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

  • Resident, Xinjiang Medicine University (China), 1988 - 1994
  • M.D., Nanjing Medical University (China), 1988

Publications

Zhang, L, Wu, J-H, Huang, T-Q, Nepliouev, I, Brian, L, Zhang, Z, Wertman, V, Rudemiller, NP, McMahon, TJ, Shenoy, SK, Miller, FJ, Crowley, SD, Freedman, NJ, and Stiber, JA. "Drebrin regulates angiotensin II-induced aortic remodelling." Cardiovascular Research 114, no. 13 (November 2018): 1806-1815.

PMID
29931051
Full Text

Jean-Charles, P-Y, Wu, J-H, Zhang, L, Kaur, S, Nepliouev, I, Stiber, JA, Brian, L, Qi, R, Wertman, V, Shenoy, SK, and Freedman, NJ. "USP20 (Ubiquitin-Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis." Arteriosclerosis, Thrombosis, and Vascular Biology 38, no. 10 (October 2018): 2295-2305.

PMID
30354204
Full Text

Zhang, L, Wu, J-H, Huang, T-Q, Nepliouev, I, Brian, L, Zhang, Z, Rudemiller, NP, Crowley, SD, Freedman, NJ, and Stiber, JA. "Angiotensin II-Induced Aortic Inflammation and Remodeling Are Mitigated by the Actin-Binding Protein Drebrin." Scientific Sessions of the American-Heart-Association / Resuscitation Science Symposium. Anaheim, CA. November 11, 2017 - November 15, 2017.: LIPPINCOTT WILLIAMS & WILKINS, November 14, 2017.

Scholars@Duke

Wu, J, Davidson, AK, Fanaroff, AC, Zhang, L, Peppel, K, Brian, L, Eipper, BA, Mains, RE, and Freedman, NJ. "The Atherosclerosis Candidate Gene Product Kalirin Reduces Atherosclerosis via Macrophage-Specific Mechanisms." Scientific Sessions of the American-Heart-Association / Resuscitation Science Symposium. Anaheim, CA. November 11, 2017 - November 15, 2017.: LIPPINCOTT WILLIAMS & WILKINS, November 14, 2017.

Scholars@Duke

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

Wu, J-H, Zhang, L, Jean-Charles, P-Y, Davidson, AK, Brian, L, Qi, R, Shenoy, SK, and Freedman, NJ. "Ubiquitin-Specific Protease 20 Attenuates Atherosclerosis through Activity in Smooth Muscle Cells." November 11, 2016.

Scholars@Duke

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

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