Lisheng Zhang, MD

Assistant Professor in Medicine
Campus mail 447 Clin Res Lab Bldg, Durham, NC 27710
Phone (919) 684-6826
Email address lisheng.zhang@receptor-biol.duke.edu

My research efforts involves studying the pathogenesis of vein graft neointimal hyperplasia and atherosclerosis.
The greatest amount of my time in the past years has been devoted to developing and characterizing our interposition vein graft model in mice. This model allows us to use IVC to carotid artery transplants between congenic mice. These transplants allow us to ask the questions about which gene products contribute to the pathogenesis of vein graft disease. In addition, I have used carotid artery to carotid artery transplants to study the role of TNF receptors in atherosclerosis. For these studies, we have used apolipoprotein E-deficient mice as graft recipients.
By using mouse vein graft model we demonstrate that most of the neointimal cells in vein grafts originate from cellular pools outside of the vein graft at the time of its implantation. The importance of this work relates to our persistent inability to treat vein graft disease in human beings. The second work demonstrates that expression of the tumor necrosis factor receptor-1, even in just in the vein graft cells themselves, contributes to the pathogenesis of vein graft neointimal hyperplasia. In this project, I surgically created chimeric mice to demonstrate molecular mechanisms by which the tumor necrosis factor receptor-1 aggravates neointimal hyperplasia, a process that is believed to lay the foundation for accelerated atherosclerosis in vein grafts.
I have also adapted my vein graft procedure in mice to ask questions about the arterial wall’s role in atherosclerosis. This atherosclerosis model involves making carotid interposition grafts not with veins, but with the carotid artery of congenic mice, and placing them into the carotid artery of spontaneously atherogenic mice that are deficient in apolipoprotein E.
I plan to continue our studies related to the role of inflammatory cytokine receptors in neointimal hyperplasia and atherosclerosis. In addition, I envision extending this work with the surgical models I have created in mice.

Education and Training

  • M.D., Nanjing Medical University (China), 1988

Publications

Zhang, L, Wu, J-H, Otto, JC, Gurley, SB, Hauser, ER, Shenoy, SK, Nagi, K, Brian, L, Wertman, V, Mattocks, N, Lawson, JH, and Freedman, NJ. "Interleukin-9 mediates chronic kidney disease-dependent vein graft disease: a role for mast cells." Cardiovascular research 113, no. 13 (November 2017): 1551-1559.

PMID
29048463
Full Text

Stiber, JA, Wu, J-H, Zhang, L, Nepliouev, I, Zhang, Z-S, Bryson, VG, Brian, L, Bentley, RC, Gordon-Weeks, PR, Rosenberg, PB, and Freedman, NJ. "The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia." Arteriosclerosis, thrombosis, and vascular biology 36, no. 5 (May 2016): 984-993.

PMID
27013612
Full Text

Jean-Charles, P-Y, Zhang, L, Wu, J-H, Han, S-O, Brian, L, Freedman, NJ, and Shenoy, SK. "Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of β-Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor κB (NFκB) Activation." The Journal of biological chemistry 291, no. 14 (April 2016): 7450-7464.

PMID
26839314
Full Text

Jean-Charles, P-Y, Zhang, L, Han, S-O, Kommaddi, R, Wu, J-H, Freedman, N, and Shenoy, S. "A novel anti-inflammatory signaling role for the deubiquitinase USP20 in vivo." FASEB JOURNAL 28, no. 1 (April 2014).

Scholars@Duke

Black-Maier, EW, Wu, J-H, Fanaroff, AC, Akella, P, Zhang, L, Brian, L, Stiber, JA, Peppel, K, Eipper, BA, Mains, R, and Freedman, NJ. "The Dual RhoGEF Kalirin Reduces Atherosclerosis Through Endothelial Cell-Specific Mechanisms." November 26, 2013.

Scholars@Duke

Wu, J-H, Fanaroff, AC, Sharma, KC, Smith, LS, Brian, L, Eipper, BA, Mains, RE, Freedman, NJ, and Zhang, L. "Kalirin promotes neointimal hyperplasia by activating Rac in smooth muscle cells." Arterioscler Thromb Vasc Biol 33, no. 4 (April 2013): 702-708.

PMID
23288169
Full Text

Wu, J-H, Fanaroff, AC, Sharma, KC, Smith, LS, Brian, L, Eipper, BA, Mains, RE, Freedman, NJ, and Zhang, L. "Kalirin promotes neointimal hyperplasia by activating rac in smooth muscle cells." Arteriosclerosis, Thrombosis, and Vascular Biology 33, no. 4 (2013): 702-708.

Full Text

Lu, Y, Zhang, L, Liao, X, Sangwung, P, Prosdocimo, DA, Zhou, G, Votruba, AR, Brian, L, Han, YJ, Gao, H, Wang, Y, Shimizu, K, Weinert-Stein, K, Khrestian, M, Simon, DI, Freedman, NJ, and Jain, MK. "Kruppel-like factor 15 is critical for vascular infammation." Journal of Clinical Investigation 123, no. 10 (2013): 4232-4241.

PMID
23999430
Full Text

Zhang, L, Brian, L, and Freedman, NJ. "Vein graft neointimal hyperplasia is exacerbated by CXCR4 signaling in vein graft-extrinsic cells." J Vasc Surg 56, no. 5 (November 2012): 1390-1397.

PMID
22796120
Full Text

Wu, J-H, Zhang, L, Fanaroff, AC, Cai, X, Sharma, KC, Brian, L, Exum, ST, Shenoy, SK, Peppel, K, and Freedman, NJ. "G protein-coupled receptor kinase-5 attenuates atherosclerosis by regulating receptor tyrosine kinases and 7-transmembrane receptors." Arterioscler Thromb Vasc Biol 32, no. 2 (February 2012): 308-316.

PMID
22095977
Full Text

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