Home > People > Rong Wang, PhD

Rong Wang, PhD

Professor
Surgery
Address: 
513 Parnassus Avenue, HSW, Rm 1618
UCSF Box 0222
San Francisco, CA 94143
United States
Research Interests: 
Arterial-venous programming in development, aging, regeneration, and disease

Research Summary:
Research in my lab is focused on angiogenesis, or new blood vessel formation, which is a critical process in development and disease. My lab aims to advance the fundamental understanding of the cellular, molecular, and hemodynamic mechanisms underlying arterial-venous programming in normal and pathological angiogenesis. We use cutting-edge mouse genetics to delete or express genes in a cell lineage-specific and temporally controllable fashion in endothelial cells. This advance is crucial for the study of candidate genes in vascular function, especially when combined with sophisticated 5D two-photon imaging (3D + blood flow over time). These innovative approaches provide us with exceptional access to gene function in both healthy and pathological conditions in living animals. This basic approach is complemented by preclinical studies with patient samples in addition to our mouse models of disease. In particular, we investigate the molecular regulators governing arterial-venous programming – particularly the Notch, ephrin-B2, and TGF-beta signaling pathways – in both normal and pathological conditions.

 

Ongoing projects:

Vascular Development.  Our lab aims to identify molecular regulators of arterial and venous cell fate determination and morphogenesis in embryonic development. We primarily focus on the origin and morphogenesis of the dorsal aorta and cardinal vein, the first major artery-vein pair to form in the body.

Arteriovenous Malformation (AVM).  AVMs are severe vascular anomalies that shunt blood directly from arteries to veins, displace intervening capillaries, and bypass tissues. My lab studies the pathogenesis and regression of AVMs. We have a long history of investigation using animal models into Notch-mediated AVM pathogenesis as well as into potential treatments for the disease.

Arterial occlusive diseases and arteriogenesis.  The body responds to arterial occlusions by inducing arteriogenesis, or radial enlargement of arteries, to restore circulation to blood-deprived tissue. We are investigating pro-arteriogenic molecular regulators to uncover potential therapeutic targets, which may be used to enhance the body’s natural defense against arterial occlusive disease.

Cancer. Solid tumors induce arteriogenesis to support their growth. We investigate the molecular stimulators of arteriogenesis in tumor progression and regression, particularly in hepatocellular carcinoma (HCC), which is characterized by large and highly arterialized tumor masses in the liver. We study genes regulating tumor arterial growth and modify these genes to target tumor arterial supply and to inhibit HCC growth.

Ultimately, through these distinct but interconnected fields of study, we hope to identify novel drug targets and inform rational design of new therapeutics to treat human disease.

Publications: 

Molecular dynamics model of mechanophore sensors for biological force measurement.

Heliyon

Mittal S, Wang RE, Ros R, Ondrus AE, Singharoy A

Flexible Fluorine-Thiol Displacement Stapled Peptides with Enhanced Membrane Penetration for the Estrogen Receptor/Coactivator Interaction.

The Journal of biological chemistry

Maloney R, Junod SL, Hagen KM, Lewis T, Cheng C, Shajan FJ, Zhao M, Moore TW, Truong TH, Yang W, Wang RE

Meeting Proceedings from ICBS 2022 - Uncovering Solutions for Diseases.

ACS chemical biology

Syphers JL, Xue L, Yi X, Wang RE, Haubrich BA

Nitric oxide synthase and reduced arterial tone contribute to arteriovenous malformation.

Science advances

Huang L, Cheng F, Zhang X, Zielonka J, Nystoriak MA, Xiang W, Raygor K, Wang S, Lakshmanan A, Jiang W, Yuan S, Hou KS, Zhang J, Wang X, Syed AU, Juric M, Takahashi T, Navedo MF, Wang RA

Monitoring of cell-cell communication and contact history in mammals.

Science (New York, N.Y.)

Zhang S, Zhao H, Liu Z, Liu K, Zhu H, Pu W, He L, Wang RA, Zhou B

Endothelial Rbpj deletion normalizes Notch4-induced brain arteriovenous malformation in mice.

The Journal of experimental medicine

Nielsen CM, Zhang X, Raygor K, Wang S, Bollen AW, Wang RA

Mechanical Stretch Increases Expression of CXCL1 in Liver Sinusoidal Endothelial Cells to Recruit Neutrophils, Generate Sinusoidal Microthombi, and Promote Portal Hypertension.

Gastroenterology

Hilscher MB, Sehrawat T, Arab JP, Zeng Z, Gao J, Liu M, Kostallari E, Gao Y, Simonetto DA, Yaqoob U, Cao S, Revzin A, Beyder A, Wang RA, Kamath PS, Kubes P, Shah VH

Abnormal arterial-venous fusions and fate specification in mouse embryos lacking blood flow.

Scientific reports

Hwa JJ, Beckouche N, Huang L, Kram Y, Lindskog H, Wang RA

Endothelial notch signaling is essential to prevent hepatic vascular malformations in mice.

Hepatology (Baltimore, Md.)

Cuervo H, Nielsen CM, Simonetto DA, Ferrell L, Shah VH, Wang RA

Mouse Models of Cerebral Arteriovenous Malformation.

Stroke

Nielsen CM, Huang L, Murphy PA, Lawton MT, Wang RA

Constitutively active Notch4 receptor elicits brain arteriovenous malformations through enlargement of capillary-like vessels.

Proceedings of the National Academy of Sciences of the United States of America

Murphy PA, Kim TN, Huang L, Nielsen CM, Lawton MT, Adams RH, Schaffer CB, Wang RA

Endothelial ephrin-B2 is essential for arterial vasodilation in mice.

Microcirculation (New York, N.Y. : 1994)

Lin Y, Jiang W, Ng J, Jina A, Wang RA

Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice.

Development (Cambridge, England)

Nielsen CM, Cuervo H, Ding VW, Kong Y, Huang EJ, Wang RA

Molecular identification of venous progenitors in the dorsal aorta reveals an aortic origin for the cardinal vein in mammals.

Development (Cambridge, England)

Lindskog H, Kim YH, Jelin EB, Kong Y, Guevara-Gallardo S, Kim TN, Wang RA

Notch4 is required for tumor onset and perfusion.

Vascular cell

Costa MJ, Wu X, Cuervo H, Srinivasan R, Bechis SK, Cheang E, Marjanovic O, Gridley T, Cvetic CA, Wang RA

Notch4 normalization reduces blood vessel size in arteriovenous malformations.

Science translational medicine

Murphy PA, Kim TN, Lu G, Bollen AW, Schaffer CB, Wang RA

Constitutively active endothelial Notch4 causes lung arteriovenous shunts in mice.

American journal of physiology. Lung cellular and molecular physiology

Miniati D, Jelin EB, Ng J, Wu J, Carlson TR, Wu X, Looney MR, Wang RA

Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation.

Science (New York, N.Y.)

Herbert SP, Huisken J, Kim TN, Feldman ME, Houseman BT, Wang RA, Shokat KM, Stainier DY

Endothelial Notch signaling is upregulated in human brain arteriovenous malformations and a mouse model of the disease.

Laboratory investigation; a journal of technical methods and pathology

Murphy PA, Lu G, Shiah S, Bollen AW, Wang RA

Cellular and molecular mechanism regulating blood flow recovery in acute versus gradual femoral artery occlusion are distinct in the mouse.

Journal of vascular surgery

Yang Y, Tang G, Yan J, Park B, Hoffman A, Tie G, Wang R, Messina LM

Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis.

Development (Cambridge, England)

Kim YH, Hu H, Guevara-Gallardo S, Lam MT, Fong SY, Wang RA

Endothelial Notch4 signaling induces hallmarks of brain arteriovenous malformations in mice.

Proceedings of the National Academy of Sciences of the United States of America

Murphy PA, Lam MT, Wu X, Kim TN, Vartanian SM, Bollen AW, Carlson TR, Wang RA

Placental rescue reveals a sole requirement for c-Myc in embryonic erythroblast survival and hematopoietic stem cell function.

Development (Cambridge, England)

Dubois NC, Adolphe C, Ehninger A, Wang RA, Robertson EJ, Trumpp A

c-myc in the hematopoietic lineage is crucial for its angiogenic function in the mouse embryo.

Development (Cambridge, England)

He C, Hu H, Braren R, Fong SY, Trumpp A, Carlson TR, Wang RA

Distinct pathways of genomic progression to benign and malignant tumors of the liver.

Proceedings of the National Academy of Sciences of the United States of America

Tward AD, Jones KD, Yant S, Cheung ST, Fan ST, Chen X, Kay MA, Wang R, Bishop JM

Endothelial FAK is essential for vascular network stability, cell survival, and lamellipodial formation.

The Journal of Cell Biology

Braren R, Hu H, Kim YH, Beggs HE, Reichardt LF, Wang R

Vascular development of the brain requires beta8 integrin expression in the neuroepithelium.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Proctor JM, Zang K, Wang D, Wang R, Reichardt LF

Endothelial expression of constitutively active Notch4 elicits reversible arteriovenous malformations in adult mice.

Proceedings of the National Academy of Sciences of the United States of America

Carlson TR, Yan Y, Wu X, Lam MT, Tang GL, Beverly LJ, Messina LM, Capobianco AJ, Werb Z, Wang R

VEGF is crucial for the hepatic vascular development required for lipoprotein uptake.

Development (Cambridge, England)

Carpenter B, Lin Y, Stoll S, Raffai RL, McCuskey R, Wang R

Genomic progression in mouse models for liver tumors.

Cold Spring Harbor symposia on quantitative biology

Tward AD, Jones KD, Yant S, Kay MA, Wang R, Bishop JM

CCR2-/- knockout mice revascularize normally in response to severe hindlimb ischemia.

Journal of vascular surgery

Tang G, Charo DN, Wang R, Charo IF, Messina L

Adeno-associated viral vector-mediated gene transfer of VEGF normalizes skeletal muscle oxygen tension and induces arteriogenesis in ischemic rat hindlimb.

Molecular therapy : the journal of the American Society of Gene Therapy

Chang DS, Su H, Tang GL, Brevetti LS, Sarkar R, Wang R, Kan YW, Messina LM

Activation of the Met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice.

The Journal of Cell Biology

Wang R, Ferrell LD, Faouzi S, Maher JJ, Bishop JM

European surveillance of infections and risk factors in cancer patients.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology

Buchheidt D, Hiddemann W, Schiel X, Kremery V, Karthaus M, Donnelly JP, Wilhelm M, Maschmeyer G, Link H, Adam D, Helmerking M

Cellular adherence elicits ligand-independent activation of the Met cell-surface receptor.

Proceedings of the National Academy of Sciences of the United States of America

Wang R, Kobayashi R, Bishop JM

Developmental analysis of bone tumors in polyomavirus transgenic mice.

Laboratory investigation; a journal of technical methods and pathology

Wang R, Siegal GP, Scott DL, Bautch VL

Isolation and characterization of an established endothelial cell line from transgenic mouse hemangiomas.

Experimental cell research

Dubois NA, Kolpack LC, Wang R, Azizkhan RG, Bautch VL

Faculty Type: 
Core CVRI Faculty