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Wei Li

Wei Li, MD, PhD
Associate Professor

Research Interest

I am a cardiovascular biologist and I have expertise in studying vascular biology, platelet biology and thrombosis as well as heart failure.  My current research is mainly focusing on exploring the role of thymidine phosphorylase (TYMP), also known as platelet-derived endothelial cell growth factor, in the development of chronic diseases including atherosclerosis, thrombosis, and metabolic disorders.  Our recent study published by Circulation Research revealed for the first time that TYMP is a signaling molecule and participates in platelet activation and enhances thrombosis.  Most importantly, TYMP deficiency or inhibition of TYMP activity do not cause bleeding side effect in mice.  These exciting findings suggest that modulation of TYMP can potentially become a novel and systemically safe anti-platelet and anti-thrombotic therapy.  Currently, I am exploring the detailed mechanisms regarding how TYMP affects platelet function and how it affects development of diseases.  In addition to modern cell biology and molecular biology techniques, my lab has established several animal models. These include, but are not limited to, intravital microscopy-based FeCl3-induced thrombosis models, guidewire-induced carotid artery injury model, and ischemia/reperfusion models.  My long-term goal is to develop novel therapeutics for the life-threatening atherosclerotic and thrombotic cardiovascular diseases.

  1. Yang M, Cooley BC, Li W, Chen YL, Vasquez-Vivar J, Scoggins NO, Cameron SJ, Morrell CN, Silverstein RL. Platelet CD36 Promotes Thrombosis by Activating Redox Sensor BMK1/ERK5 in Hyperlipidemic Conditions. Blood. 2017; 129:2917-2927. doi: 10.1182/blood-2016-11-750133.
  2. Pawlowski CL, Li W, Ravichandran K, Sun M, Kos C, Kaur G, and Sen Gupta A. Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis. Biomaterials. 2017; 128:94-108. doi: 10.1016/j.biomaterials.2017.03.012.
  3. Shukla M, Sekhon UD, Betapudi V, Li W, Hickman DA, Pawlowski CL, Dyer MR, Neal MD, McCrae KR, and Sen Gupta A. In vitro characterization of SynthoPlate™ (synthetic platelet) technology and its in vivo evaluation in severely thrombocytopenic mice. J Thromb Haemost. 2017; 15:375-387. doi: 10.1111/jth.13579.
  4. Li W (Corresponding author), Nieman M, and Sen Gupta A. Ferric chloride-induced murine thrombosis models. Vis. Exp. 2016; 115: e54479. doi:10.3791/54479.
  5. Gupta N, Li W, and McIntyre T M. Deubiquitinases modulate platelet proteome ubiquitination, aggregation, and thrombosis. Arterioscler Thromb Vasc Biol. 2015; 35:2657-66. doi:10.1161/ATVBAHA.115.306054.
    (An Editorial comments about this paper was published in Arterioscler Thromb Vasc Biol. 2015; 35: 2489-2490)
  6. Li W (Corresponding author), & McIntyre TM. Platelet-activating factor receptor affects food intake and body weight. Genes Dis., 2015; 2:255-260. Available online 24 June. doi:10.1016/j.gendis.2015.06.002.
  7. Yao B, Wang Q, Liu CF, Bhattaram P, Li W, Mead TJ, Crish JF, Lefebvre V. The SOX9 upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers. Nucleic Acids Res. 2015; 43:5394-408. (PMC4477657)
  8. Li W (Corresponding author), Gigante A, Perez-Perez MJ, Yue H, Hirano M, McIntyre T and Silverstein RL. Thymidine phosphorylase participates in platelet signaling and promotes thrombosis. Circ Res. 2014;115:997-1006 (PMC4258140)
    (This paper was highlighted by the editor in Circulation Research "In This Issue" Anthology, Circ. Res. 2015; 117:e92-e120,)
  9. Srikanthan S, Li W, Silverstein RL, and McIntyre TM. Exosome poly-ubiquitin inhibits platelet activation, downregulates CD36, and inhibits pro-atherothombotic cellular functions. J Thromb Haemost. 2014;12:1906-1917. (PMC4229405)
  10. Gupta N, Li W, Willard B, Silverstein RL, and McIntyre T M. Proteasome proteolysis supports stimulated platelet function and thrombosis. Arterioscler Thromb Vasc Biol. 2014; 34:160-8. (PMC4059534)
  11. Brown GT, Narayanan P, Li W, Brady E, Silverstein RL, and McIntyre TM. Lipopolysaccharide stimulates platelets through an IL-1β autocrine loop. J Immunol. 2013; 191:5196-5203.
  12. Rahaman SO, Li W, and Silverstein RL. Vav guanine nucleotide exchange factors regulate atherosclerotic lesion development in mice. Arterioscler Thromb Vasc Biol. 2013; 33:2053-7.
  13. Klenotic PA, Page RC, Li W, Amick J, Misra S and Silverstein RL. Molecular basis of anti-angiogenic thrombospondin-1 type 1 repeat domain interactions with CD36. Arterioscler Thromb Vasc Biol. 2013; 33:1655-62.
  14. Li W (Corresponding author), McIntyre TM and Silverstein RL. Ferric chloride-induced murine carotid arterial thrombosis model: a model of redox pathology. Redox biology. 2013; 1:50–55.
  15. Liu JB, Li W, Chen R, and McIntyre TM. Circulating Biologically Active Oxidized Phospholipids Show On-going and Increased Oxidative Stress in Older Male Mice. Redox biology. 2013; 1:110–114.
  16. Li W. Invited commentary (Corresponding author) for “Bone Morphogenic Protein-4 Contributes to Venous Endothelial Dysfunction in Diabetic Patients Undergoing Coronary Revascularization”. Ann Thorac Surg. 2013; 95:1339.
  17. Kwon TH; Han YH; Hong SG; Lee DJ; Ha HL; Kang SW; Li W; Yoon DY. Reactive oxygen species mediated DNA damage is essential for abnormal erythropoiesis in peroxiredoxin II(-/-) mice. Biochem Biophys Res Commun. 2012;424:189-195.
  18. Yue H, Tanaka K, Furukawa T, Karnik SS, and Li W (Corresponding author). Thymidine phosphorylase inhibits rat vascular smooth muscle cell proliferation via unphosphorylated STAT3. Biochim Biophys Acta. 2012; 1823: 1316–1323.
  19. Zhu WF, Li W, Silverstein RL. Advanced glycation end products induce a prothrombotic phenotype in mice via interaction with platelet CD36. Blood. 2012; 119:6136-44.
  20. Chen K, Li W, Major J, Rahaman O, Febbraio M, and Silverstein RL. Vav guanine nucleotide exchange factors link hyperlipidemia and a prothrombotic state. Blood. 2011; 117:5744-50.
  21. Li W, Febbraio M, Reddy SP, Yu DY, Yamamoto M, and Silverstein RL. CD36 participates in a signaling pathway that regulates ROS formation in murine VSMCs. J Clin Invest. 2010; 120:3996-4006.
  22. Silverstein RL, Li W, Park YM and Rahaman SO. Mechanisms of cell signaling by the scavenger receptor CD36: implications in atherosclerosis and thrombosis. Trans Am Clin Climatol Assoc. 2010; 121:206-20.
  23. Yue H, Li W, Desnoyer R, Karnik SS. Role of nuclear unphosphorylated STAT3 in angiotensin II type 1 receptor-induced cardiac hypertrophy. Cardiovasc Res. 2010; 85:90-99.
  24. Robertson JO, Li W, Silverstein RL, Topol EJ, Smith JD. Deficiency of LRP8 in mice is associated with altered platelet function and prolonged time for in vivo thrombosis. Res. 2009; 123:644-52.
  25. Ghosh A, Li W (Co-First Author), Febbraio M, Espinola GR, Silverstein RL. Platelet CD36 mediates interactions with endothelial cell-derived microparticles and contributes to thrombosis in mice. J Clin Invest. 2008; 118:1934-43.
  26. Chen K, Febbraio M, Li W, Silverstein RL. A specific CD36-dependent signaling pathway is required for platelet activation by oxidized low-density lipoprotein. Circ Res, 2008; 102:1512-9.
  27. Handa M, Li W (Corresponding author), Morioka K, Takamori A, Yamada N, Ihaya A. Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft. J Vas Surg. 2008; 48:1566-74.
    (I mentored and directed Dr. Handa for his graduate research. This paper is his thesis)
  28. Li W (Corresponding author), Tanaka K, Morioka K, Handa M, Takamori A, Yamada N, Tanabe S, and Ihaya A. Long-term effect of gene therapy for chronic myocardial ischemia using platelet-derived endothelial cell growth factor. J Gene Med. 2008; 10:412-20.
  29. Li W (Corresponding author), Silverstein RL. Biological Surgery---Synergetic angiogenic therapy using coadministration of two progenitor cell populations. Circ Res. 2008; 103: 684-6.
    (Editorial comment to Foubert P, Matrone G, Souttou B, et al. Coadministration of endothelial and smooth muscle progenitor cells enhances the efficiency of proangiogenic cell-based therapy. Circ Res. 2008; 103(7): 751-60.)
  30. Yamada N, Li W, Ihaya A, Kimura T, Morioka K, Uesaka T, Takamori A, Handa M, Tanabe S, Tanaka K. Platelet-derived endothelial cell growth factor gene therapy for limb ischemia. J Vasc Surg. 2006; 44:1322-8.
  31. Tanabe S, Tanaka K, Ihaya A, Morioka K, Uesaka T, Li W, Yamada N, Takamori A, Handa M, and Imamura Y. Surgical Treatment for Infective Endocarditis in a Case with Bicupid Aortic Valve and Dilated Ascending Aorta. J. Cardiovasc. Surg, 2006; 35:183-187. (Manuscript in Japanese)
  32. Uesaka T, Tanaka K, Morioka K, Li W, Yamada N, Takamori A, Handa M, Tanabe S, Ihaya A, Sasaki M. Surgical strategy for critical aortic stenosis with small aortic annulus in the elderly patients. Kyobu Geka. 2006; 59:181-6. (Manuscript in Japanese)
  33. Ihaya A, Takamori A, Morioka M, Sasaki M, Yamada N, Tanabe S, Li W, Tanaka K. Popliteal artery disruption following complete dislocation of the knee. Chirurgia, 2006; 19: 219-221.
  34. Ihaya A, Tanaka K, Uesaka T, Tanaka S, Morioka K, Yamada N, Li W, Sasaki M, Takamori A, Handa M, Tanabe S, Nisijima K, Utinami Y, Shukunami K, Kotuji F, Otsuki S. One case report of maternal deep vein thrombosis in the early stage of pregnancy caused by deficiency of protein S-Perinatal care using Caprosin. Perinatal Medicine, 2006; 36: 787-790. (Manuscript in Japanese)
  35. Morioka K, Tanaka K, Li W, Tanabe S, Yamada N, and Ihaya A. A Case of Myonephropathic Metabolic Syndrome Caused by Aortic Saddle Embolus Originating from a Left Atrial Myxoma. J. Vasc. Surg. 2006; 15:15-19. (Manuscript in Japanese)
  36. Li W, Tanaka K, Morioka K, Uesaka T, Yamada N, Takamori A, Handa M, Tanabe S, and Ihaya A. Thymidine phosphorylase gene transfer inhibits vascular smooth muscle cell proliferation by upregulating heme oxygenase-1 and p27KIP1. Arterioscler Thromb Vasc Biol. 2005; 25:1370-5.
  37. Li W, Tanaka K, Ihaya A, Fujibayashi Y, Takamatsu S, Morioka K, Sasaki M, Uesaka T, Kimura T, Yamada N, Tsuda T, Chiba Y. Gene therapy for chronic myocardial ischemia using platelet-derived endothelial cell growth factor in dogs. Am J Physiol Heart Circ Physiol. 2005; 288:H408-15.
  38. Tanaka K, Morioka K, Li W, Uesaka T, Sasaki M, Yamada N, Takamori A, Handa M, Tanabe S, and Ihaya A. Adventitial Inversion Technique without the Aid of Biologic Glue or Teflon Buttress for Acute Type A Aortic Dissection. Eur J Cardiothorac Surg, 2005; 28:864-70.
  39. Morioka K, Ikeda T, Tanabe S, Handa M, Takamori A, Yamada N, Li W, Uesaka T, Ihaya A, and Tanaka K. Surgical outcome of acute type A aortic dissection with brain damage. Cardioangiology. 2005; 57:99-100. (Manuscript in Japanese)
  40. Ihaya A, Tanaka K, Tanaka S, Tanabe S, Handa M, Takamori A, Yamada N, Tsuda T, Li W, Sasaki M, Uesaka T, Morioka K. Benefits and risks of warfarin therapy after axillofemoral bypass Surgical Therapy. 2005; 93:364-267. (Manuscript in Japanese)
  41. Ihaya A, Tsuda T, Kimura T, Morioka K, Uesaka T, Yamada N, Takamori A, Sasaki M, Li W, Tanaka K. Common femoral artery transection by blunt trauma. J Cardiovasc Surg (Torino). 2004; 45:590-1.
  42. Li W, Tanaka K, Chiba Y, Kimura T, Morioka K, Uesaka T, Ihaya A, Sasaki M, Tsuda T, Yamada N. Role of MMPs and plasminogen activators in angiogenesis after transmyocardial laser revascularization in dogs. Am J Physiol Heart Circ Physiol. 2003; 284:H23-30.
  43. Tanaka K, Ihaya A, Horiuci T, Morioka K, Kimura T, Uesaka T, Sasaki M, Uchinami M, Tsuda T, Yamada N, Li W, Hirai S, Tanabe S, Okubo Y, Tanaka S. Giant mediastinal bronchial artery aneurysm mimicking benign esophageal tumor: a case report and review of 26 cases from literature. J Vasc Surg. 2003; 38:1125-9.
  44. Li W (Corresponding author), Chiba Y, Kimura T, Morioka K, Uesaka T, Ihaya A, Muraoka R. Transmyocardial laser revascularization induced angiogenesis correlated with the expression of matrix metalloproteinases and platelet-derived endothelial cell growth factor. Eur J Cardiothorac Surg. 2001; 19:156-63.

Adam Belcher, PhD Candidate
Hong Yue, MD, PhD: Research Assistant Professor
Abu Hasanat Zulfiker, PhD
Lill Du, MD, PhD
Oliver Li