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Dr. Mark G. Clemens

   

Professor and Vice Chair, Dept. of Biology

Office: (704) 687-8682

Lab: (704) 687-8675

Woodward 486A

 

General Information

Research Interests

  • Regulation of liver microcirculation: Role of stress-inducible vasoactive mediators (endothelin, nitric oxide synthase, heme oxygenase) in altering vascular responsiveness in the liver following oxidative or inflammatory stress. Mechanisms of control of sinusoid perfusion by hepatic stellate cells, especially related to components of phenotypic transformation in response to injury.
  • Hepatic metabolic response to infection. Mechanisms of altered carbohydrate metabolism during sepsis, especially related to differentiation between inflammation-induced changes in gene expression and perfusion supply/demand ratio as mediators of decreased gluconeogenesis.
  • Application of imaging techniques to biological research. In vivo video microscopy for study of liver microcirculation; application of quantitative fluorescence techniques to monitoring of cellular processes in intact organs or in vivo.
  • Engineered liver support systems:  Bioengineering Research Partnership  BRP page

Professional Experience

  • Research Scientist, Department of Surgery,Yale University, 1981-86
  • Assistant Professor, Departments of Surgery and Physiology, Johns Hopkins School of Medicine, 1986-91
  • Associate Professor, Departments of Surgery and Physiology, Johns Hopkins School of Medicine, 1992-96
  • Robert Garrett Scholar, Johns Hopkins School of Medicine, 1986-96
  • Director of Pediatric Surgery Research, Johns Hopkins School of Medicine, 1986-96

Education

  • B.S., Physical Therapy; St. Louis University, 1975
  • Ph.D., Physiology; St. Louis University, 1979
  • Postdoctoral Fellowship, Physiology and Metabolism; Yale University, 1980-81

Courses Taught (*offered for Graduate Credit)

Selected Recent Publications

  1. Mark G. CLEMENS, Walid KAMOUN, Amel KARAA, and Sandra MERKEL.  Altered caveolae-associated signalling in liver sinusoidal endothelial cells following inflammation.  Microcirculation Annual 21: 7-10, 2005

  2.  Karaa A, Kamoun WS, Clemens MG.  Chronic Ethanol Sensitizes the Liver to Endotoxin via Effects on Endothelial Nitric Oxide Synthase Regulation.  Shock  24(5):447-54, 2005

  3. Kamoun WS, Karaa A, Kresge N, M. Merkel S, Korneszczuk K, Clemens MG.  LPS Inhibits Endothelin-1 Induced Endothelial Nitric Oxide Synthase Activation through a Negative Feedback Involving Caveolin-1.  Hepatology  Jan;43(1):182-90, 2006

  4. Keller S, Karaa A, Paxian M, Clemens MG., and Zhang J.  Inhibition of Endothelin-1 Mediated Upregulation of iNOS by Bosentan Ameliorates Endotoxin-Induced Liver Injury in Cirrhosis.  Shock. Mar;25(3):306-13, 2006

  5. Clemens MG.  What's new in shock, October 2005?Shock. 24(4):297-9, 2005

  6. Zinchenko YS, Schrum LW, Clemens M, Coger RN. Hepatocyte and kupffer cells co-cultured on micropatterned surfaces to optimize hepatocyte function.Tissue Eng. 2006 Apr;12(4):751-61

  7. 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. 2006 Sep;13(6):457-66.

  8. Dreau D, Karaa A, Culberson C, Wyan H, McKillop IH, Clemens MG. Bosentan((R)) inhibits tumor vascularization and bone metastasis in an immunocompetent skin-fold chamber model of breast carcinoma cell metastasis.  Clin Exp Metastasis. 2006 Jul 7;

  9. Lee SH, Coger RN and Clemens MG.  Antioxidant functionality in hepatocytes using enhanced collagen extracellular matrix under different oxygen tensions.  Tissue Engineering 2006 (in press)

  10. Karaa A, Kamoun W and Clemens MG.  Oxidative stress disrupts nitric oxide synthase activation in liver endothelial cells.  Free Radical Biology and Medicine (In Press)

  11. Kamoun WS, Shin MC., Keller S, Karaa A, Huynh T, Clemens MG.  Induction of Biphasic Changes in Perfusion Heterogeneity of Rat Liver Following Sequential Stress in Vivo.  Shock (In Press)

  12. Mark G. CLEMENS, Walid KAMOUN, Amel KARAA, and Sandra MERKEL.  Altered caveolae-associated signalling in liver sinusoidal endothelial cells following inflammation.  Microcirculation Annual 2005 (In Press)

  13. Zinchenko YS., Schrum LW., Clemens M, and  Coger RN.  Hepatocyte  and Kupffer Cells Co-cultured on Micropatterned Surfaces to Optimize Hepatocyte Function.  Tissue Engineering (In Press)

  14. Merkel SM,  Kamoun W,  Karaa A,  Korneszczuk K, . Schrum LW and Mark G. Clemens.  LPS Inhibits Endothelin-1-Mediated eNOS Translocation to the Cell Membrane in Sinusoidal Endothelial Cells.  Microcirculation 12: 433-442, 2005.

  15. Keller SA,  Paxian M, Ashburn JH , Clemens MG, and Toan Huynh.  Kupffer Cell Ablation Improves Hepatic Microcirculation after Trauma and Sepsis.  J. Trauma 58(4):740-9 2005.

  16. Keller SA,  Paxian M, Lee SM,Clemens MG, and Toan Huynh.  Kupffer Cell Ablation Attenuates Cyclooxygenase-2 Expression after Trauma and Sepsis.  J Surg Res 124(1): 126-33, 2005.

  17. Kamoun WS, Shin MC, Karaa A, Clemens MG.  Quantification of hepatic microcirculation heterogeneity of perfusion: Effects of endothelin-1.  Microvasc Res. 2005 May;69(3):180-6.

  18. Xu H,  Korneszczuk K, Karaa A ,  Lin T, Clemens MG, and Jian X. Zhang 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: G277-G283, 2005

  19. Jain S, Lee CY, Baicu S, Duncan H, Xu H, Jones JW Jr, Clemens MG, Brassil J, Taylor MJ, Brockbank KG.  Hepatic function in hypothermically stored porcine livers: comparison of hypothermic machine perfusion vs cold storage. Transplant Proc. 37(1):340-1, 2005.

  20. Xu H, Zhang JX, Jones JW, Southard JH, Clemens MG, Lee CY.  Hypothermic machine perfusion of rat livers preserves endothelial cell function.  Transplant Proc.37(1):335-7, 2005.

  21. 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. 2004 Jun;48(3):322-32

  22. Markus Paxian, Steve A. Keller, Rajiv Baveja, Katarzyna Korneszczuk, Toan T. Huynh, and Mark G. Clemens.   Functional link between ETB receptors and eNOS maintain tissue oxygenation in the normal liver.  Microcirulation 11(5):435-49, 2004

  23. Markus Paxian, Steve A. Keller, Toan T. Huynh, and Mark G. Clemens  Perflubron emulsion improves hepatic microvascular integrity and mitochondrial redox state following hemorrhagic shock.  Shock 20(5): 449-57, 2003 .

  24. Paxian M,. Keller  S, Cross B, Huynh T, and Mark G. Clemens.  High resolution visualization of oxygen distribution in the liver in vivo.  American Journal of Physiology 286(1): G37-44, 2004.

  25. Xu H, Lee CY, Clemens MG, Zhang JX.  Prolonged Hypothermic Machine Perfusion Preserves Hepatocellular Function but Potentiates Endothelial Cell Dysfunction in Rat Livers. Transplantation (in Press)

  26. 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. 2003 Nov 27; 76(10): 1432-6.

  27. 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.  Am J Physiol Gastrointest Liver Physiol 2003 Mar;284(3):G453-60

  28. 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 2002 Dec;36(6):1453-65

  29. Ashburn J H,.   Rajiv Baveja, Nicole Kresge, Katarzyna Korneszczuk, Steve Keller, Amel Karaa, Yukihiro Yokoyama,  Jian X. Zhang, Toan Huynh, and Mark G. Clemens.  Remote trauma sensitizes hepatic microcirculation to endothelin via caveolin inhibition of eNOS activity.  Shock (in press) 

  30. Yokoyama Y, Alterman D, Sarmadi A, Baveja R, Zhang J, Huynh T and Clemens MG.  Hepatic Vascular response to elevated intraperitoneal pressure in the rat.  J. Surg Res 2002 Jun 15;105(2):86-94

  31.  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 2002 Nov;18(5):415-22

  32.  Baveja R, Yokoyama Y, Korneszczuk K, Zhang JX, Clemens MG.  Endothelin 1 impairs oxygen delivery in livers from LPS-primed animals. Shock 2002 May;17(5):383-8

  33. Lee CY, Zhang JX, Jones JW Jr, Southard JH, Clemens MG.  Functional recovery of preserved livers following warm ischemia: improvement by machine perfusion preservation.  Transplantation 2002 Oct 15;74(7):944-51

  34. 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 2002 Apr;17(4):316-21

  35.  McConnell NA, Yunus RS, Gross SA, Bost KL, Clemens MG, Hughes FM Jr.   Water permeability of an ovarian antral follicle is predominantly transcellular and mediated by aquaporins.  Endocrinology 2002 Aug;143(8):2905-12

  36. 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 2002 Jan;17(1):36-40

  37. 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. 2001 Jul;35(1):29-36

  38.  Baveja R, Zhang JX, Clemens MG.  In vivo assessment of endothelin-induced heterogeneity of hepatic tissue perfusion. Shock 2001 Mar;15(3):186-92

  39.  Yokoyama Y, Baveja R, Sonin N, Clemens MG, Zhang JX. Hepatic neovascularization after partial portal vein ligation: novel mechanism of chronic regulation of blood flow.Am J Physiol Gastrointest Liver Physiol. 280(1): G21-G31, 2001

  40. DeMaio A, Gingalewski C, Theodorakis N, Clemens MG.  Interruption of hepatic gap junctional communication in the rat during inflammation induced by bacterial lipopolysaccharide.  Shock 14(1):53-9, 2000.

  41. Lee S-M, M-J Park, T-S Cho and MG Clemens.  Hepatic injury and lipid peroxidation during ischemia and reperfusion.  Shock 2000;13(4):279-84

  42. Yokoyama Y, Baveja R, Sonin N, Nakanishi, Zhang JX, and Clemens MG. The role of endothelin receptor remodeling in microvascular response after ischemia / reperfusion.  Shock 13(1):72-8, 2000.
  43. St. John J, Barbee W, Sonin N, Clemens MG, Watts JA.  Inhibition of poly (ADP-ribose) synthetase improves vascular contractile responses following trauma-hemorrhage and resuscitation. Shock 12: 188-195, 1999.

  44. Bauer M, Bauer I, Sonin NV, Kresge N, Baveja R, Yokoyama Y, Harding D, Zhang JX, Clemens MG. Functional significance of endothelin B receptors in mediating sinusoidal and extrasinusoidal effects of endothelins in the intact rat liver.Hepatology 31(4):937-47, 2000

  45. Yutaka Morita, Toshikazu Yoshikawa, Satoshi Takeda, Norimasa Yoshida, Mark G. Clemens and Motoharu Kondo. Role of lipid peroxidation in free fatty acid-induced isolated rat pancreatic acinar cell injury. Pancreas 17: 383- 389, 1998

  46. Sonin NV, Garcia-Pagan JC, Nakanishi K, Zhang JX, Clemens MG. Patterns of vasoregulatory gene expression in the liver response to ischemia / reperfusion and endotoxemia. Shock11: 175-179, 1999.

  47. Clemens, MG. Nitric Oxide in liver injury. Hepatology 30: 1-5, 1999

  48. Clemens MG. Liver circulation in portal hypertension. Hepato-Gastroenterology 46 (Supplement II): 1429-1433, 1999.

  49. Garcia-Pagán J-C, Zhang JX, Sonin N, Nakanishi K, Clemens Mark G. Ischemia / reperfusion induces an increase in the hepatic portal vasoconstrictive response to endothelin-1. Shock 11: 325-329, 1999

  50. Susumu Kobayashi, Elizabeth Miescher, and Mark G. Clemens A synergistic effect of extracellular hypocalcemia for hyperoxic reoxygenation injury in rat hepatocytes. Transplantation 67: 451-457, 1999

  51. Clemens, MG and JX Zhang. Regulation of sinusoidal perfusion: in vivo methodology and control by endothelins. Seminars in Liver Disease 19(4):383-96, 1999

  52. Pannen BHJ, Geiger KK, Clemens MG, Bauer M, Al-Adili F. Role of endothelins and nitric oxide in hepatic reperfusion injury in the rat. Hepatology 27:755-64, 1998.

  53. Clemens, MG. Does altered regulation of ecNOS in sinusoidal endothelial cells determine increased intrahepatic resistance leading to portal hypertension? Hepatology 27:1745-1747, 1998.

  54. Pannen BHJ, Kohler N, Hole B, Bauer M, Clemens MG, Geiger KK. Protective Role of Endogenous Carbon Monoxide in Hepatic Microcirculatory Dysfunction after Hemorrhagic Shock in Rats J. Clin Invest. 102: 1220-1228, 1998.

  55. Yang SQ; Lin HZ; Lane MD; Clemens M; Diehl AM. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci U S A 1997 Mar 18;94(6):2557-62

  56. Clemens MG, Bauer M, Pannen BHJ, Bauer I, and JX Zhang, Remodeling of hepatic microvascular responsiveness after ischemia/reperfusion. Shock 8: 80-85, 1997
  57. Bauer I, Wanner G, Rensing H, Alte C, Miescher E, Wolf B, Pannen BHJ, Clemens MG, and Bauer M. Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress exposed rat liver. Hepatology 27: 829-838, 1998.
  58. Pannen PHJ, M Bauer, E Noldge-Schomburg, JX Zhang, JL Robotham, MG Clemens , and KK Geiger. Regulation of hepatic blood flw during resuscitation from hemorrhagic shock: Role of nitric oxide and endothelins. Am J Physiol Jun;272(6 Pt 2):H2736-45, 1997.
  59. Bauer M, BHJ Pannen, I Bauer, C Herzog, GA Wanner, R Hanselmann, JX Zhang, MG Clemens and R Larsen. In vivo evidence for a functional link between stress response and vascular control in hepatic portal circulation. Am. J. Physiol. 271: G929-G935, 1996
  60. Rai R, JX Zhang, MG Clemens and AM Diehl. Gadolinium chloride alters acinar distribution of phagocytosis and balance between pro- and anti-inflammatory cytokines. Shock 6(4):243-7, 1996}
  61. Pannen BHJ, Bauer M, Zhang JX, Robotham J and Clemens MG . A time-dependent balance between endothelin and nitric oxide regulates portal vascular resistance following endotoxin. Am. J. Physiol . 271: H1953-H1961, 1996.
  62. Jaeschke H, Smith CW,Clemens MG, Ganey PE and Roth RA. Mechanisms of inflammatory liver injury: Adhesion molecules and cytotoxicity of neutrophils. Toxicol Appl Pharmacol 139(2):213-26, 1996
  63. Gingalewski C, Wang K, Clemens MG, and DeMaio A. Posttranscriptional regulation of the connexin 32 gene in liver during acute inflammation. J. Cell Pysiol .166:461-467, 1996.
  64. Bauer I, Bauer M, Pannen BHJ, Leinwand MJ, Zhang JX and Clemens MG . Chronic ethanol consumption exacerbates liver injury following hemorrhagic shock: Role of sinusoidal perfusion failure. Shock4:324-331, 1995.
  65. Bauer M, Paquette NC, Zhang JX, Bauer I, Pannen BHJ, Kleeburger SR and  Clemens MG. Chronic ethanol consumtion increases hepatic sinusoidal contractile response to endothelin-1. Hepatology 22: 1565-1576, 1995.
  66. Pannen BHJ, Bauer M, Zhang JX, Robotham JL, Clemens MG . Endotoxin pretreatment enhances the portal venous contractile response to endothelin-1. Am. J. Physiol. 270:H7-15, 1996
  67. Zhang J, Bauer M, Clemens MG . Vessel and target cell specific actions of endothelin-1 and endothelin-3 in rat liver. Am J Physiol 269:G269-G277, 1995
  68. Deutschman CS, DeMaio A, Clemens MG. Sepsis-induced attenuation of glucagon and 8-bromo-cyclic AMP modulation of phosphoenolpyruvate carboxykinase gene expression. Am J Physiol 269:R584-R591, 1995.
  69. Wang K, Deutschman CS, Clemens MG, DeMaio A. Reciprocal expression of phosphoenolpyruvate carboxykinase (PEPCK) and acute phase genes during acute inflammation. Shock 3:204-209, 1995
  70. Bauer M, Zhang J, Bauer I, Clemens MG. Endothelin-1 induced alteration of hepatic microcirculation: sinusoidal and presinusoidal sites of action. Am J Physiol 267:G143-G149, 1994.
  71. Paidas CN, Clemens MG. Hormone effects on hepatic substrate preference in sepsis. Shock 1:94-100, 1994.
  72. Zhang JX, Pegoli W, Clemens MG. Endothelin-1 induces direct constriction of hepatic sinusoids. Am J Physiol 266:G624-G632, 1994.
 

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