Associate Professor in Residence, Department of Surgery, UCSF; and Director, Laboratory for Accelerated Vascular Research
Mildred V. Strouss Endowed Chair in Vascular Surgery, UCSF
Research SummaryAngiogenesis, 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.
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
Graduate Research Assistant, Dr. Victoria L. Bautch, Department of Biology, University of North Carolina at Chapel Hill
Postdoctoral Fellow, J. Michael Bishop, G.W. Hooper Laboratory, UCSF
Assistant Professor, Surgery and Anatomy, UCSF
Director, Laboratory for Accelerated Vascular Research, UCSF
Mildred V. Strouss Endowed Chair in Vascular Surgery
Associate Professor, Anatomy, UCSF
Associate Professor, Surgery, UCSF
Honors & Awards
Leukemia Society of America, Postdoctoral Fellowship
American Heart Association, Postdoctoral Fellowship
Pfizer Atorvastatin Research Award
- Dubois, NA, LC Kolpack, R Wang, RG Azizkhan and VL Bautch. Isolation and characterization of an established endothelial cell line from transgenic mouse hemangiomas. Exp Cell Res, 1991 196(2): 302-13.
- Wang, R and VL Bautch. The polyomavirus early region gene in transgenic mice causes vascular and bone tumors. J Virol, 1991 65(10): 5174-83.
- Wang, R, R Clark and VL Bautch. Embryonic stem cell-derived cystic embryoid bodies form vascular channels: an in vitro model of blood vessel development. Development, 1992 114(2): 303-16.
- Wang, R, GP Siegal, DL Scott and VL Bautch. Developmental analysis of bone tumors in polyomavirus transgenic mice. Lab Invest, 1994 70(1): 86-94.
- Wang, R, R Kobayashi and JM Bishop. Cellular adherence elicits ligand-independent activation of the Met cell-surface receptor. Proc Natl Acad Sci U S A, 1996 93(16): 8425-30.
- Wang, R, LD Ferrell, S Faouzi, JJ Maher and JM Bishop. Activation of the Met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice. J Cell Biol, 2001 153(5): 1023-34.
- Chang, DS, H Su, GL Tang, LS Brevetti, R Sarkar, R Wang, YW Kan and LM Messina. Adeno-associated viral vector- mediated gene transfer of VEGF normalizes skeletal muscle oxygen tension and induces arteriogenesis in ischemic rat hindlimb. Mol Ther, 2003 7(1): 44-51.
- Tang, G, DN Charo, R Wang, IF Charo and L Messina. CCR2-/- knockout mice revascularize normally in response to severe hindlimb ischemia. J Vasc Surg, 2004 40(4): 786-95.
- Tang, GL, DS Chang, R Sarkar, R Wang and LM Messina. The effect of gradual or acute arterial occlusion on skeletal muscle blood flow, arteriogenesis, and inflammation in rat hindlimb ischemia. J Vasc Surg, 2005 41(2): 312-20.
- Yan, J, GL Tang, R Wang and LM Messina. Optimization of Adenovirus-mediated endothelial nitric oxide synthase delivery in rat hindlimb ischemia. Gene Therapy, 2005 12(22):1640-50.
- Carpenter, B, Y Lin, S Stoll, RL Raffai, R McCuskey and R Wang. VEGF is crucial for the hepatic vascular development required for lipoprotein uptake. Development, 2005 132(14): 3293-303.
- Carlson, TR, Y Yan, X Wu, MT Lam, GL Tang, LJ Beverly, LM Messina, AJ Capobianco, Z Werb and R Wang. Endothelial expression of constitutively active Notch4 elicits reversible arteriovenous malformations in adult mice. Proc Natl Acad Sci U S A, 2005 102(28): 9884-9.
- Proctor, JM, K Zang, D Wang, R Wang and LF Reichardt. Vascular Development of the Brain Requires beta8 Integrin Expression in the Neuroepithelium. J Neurosci, 2005 25(43): 9940-8.
- Braren, R, H Hu, YH Kim, H Beggs, LF Reichardt and R Wang. Endothelial FAK is essential for vascular network stability by regulating lamellipodial formation and cell survival. J Cell Biol, 2006 176(1): 151-162.
- Tward, AD, KD Jones, S Yant, ST Cheung, ST Fan, X Chen, MA Kay, R Wang, JM Bishop. Distinct pathways of genomic progression to benign and malignant tumors of the liver. Proc Natl Acad Sci U S A, 2007 104(37):14771- 14776.
- Carlson, TR, H Hu, R Braren, YH Kim, and RA Wang. Cell-autonomous requirement for β1 integrin in endothelial cell adhesion, migration, and survival during angiogenesis in mice. Development, 2008 135(12):2193-202 (PMC2582018).
- He, C, H Hu, R Braren, S-Y Fong, A Trumpp, TR Carlson, and RA Wang. c-myc in the hematopoetic lineage is crucial for its angiogenic function in the mouse embryo. Development, 2008 135(14):2467-77 (PMC2597486).
- Dubois, NC, C Adolphe, A Ehninger, RA Wang, EJ Robertson, and A Trumpp. Placental rescue reveals a sole requirement for C-Myc in embryonic erythroblast survival and hematopoietic stem cell function. Development, 2008 135(14):2455-65.
- Murphy, PA, MTY Lam, X Wu, TN Kim, SM Vartanian, AW Bollen, TR Carlson, and RA Wang. Endothelial Notch4 signaling induces hallmarks of brain arteriovenous malformations in mice. Proc Natl Acad Sci U S A, 2008 105(31):10901-10906 (PMC2504798).
- Kim, YH, H Hu, S Guevara-Gallardo, MTY Lam, S-Y Fong, and RA Wang. Artery and vein size is balanced by Notch and ephrinB2/EphB4 during angiogenesis. Development, 2008 135(22):3755-3764 (PMC2596923).
- Murphy, PA, G Lu, S Shiah, AW Bollen, and RA Wang. Endothelial Notch signaling is upregulated in human brainarteriovenous malformations and a mouse model of the disease. Lab Invest, 2009 89(9):971-82.
- Herbert, SP, J Huisken, TN Kim, ME Feldman, BT Houseman, RA Wang, KM Shokat, and DYR Stainier. Arterial/Venous Segregation by Selective Cell Sprouting: An Alternative Mode of Blood Vessel Formation. Science, 2009 326(5950):294-8.
- Miniati, D, EB Jelin, J Ng, J Wu, TR Carlson, X Wu, MR Looney, RA Wang. Constitutively active endothelial Notch4causes lung arteriovenous shunts in mice. Am J Physiol Lung Cell Mol Physiol, 2010 298(2):L169-77 (PMC2822562).
- Clever, JL, Y Sakai, RA Wang, and DB Schneider. Inefficient skeletal muscle repair in inhibitor of differentiation (Id)knockout mice suggests a crucial role for BMP signaling during adult muscle regeneration. Am J Physiol Cell Physiol, 2010, 298(5):C1087-99 (PMC2867391).