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Research Interests

We are interested in understanding the mechanisms by which blood flow perfusion is regulated in the liver under the normal and stress conditions. Hepatic blood flow, particularly sinusoidal flow perfusion is essential for normal functions and metabolism of hepatocytes and also plays a crucial role in repair of injured cells in liver diseases. Regulation of sinusoidal blood perfusion consists of a delicate balance between the vasoconstrictor force and the vasodilator force that involve close interactions among the sinusoidal cells (i.e., endothelial cells, Kupffer cells, hepatic stellate cells) and hepatocytes. The primary interest of this laboratory is to delineate the relationship between the sinusoidal cells and hepatocytes with respect to their interaction contributing to the regulation of constrictor and dilator forces in various stress conditions such as endotoxemic shock, hemorrhagic shock, liver cirrhosis and liver transplant. We recently discovered, for example, that endothelin, a locally released vasoconstrictor by endothelial cells and perhaps more importantly by hepatocytes under certain diseases, induces sinusoidal constriction by contracting hepatic stellate cells thus reducing sinusoidal perfusion, and this effect is opposed by vasodilators nitric oxide and carbon monoxide. Our primary goal is to elucidate the mechanisms that regulate the balance of local constrictor and dilator forces in a variety of disease conditions and ultimately find drug interventions that help maintain liver perfusion under the stress conditions and rectify the injured tissue.

Ongoing Projects:

  1. Alterations in the regulatory mechanisms of hepatic microcirculatory perfusion in cirrhosis.
  2. Mechanisms of predisposition of the cirrhotic liver to hemorrhage/resuscitation and endotoxic shock.
  3. Mechanisms of hypercholesterolemia and hypertriglyceridemia induced liver injury in Apo-CI transgenic mice.
  4. Effect of caloric restriction on steatohepatitis in hyperlipidemic environment.

Areas of Interest:

  • Liver Microcirculation under Normal and Pathological Conditions
    • Physiologic Control and Regulation in Hepatic Blood Circulation
    • Regulation and Dysregulation of Hepatic Microcirculation in Cirrhosis
    • Regulation of Sinusoidal Perfusion in Shock and Postischemic Reperfusion
  • Liver Transplant
    • Hypothermic Machine Perfusion Preservation
    • Role of Kupffer Cells in Mediation of Microcirculatory Injury during Acute Rejection
    • Hyperacute Liver Rejection in Xenotransplant
  • Liver Regeneration
    • Liver Regeneration and Its Control Mechanisms Following Partial Hepatectomy
    • Role of Nonparenchymal Cells in Liver Regeneration

Courses Taught

  • BIOL 3273 Animal Physiology
  • BIOL 4600 Senior Seminar
  • BIOL 6273 Advanced Human Physiology (offered for graduate credit)
  • BIOL 6050 Phathophysiology (offered for graduate credit)
  • BIOL 6000 Graduate Special Topics: Cell Membranes (offered for graduate credit)
  • BIOL 6104/8104 Integrated Systems Physiology (offered for graduate credit)
  • MEGR 6109/8109 Biotechnology and Bioengineering (offered for graduate credit)

Professional Positions

  • Associate Professor, Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina, 2003 – Present
  • Assistant Professor, Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina, 1996 – 2003
  • Postdoctoral Fellow, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 1992 – 1996

Education

  • Postdoctoral Training, Johns Hopkins University School of Medicine (1992-1996).
  • Ph.D in Biomedical Science, Specialization in Physiology, 1992, University of South Carolina, Columbia, South Carolina.
  • M.A. in Sports Medicine, 1987, Springfield College, Springfield, Massachusetts.
  • B.S. in Sports Medicine, 1982, Chengdu College of Sports Medicine, Chengdu, China.

Selected Publications

  • Chun, K., J. Zhang, J. Biewer, D. Ferguson, and M. G. Clemens. Microcirculatory failure correlates with lethal hepatocyte injury in ischemic/reperfused rat livers. Shock. 1(1): 3-9, 1994.
  • Zhang, J. X., W. Pegoli, Jr., and M. G. Clemens. Endothelin-1 induces direct constriction of hepatic sinusoids. American Journal of Physiology. 266 (Gastrointest. Liver Physiol. 29): G624-G632, 1994.
  • Bauer, M., J. X. Zhang, I. Bauer, and M. G. Clemens. Endothelin-1 induced alterations of hepatic microvasculation: sinusoidal and extrasinusoidal sites of action. American Journal of Physiology. 267 (Gastrointest. Liver Physiol. 30): G143-G149, 1994.
  • Zhang, J. X., D. V. Jones, and M. G. Clemens. Effect of activation on neutrophil-induced hepatic microvascular injury in isolated rat liver. Shock. 1(4): 273-278,1994.
  • Zhang, J. X., M. Bauer, and M. G. Clemens. Vessel and target cell specific actions of endothelin-1 and endothelin-3 in rat liver. American Journal of Physiology. 269(Gastrointest. Liver Physiol. 32): G269-G277, 1995.
  • Bauer, M., J. X. Zhang, I. Bauer, and M. G. Clemens. Endothelin-1 as a regulator of hepatic microcirculation: sublobular distribution of effects and impact on hepatocellular secretory function. Shock. 1(6): 457-465, 1994.
  • Clemens, M. G., M. Bauer, C. Gingalewski, E. Miescher, and J. Zhang. Editorial review: hepatic intercellular communication in shock and inflammation. Shock. 2(1): 1-9, 1994.
  • Clemens, M. G., M. Bauer, C. Gingalewski, J. Zhang, and A. DeMaio. Heterogeneity of hepatocellular response: role of intercellular communication. In: Host defense dysfunction in trauma, shock and sepsis, edited by E. Faist, F. Schildberg, and A. Baue. Berlin: Springer Verlag, 1995.
  • Bauer, M., N. C. Paquette, J. X. Zhang, I. Bauer, B. H. J. Pannen, S. R. Kleeberger, and M. G. Clemens. Chronic ethanol consumption increases hepatic sinusoidal contractile response to endothelin-1. Hepatology. 22: 1565-1576,1995.
  • Pannen, B. H. J., Bauer, M., J. X. Zhang, I. L. Robotham, M. G. Clemens. Endotoxin pretreatment enhances the portal venous contractile response to endothelin-1. American Journal of Physiology. 270: H7-15, 1996.
  • Bauer, I., M. Bauer, B. H. J. Pannen, M. J. Leinwand, J. X. Zhang, and M. G. Clemens. Chronic ethanol consumption exacerbates liver injury following hemorrhagic shock: role of sinusoidal perfusion failure. Shock. 4(5): 1-8, 1995.
  • Pannen, B. H. J., M. Bauer, J. X. Zhang, I. L. Robotham, M. G. Clemens. A time-dependent balance between endothelin and nitric oxide regulates portal vascular resistance following endotoxin. American Journal of Physiology. 271: H1953-H1961.
  • Morita, Y., G. B. Bulkley, J. X. Zhang, and M. G. Clemens. Regulation of prolonged endothelin-1-induced arterial constriction in the rat mesenteric artery in vivo, American Journal of Physiology. In press.
  • Rai, R., J.X. Zhang, M. G. Clemens, and A. M. Diel. Gadolinium chloride alters acinar distribution of phagocytosis and balance between pro-and anti-inflammatory cytokines. Shock. (6:4): 243-7, 1996.
  • Bauer, M., B. H. J. Pannen, I. Bauer, C. Herzog, G. A. Wanner, R. Hanselmann, J. X. Zhang, M. G. Clemens and R. Larson. Evidence for a functional link between stress response and vascular control in hepatic portal circulation. American Journal of Physiology. 271: G929-G935, 1996.
  • Pannen BHJ., Bauer M, Noldge-Schomburg GFE, Zhang JX, Robotham JL, Clemens MG, Geiger KK. Regulation of hepatic blood flow during resuscitation from hemorrhagic shock: role of NO and endothelins. Am J Physiol. 272 (Heart Circ. Physiol. 41): H2736-H2745, 1997.
  • Clemens, M. G., B. H. J. Pannen, M. Bauer, J. X. Zhang. Remodeling of hepatic microvascular responsiveness following ischemia/reperfusion. Shock. (8:2): 80-5, 1997.
  • Garcia-Pagán, J.C., J. X. Zhang, N. Sonin, K. Nakanishi, M. G. Clemens. Ischemia/reperfusion induces an increase in the hepatic portal vasoconstrictive response to endothelin-1. Shock. 11: 325-329, 1999.
  • Sonin, N.V., J.C. Garcia-Pagán, K. Nakanishi, J. X. Zhang, M. G. Clemens. Patterns of vasoregulatory gene expression in the liver response to ischemia/reperfusion and endotoxemia. Shock. 11: 175-179, 1999.
  • Clemens, MG and JX Zhang. Regulation of sinusoidal perfusion: in vivo methodology and control by endothelins. Seminars in Liver Disease. 19(4): 383-396, 1999.
  • Baveja R, Zhang JX, and Clemens MG. In vivo assessment of endothelin-induced heterogeneity of hepatic tissue perfusion. Shock. (In Press)
  • Yokoyama, Y., R. Baveja, N. Sonin, K. Nakanishi, J.X. Zhang, and M.G. Clemens. Altered endothelin receptor subtype expression in hepatic injury after ischemia/reperfusion. Shock. 13(1): 72-8, 20
  • Bauer, M., I. Bauer, N. Sonin, N. Kresge, R. Baveja, D. Harding, Y. Yokoyama, J.X. Zhang, M.G. Clemens. Functional significance of endothelin-B receptor expression in endotoxemia. Hepatology. 31(4): 937-47, 2000.
  • Lee, C.Y., J.X. Zhang, H. DeSilva, R.N. Coger, M.G. Clemens. Heterogeneous flow patterns during hypothermic machine perfusion preservation of livers. Transplantation. 70(12): 1797-1802, 2000.
  • Yokoyama, Y., R. Baveja, N. Sonin, M.G. Clemens, and J.X. Zhang. Hepatic neovascularization following partial portal vein ligation: A novel mechanism of chronic regulation in hepatic blood flow. American Journal of Physiology. 280(1): G21-G31, 2001.
  • Yokoyama, Y., A. Wawrzyniak, R. Baveja, N. Sonin, M.G. Clemens, and J.X. Zhang. Altered endothelin receptors in prehepatic portal hypertension in the rat: predisposition of the hepatic microcirculatory dysfunction. Journal of Hepatology. 35: 29-36, 2001.
  • Baveja, R., J.X. Zhang, and M.G. Clemens. In vivo assessment of endothelin-induced heterogeneity of hepatic tissue perfusion. Shock. 15(3): 186-92, 2001.
  • Baveja R, Zhang JX, and Clemens MG. Endothelin-1 induces microheterogeneity of hepatic tissue PO2 in vivo. Shock. 15(3): 186-92, 2001.
  • Baveja R, Keller S, Yokoyama Y, Sonin N, Clemens MG, Zhang JX. LPS-induced imbalanced expression of hepatic vascular stress genes in cirrhosis: possible mechanism of increased susceptibility to endotoxemia. Shock. 17(4): 316-21, 2002.
  • Yukihiro Yokoyama, Rajiv Baveja, Nicole Kresge, Natalie Sonin, Kazuya Nakanishi Jian X. Zhang, Christopher A. Gitzelmann and Mark G. Clemens Endothelin receptor remodeling induces the portal venous hyper-response to endothelin-1 following endotoxin pretreatment. Shock. 17(1): 36-40, 2002.
  • Lee, C.Y., J.X. Zhang, Jon w. Jones, James H. Southard, M.G. Clemens. Functional recovery of preserved livers following warm ischemia: Improvement by machine perfusion preservation. Transplantation. 74(7): 944-51, 2002.
  • Yokoyama Y, Alterman DM, Sarmadi AH, Baveja R, Zhang JX, Huynh T, Clemens MG. Hepatic vascular response to elevated intraperitoneal pressure in the rat. J Surg Res. 105(2): 86-94, 2002.
  • Baveja R, Kresge N, Ashburn JH, Keller S, Yokoyama Y, Sonin N, Zhang JX, Huynh T, Clemens MG. Potentiated hepatic microcirculatory response to endothelin-1 during polymicrobial sepsis. Shock. 18(5): 415-22, 2002.
  • Baveja R, Yokoyama Y, Korneszczuk K, Zhang JX, Clemens MG. Endothelin 1 impairs oxygen delivery in livers from LPS-primed animals. Shock. 17(5): 383-8, 2002.
  • Rensing H, Bauer I, Zhang JX, Paxian M, Pannen BH, Yokoyama Y, Clemens MG, Bauer M. Endothelin-1 and heme oxygenase-1 as modulators of sinusoidal tone in the stress-exposed rat liver. Hepatology. 36(6): 1453-65, 2002.
  • Yokoyama Y, Xu H, Kresge N, Keller S, Sarmadi AH, Baveja R, Clemens MG, Zhang JX. Role of thromboxane A2 in early BDL-induced portal hypertension. American Journal of Physiology. 284(3): G453-60, 2003.
  • Lee CY, Jain S, Duncan HM, Zhang JX, Jones JW Jr, Southard JH, Clemens MG. Survival transplantation of preserved non-heart-beating donor rat livers: preservation by hypothermic machine perfusion. Transplantation. 76(10): 1432-6, 2003.
  • Xu, H, Lee CY, Clemens MG, Zhang JX. Prolonged hypothermic machine perfusion preserves hepatocellular function but potentiates endothelial cell dysfunction in rat livers. Transplantation. 77(11):1676-82. 2004.
  • Jain S, Xu H, Duncan H, Jones JW Jr, Zhang JX, Clemens MG, Lee CY. Ex-vivo study of flow dynamics and endothelial cell structure during extended hypothermic machine perfusion preservation of livers. Cryobiology. 48(3):322-32. 2004.
  • Ashburn JH, Baveja R, Kresge N, Korneszczuk K, Keller S, Karaa A, Yokoyama Y, Zhang JX, Huynh T, Clemens MG. Remote trauma sensitizes hepatic microcirculation to endothelin via caveolin inhibition of eNOS activity. Shock. 22(2):120-30. 2004.
  • Xu H, Korneszczuk K, Karaa A, Lin T, Clemens MG, Zhang JX. Thromboxane A2 from Kupffer cells contributes to the hyperresponsiveness of hepatic portal circulation to endothelin-1 in endotoxemic rats. Am J Physiol Gastrointest Liver Physiol. 288(2):G277-83. 2005.
  • Xu H, Zhang JX, Jones JW, Southard JH, Clemens MG, Lee CY. Hypothermic machine perfusion of rat livers preserves endothelial cell function. Transplant Proc. Jan-Feb;37(1):335-7. 2005.
  • Keller S, Karaa A, Paxian M, Clemens MG, Zhang JX. Inhibition of endothelin-1-mediated up-regulation of iNOS by bosentan ameliorates endotoxin-induced liver injury in cirrhosis. Shock. Mar;25(3):306-13. 2006.
  • Yokoyama Y, Wawrzyniak A, Sarmadi AM, Baveja R, Gruber HE, Clemens MG, Zhang JX. Hepatic Arterial Flow Becomes the Primary Supply of Sinusoids Following Partial Portal Vein Ligation in Rats. J Gastroenterol Hepatol. Oct;21(10):1567-74, 2006.
  • Karaa A, Kamoun WS, Xu H, Zhang J, Clemens MG. Differential effects of oxidative stress on hepatic endothelial and Kupffer cell eicosanoid release in response to endothelin-1. Microcirculation. Sep;13(6):457-66, 2006.
  • Miller AM, Masrorpour M, Klaus C, and Zhang JX. LPS Exacerbates Endothelin-1 Induced Activation of Cytosolic Phosoholipase A2 and Thromboxane A2 Production from Kupffer Cells of the Prefibrotic Rat Liver. Journal of Hepatology. Feb;46(2):276-85. 2007.

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