578-86.  View on PubMed
  9. Nielsen CM, Cuervo H, Ding VW, Kong Y, Huang EJ, Wang RA. Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice. Development. 2014 Oct; 141(19):3782-92.  View on PubMed
  10. Lindskog H, Kim YH, Jelin EB, Kong Y, Guevara-Gallardo S, Kim TN, Wang RA. Molecular identification of venous progenitors in the dorsal aorta reveals an aortic origin for the cardinal vein in mammals. Development. 2014 Mar; 141(5):1120-8.  View on PubMed
  11. Costa MJ, Wu X, Cuervo H, Srinivasan R, Bechis SK, Cheang E, Marjanovic O, Gridley T, Cvetic CA, Wang RA. Notch4 is required for tumor onset and perfusion. Vasc Cell. 2013 Apr 20; 5(1):7.  View on PubMed
  12. Kim TN, Goodwill PW, Chen Y, Conolly SM, Schaffer CB, Liepmann D, Wang RA. Line-scanning particle image velocimetry: an optical approach for quantifying a wide range of blood flow speeds in live animals. PLoS One. 2012; 7(6):e38590.  View on PubMed
  13. Murphy PA, Kim TN, Lu G, Bollen AW, Schaffer CB, Wang RA. Notch4 normalization reduces blood vessel size in arteriovenous malformations. Sci Transl Med. 2012 Jan 18; 4(117):117ra8.  View on PubMed
  14. Miniati D, Jelin EB, Ng J, Wu J, Carlson TR, Wu X, Looney MR, Wang RA. Constitutively active endothelial Notch4 causes lung arteriovenous shunts in mice. Am J Physiol Lung Cell Mol Physiol. 2010 Feb; 298(2):L169-77.  View on PubMed
  15. Herbert SP, Huisken J, Kim TN, Feldman ME, Houseman BT, Wang RA, Shokat KM, Stainier DY. Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation. Science. 2009 Oct 09; 326(5950):294-8.  View on PubMed
  16. Murphy PA, Lu G, Shiah S, Bollen AW, Wang RA. Endothelial Notch signaling is upregulated in human brain arteriovenous malformations and a mouse model of the disease. Lab Invest. 2009 Sep; 89(9):971-82.  View on PubMed
  17. Yang Y, Tang G, Yan J, Park B, Hoffman A, Tie G, Wang R, Messina LM. Cellular and molecular mechanism regulating blood flow recovery in acute versus gradual femoral artery occlusion are distinct in the mouse. J Vasc Surg. 2008 Dec; 48(6):1546-58.  View on PubMed
  18. Kim YH, Hu H, Guevara-Gallardo S, Lam MT, Fong SY, Wang RA. Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis. Development. 2008 Nov; 135(22):3755-64.  View on PubMed
  19. Murphy PA, Lam MT, Wu X, Kim TN, Vartanian SM, Bollen AW, Carlson TR, Wang RA. Endothelial Notch4 signaling induces hallmarks of brain arteriovenous malformations in mice. Proc Natl Acad Sci U S A. 2008 Aug 05; 105(31):10901-6.  View on PubMed
  20. Dubois NC, Adolphe C, Ehninger A, Wang RA, Robertson EJ, Trumpp A. Placental rescue reveals a sole requirement for c-Myc in embryonic erythroblast survival and hematopoietic stem cell function. Development. 2008 Aug; 135(14):2455-65.  View on PubMed

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