Weiquan (Wendy) Zhu

Weiquan (Wendy) Zhu, PhD

Languages spoken: English, Chinese

Academic Information

Departments Primary - Ophthalmology & Visual Sciences , Adjunct - Pathology

My research interests are on vascular stability and its relationship to disease. I have a broad background in molecular biology, biochemistry, and cell biology, as well as specific expertise in signaling cascades that are required for studying essential cellular responses in vascular biology and pathology. I conducted my postdoctoral training with Dr. Dean Y. Li at the University of Utah, where I studied the function of the small GTPase ARF6 and the protective role of ARF6 inhibition in animal models of sepsis and arthritis. This work led to two first-author publications: 1) the discovery that the interleukin receptor activates a MYD88-ARNO-ARF6 cascade to disrupt vascular stability and how these effects are central to inflammatory arthritis (Nature, 2012) and 2) the first indication that Slit-Robo can serve as a target to blunt the cytokine storm associated with sepsis and influenza (Sci. Transl. Med., 2010).

As an independent investigator, I have expanded my research into new areas, such as the nexus between inflammation, infection and immune-related diseases. My laboratory’s research focuses on examining whether ARF6 activation acts as a common convergence point to regulate multiple inflammatory and angiogenic pathways and determining whether blocking ARF6 activation promotes vascular stability and can be used as a novel strategy to treat sepsis, cytokine storm related syndromes, and vascular eye disease. We published an article in The Journal of Clinical Investigation (JCI, 2017), which shows that ARF6 inhibition stabilizes the blood-retina barrier and reduces debilitating sequelae in several ocular inflammatory disease-related animal models. This work has triggered our interest in determining whether ARF6 inhibition would have similar efficacy in maintaining blood-CNS barrier (BCNSB) function under pathological conditions in CNS and in maintaining alveolar-capillary barrier function under pathological conditions of infection-induced ARDS. My long-term goal is to have these basic science discoveries translated into therapeutics that can be used in the clinic.

Research Statement

My research interests are on vascular stability and its relationship to disease. I have a broad background in molecular biology, biochemistry, and cell biology, as well as specific expertise in signaling cascades that are required for studying essential cellular responses in vascular biology and pathology. I conducted my postdoctoral training with Dr. Dean Y. Li at the University of Utah where I studied the function of the small GTPase ARF6 and the protective role of ARF6 inhibition in animal models of sepsis and arthritis. This work led to two first author publications: 1) the discovery that the interleukin receptor activates a MYD88-ARNO-ARF6 cascade to disrupt vascular stability and how these effects are central to inflammatory arthritis (Nature, 2012) and 2) the first indication that Slit-Robo can serve as a target to blunt the cytokine storm associated with sepsis and influenza (Sci. Transl. Med., 2010).

As an independent investigator, I have expanded my research into new arenas, such as the nexus between inflammation, infection, and immune-related diseases. My laboratory’s research focuses on examining whether ARF6 activation acts as a common convergence point to regulate multiple inflammatory and angiogenic pathways and determining whether blocking ARF6 activation promotes vascular stability and can be used as a novel strategy to treat sepsis, cytokine storm related syndromes, and vascular eye disease. Most recently, we discovered that ARF6 activation triggers inflammation-induced endothelial-to-mesenchymal transition (EndoMT) in the central nervous system (CNS), breaks down the blood-CNS-barrier (BCNSB), and contributes to the pathogenesis and progression of the neuroinflammatory disease multiple sclerosis (Neuron, 2022). This work has triggered our interest in determining whether ARF6 activation-induced EndoMT would also contribute to CNS fibrosis in MS or subretinal fibrosis in diabetic retinopathy.

Education History

Fellowship University of Utah
 Postdoctoral Fellow
Chinese Academy of Medical Sciences & Peking Union Medical College
 PhD

Selected Publications

Journal Article

  1. Sun Z, Zhao H, Fang D, Davis CT, Shi DS, Lei K, Rich BE, Winter JM, Guo L, Sorensen LK, Pryor RJ, Zhu N, Lu S, Dickey LL, Doty DJ, Tong Z, Thomas KR, Mueller AL, Grossmann AH, Zhang B, Lane TE, Fujinami RS, Odelberg SJ, Zhu W (2022). Neuroinflammatory disease disrupts the blood-CNS barrier via crosstalk between proinflammatory and endothelial-to-mesenchymal-transition signaling. Neuron, 110(19), 3106-3120.e7. (Read full article)
  2. Pei J, Cai L, Wang F, Xu C, Pei S, Guo H, Sun X, Chun J, Cong X, Zhu W, Zheng Z, Chen X (2022). LPA(2) Contributes to Vascular Endothelium Homeostasis and Cardiac Remodeling After Myocardial Infarction. Circ Res, 131(5), 388-403. (Read full article)
  3. Zhu X, Yang M, Zhao P, Li S, Zhang L, Huang L, Huang Y, Fei P, Yang Y, Zhang S, Xu H, Yuan Y, Zhang X, Zhu X, Ma S, Hao F, Sundaresan P, Zhu W, Yang Z (2020). Catenin α 1 mutations cause familial exudative vitreoretinopathy by overactivating Norrin/β-catenin signaling. J Clin Invest, 131(6). (Read full article)
  4. Gebremariam T, Zhang L, Alkhazraji S, Gu Y, Youssef EG, Tong Z, Kish-Trier E, Bajji A, de Araujo CV, Rich B, French SW, Li DY, Mueller AL, Odelberg SJ, Zhu W, Ibrahim AS (2020). Preserving Vascular Integrity Protects Mice against Multidrug-Resistant Gram-Negative Bacterial Infection. Antimicrob Agents Chemother, 64(8). (Read full article)
  5. Jiang W, Chen H, Tai Z, Li T, Luo L, Tong Z, Zhu W (2020). Apigenin and Ethaverine Hydrochloride Enhance Retinal Vascular Barrier In Vitro and In Vivo. Transl Vis Sci Technol, 9(6), 8. (Read full article)
  6. Xiao X, Zhuang X, Xu C, Chen H, Zhu W, Pang C, Zhang M (2020). ROBO4 deletion ameliorates PAF-mediated skin inflammation via regulating the mRNA translation efficiency of LPCAT1/LPCAT2 and the expression of PAF receptor. Int J Biol Sci, 16(6), 1086-1095. (Read full article)
  7. Gong B, Zhang H, Huang L, Chen Y, Shi Y, Tam PO, Zhu X, Huang Y, Lei B, Sundaresan P, Li X, Jiang L, Yang J, Lin Y, Lu F, Chen L, Li Y, Leung CK, Guo X, Zhang S, Huang G, Wu Y, Zhou T, Shuai P, Tham CC, Weisschuh N, Krishnadas SR, Mardin C, Reis A, Yang J, Zhang L, Zhou Y, Wang Z, Qu C, Shaw PX, Pang CP, Sun X, Zhu W, Li DY, Pasutto F, Yang Z (2019). Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis. Genet Med, 21(10), 2345-2354. (Read full article)
  8. Pan T, Sun Z, Lai X, Orozcoterwengel P, Yan P, Wu G, Wang H, Zhu W, Wu X, Zhang B (2019). Hidden species diversity in Pachyhynobius: A multiple approaches species delimitation with mitogenomes. Mol Phylogenet Evol, 137, 138-145. (Read full article)
  9. Grossmann AH, Zhao H, Jenkins N, Zhu W, Richards JR, Yoo JH, Winter JM, Rich B, Mleynek TM, Li DY, Odelberg SJ (2016). The small GTPase ARF6 regulates protein trafficking to control cellular function during development and in disease. Small GTPases, 10(1), 1-12. (Read full article)
  10. Zhu W, Shi DS, Winter JM, Rich BE, Tong Z, Sorensen LK, Zhao H, Huang Y, Tai Z, Mleynek TM, Yoo JH, Dunn C, Ling J, Bergquist JA, Richards JR, Jiang A, Lesniewski LA, Hartnett ME, Ward DM, Mueller AL, Ostanin K, Thomas KR, Odelberg SJ, Li DY (2017). Small GTPase ARF6 controls VEGFR2 trafficking and signaling in diabetic retinopathy. J Clin Invest, 127(12), 4569-4582. (Read full article)
  11. Yoo JH, Shi DS, Grossmann AH, Sorensen LK, Tong Z, Mleynek TM, Rogers A, Zhu W, Richards JR, Winter JM, Zhu J, Dunn C, Bajji A, Shenderovich M, Mueller AL, Woodman SE, Harbour JW, Thomas KR, Odelberg SJ, Ostanin K, Li DY (2016). ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma. Cancer Cell, 29(6), 889-904. (Read full article)
  12. Gibson CC, Davis CT, Zhu W, Bowman-Kirigin JA, Walker AE, Tai Z, Thomas KR, Donato AJ, Lesniewski LA, Li DY (2015). Dietary Vitamin D and Its Metabolites Non-Genomically Stabilize the Endothelium. PLoS One, 10(10), e0140370. (Read full article)
  13. Gibson CC, Zhu W, Davis CT, Bowman-Kirigin JA, Chan AC, Ling J, Walker AE, Goitre L, Delle Monache S, Retta SF, Shiu YT, Grossmann AH, Thomas KR, Donato AJ, Lesniewski LA, Whitehead KJ, Li DY (2015). Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Circulation, 131(3), 289-99. (Read full article)
  14. Davis CT, Zhu W, Gibson CC, Bowman-Kirigin JA, Sorensen L, Ling J, Sun H, Navankasattusas S, Li DY (2014). ARF6 inhibition stabilizes the vasculature and enhances survival during endotoxic shock. J Immunol, 192(12), 6045-52. (Read full article)
  15. Yu J, Zhang X, Kuzontkoski PM, Jiang S, Zhu W, Li DY, Groopman JE (2014). Slit2N and Robo4 regulate lymphangiogenesis through the VEGF-C/VEGFR-3 pathway. Cell Commun Signal, 12, 25. (Read full article)
  16. Zhu W, London NR, Gibson CC, Davis CT, Tong Z, Sorensen LK, Shi DS, Guo J, Smith MC, Grossmann AH, Thomas KR, Li DY (2012). Interleukin receptor activates a MYD88-ARNO-ARF6 cascade to disrupt vascular stability. Nature, 492(7428), 252-5. (Read full article)
  17. Sawada J, Urakami T, Li F, Urakami A, Zhu W, Fukuda M, Li DY, Ruoslahti E, Komatsu M (2012). Small GTPase R-Ras regulates integrity and functionality of tumor blood vessels. Cancer Cell, 22(2), 235-49. (Read full article)
  18. Prasad A, Kuzontkoski PM, Shrivastava A, Zhu W, Li DY, Groopman JE (2012). Slit2N/Robo1 inhibit HIV-gp120-induced migration and podosome formation in immature dendritic cells by sequestering LSP1 and WASp. PLoS One, 7(10), e48854. (Read full article)
  19. Zhang X, Yu J, Kuzontkoski PM, Zhu W, Li DY, Groopman JE (2012). Slit2/Robo4 signaling modulates HIV-1 gp120-induced lymphatic hyperpermeability. PLoS Pathog, 8(1), e1002461. (Read full article)
  20. London NR, Zhu W, Bozza FA, Smith MC, Greif DM, Sorensen LK, Chen L, Kaminoh Y, Chan AC, Passi SF, Day CW, Barnard DL, Zimmerman GA, Krasnow MA, Li DY (2010). Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and influenza. Sci Transl Med, 2(23), 23ra19. (Read full article)
  21. Jones CA, Nishiya N, London NR, Zhu W, Sorensen LK, Chan AC, Lim CJ, Chen H, Zhang Q, Schultz PG, Hayallah AM, Thomas KR, Famulok M, Zhang K, Ginsberg MH, Li DY (2009). Slit2-Robo4 signalling promotes vascular stability by blocking Arf6 activity. Nat Cell Biol, 11(11), 1325-31. (Read full article)
  22. Whitehead KJ, Chan AC, Navankasattusas S, Koh W, London NR, Ling J, Mayo AH, Drakos SG, Jones CA, Zhu W, Marchuk DA, Davis GE, Li DY (2009). The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases. Nat Med, 15(2), 177-84. (Read full article)
  23. Chen J, Chen Y, Zhu W, Han Y, Han B, Xu R, Deng L, Cai Y, Cong X, Yang Y, Hu S, Chen X (2008). Specific LPA receptor subtype mediation of LPA-induced hypertrophy of cardiac myocytes and involvement of Akt and NFkappaB signal pathways. J Cell Biochem, 103(6), 1718-31. (Read full article)
  24. Chen J, Baydoun AR, Xu R, Deng L, Liu X, Zhu W, Shi L, Cong X, Hu S, Chen X (2008). Lysophosphatidic acid protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis. Stem Cells, 26(1), 135-45. (Read full article)
  25. Chen J, Han Y, Zhu W, Ma R, Han B, Cong X, Hu S, Chen X (2006). Specific receptor subtype mediation of LPA-induced dual effects in cardiac fibroblasts. FEBS Lett, 580(19), 4737-45. (Read full article)
  26. Wang Y, Chen X, Zhu W, Zhang H, Hu S, Cong X (2006). Growth inhibition of mesenchymal stem cells by aspirin: involvement of the WNT/beta-catenin signal pathway. Clin Exp Pharmacol Physiol, 33(8), 696-701. (Read full article)
  27. Zhu W, Chen J, Cong X, Hu S, Chen X (2006). Hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells. Stem Cells, 24(2), 416-25. (Read full article)
  28. Yiquan Wang, Zhu W, Lei Huang, et al (2006). Genetic diversity of Chinese alligator (Alligator sinensis) revealed by AFLP analysis: an implication on the management. Biodivers Conserv, 2945-55.

Patent

  1. Dean Li, Nyall London, Weiquan Zhu (2012). COMPOSITIONS AND METHODS FOR PROMOTING VASCULAR BARRIER FUNCTION AND TREATING PULONARY FIBROSIS. U.S. Patent No. US20120129757 A1. Washington, D.C.:U.S. Patent and Trademark Office.
  2. Dean Y. Li, Nyall London, Weiquan Zhu (2010). Compositions and methods for promoting vascular barrier function and treating pulmonary fibrosis. U.S. Patent No. US20120129757 A1. Washington, D.C.:U.S. Patent and Trademark Office.