Rong Wang, PhD
Professor
Surgery
School of Medicine

Proper formation and function of the vasculature are crucial for health and survival, as the vasculature supplies all cells in the body. A dysfunctional vasculature causes myriad diseases, including stroke, arterial occlusive diseases, and vascular anomalies. Our long-term goal is to identify novel drug targets and inform rational therapeutic designs to treat vascular diseases. Our strategy is to understand genes crucial for angiogenesis (new vessel formation) in the normal and diseased states, concentrating on the Notch, ephrin-B2, and TGF-beta pathways. We employ cutting-edge mouse genetics to delete or express genes in a cell lineage-specific and temporally controllable fashion in vascular cells. We combine these molecular approaches with mouse models of diseases as well as live 5D two-photon imaging (3D + blood flow over time) to uncover both the molecular mechanisms and hemodynamic signals in development and disease progression. These preclinical animal studies are coupled with patient sample validations. Our lab members come from diverse fields, including biology, bioengineering, and medicine, creating a collaborative and exciting environment. We strive to advance multiple projects across disciplines.

PROJECTS Molecular programming of blood vessels: Building on our study of the developing dorsal aorta and cardinal vein, the first major artery-vein (AV) pair to form in the body, our lab aims to identify molecular regulators that program arteries and veins in vital organs during development and aging. We examine the interplay between genetic AV programming and flow-induced patterning. Understanding AV programming in normal angiogenesis provides important insights into how the genetic pathways can be hijacked in various disease states.

Stroke: We study two types of stroke, ischemic stroke and hemorrhagic stroke. Ischemic stroke occurs when arteries supplying the brain are blocked. Using a surgical model of ischemic stroke, we aim to identify technologies enabling better recover following arterial blockade. Hemorrhagic stroke, on the other hand, occurs when diseased blood vessels rupture. Brain arteriovenous malformations (AVMs), which are direct connections from arteries to veins, are one of the major causes of hemorrhagic stroke. We investigate AV programming in both AVM progression and regression.

Arteriovenous malformations: AVMs can occur anywhere in the body and comprise a category of hard to treat vascular anomalies. Most AVMs are sporadic, thus limiting the understanding of their etiology. In contrast, hereditary AVMs, such as those found in hereditary hemorrhagic telangiectasia (HHT) patients, offer an excellent opportunity to study how AVMs form. HHTs are caused by mutations in genes of the TGF-beta superfamily. We are interested in the molecular mechanisms underlying HHT-mediated AVMs formation.

Arterial occlusive diseases: Arterial occlusive diseases occur when the arteries in the body are blocked, causing insufficient blood flow to the tissues. Blockage of arteries in the brain causes stroke, in the heart causes myocardial infarction, and in the extremities causes peripheral arterial disease. Arteriogenesis, a process by which small dormant arteries around the blockage enlarge to form collateral circulation, holds promise to restore blood flow and rescue affected tissues. We investigate pro-arteriogenic molecular regulators to uncover potential therapeutic strategies to enhance the body’s natural defense against arterial occlusive disease.

• Endothelial Rbpj deletion normalizes Notch4-induced brain arteriovenous malformation in mice.
  The Journal of experimental medicine 2022 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 2019 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 2017 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.) 2016 Cuervo H, Nielsen CM, Simonetto DA, Ferrell L, Shah VH, Wang RA
• Mouse Models of Cerebral Arteriovenous Malformation.
  Stroke 2015 Nielsen CM, Huang L, Murphy PA, Lawton MT, Wang RA
• Endothelial ephrin-B2 is essential for arterial vasodilation in mice.
  Microcirculation (New York, N.Y. : 1994) 2014 Lin Y, Jiang W, Ng J, Jina A, Wang RA
• Notch4 is required for tumor onset and perfusion.
  Vascular cell 2013 Costa MJ, Wu X, Cuervo H, Srinivasan R, Bechis SK, Cheang E, Marjanovic O, Gridley T, Cvetic CA, 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 Kim TN, Goodwill PW, Chen Y, Conolly SM, Schaffer CB, Liepmann D, Wang RA
• Notch4 normalization reduces blood vessel size in arteriovenous malformations.
  Science translational medicine 2012 Murphy PA, Kim TN, Lu G, Bollen AW, Schaffer CB, Wang RA
• Inefficient skeletal muscle repair in inhibitor of differentiation knockout mice suggests a crucial role for BMP signaling during adult muscle regeneration.
  American journal of physiology. Cell physiology 2010 Clever JL, Sakai Y, Wang RA, Schneider DB
• Constitutively active endothelial Notch4 causes lung arteriovenous shunts in mice.
  American journal of physiology. Lung cellular and molecular physiology 2009 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.) 2009 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 2009 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 2008 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) 2008 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 2008 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) 2008 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) 2008 He C, Hu H, Braren R, Fong SY, Trumpp A, Carlson TR, Wang RA
• Cell-autonomous requirement for beta1 integrin in endothelial cell adhesion, migration and survival during angiogenesis in mice.
  Development (Cambridge, England) 2008 Carlson TR, Hu H, Braren R, Kim YH, 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 2007 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 2006 Braren R, Hu H, Kim YH, Beggs HE, Reichardt LF, Wang R
• Optimization of adenovirus-mediated endothelial nitric oxide synthase delivery in rat hindlimb ischemia.
  Gene therapy 2005 Yan J, Tang GL, Wang R, Messina LM
• Vascular development of the brain requires beta8 integrin expression in the neuroepithelium.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2005 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 2005 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) 2005 Carpenter B, Lin Y, Stoll S, Raffai RL, McCuskey R, Wang R
• The effect of gradual or acute arterial occlusion on skeletal muscle blood flow, arteriogenesis, and inflammation in rat hindlimb ischemia.
  Journal of vascular surgery 2005 Tang GL, Chang DS, Sarkar R, Wang R, Messina LM
• Genomic progression in mouse models for liver tumors.
  Cold Spring Harbor symposia on quantitative biology 2005 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 2004 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 2003 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 2001 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 1999 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 1996 Wang R, Kobayashi R, Bishop JM
• Developmental analysis of bone tumors in polyomavirus transgenic mice.
  Laboratory investigation; a journal of technical methods and pathology 1994 Wang R, Siegal GP, Scott DL, Bautch VL
• Embryonic stem cell-derived cystic embryoid bodies form vascular channels: an in vitro model of blood vessel development.
  Development (Cambridge, England) 1992 Wang R, Clark R, Bautch VL
• Isolation and characterization of an established endothelial cell line from transgenic mouse hemangiomas.
  Experimental cell research 1991 Dubois NA, Kolpack LC, Wang R, Azizkhan RG, Bautch VL
• The polyomavirus early region gene in transgenic mice causes vascular and bone tumors.
  Journal of virology 1991 Wang R, Bautch VL