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Faculty

Ming Zhang

Ming Zhang, M.D., Ph.D.

Assistant Professor

Department of Anesthesiology, Department of Cell Biology

Tel: (718) 270-1413 •Fax: (718) 270-3928

e-mail: ming.zhang@downstate.edu

Innate Immunity and Ischemia / Reperfusion Injury

Recent advance in autoimmunity research reveals that innate immune system is able to recognize self-targets and initiate inflammatory response in a similar way as with pathogens. Studies of ischemia/reperfusion (I/R) models showed that reperfusion of ischemic tissues elicits an acute inflammatory response involving complement system which is activated by natural IgM. The recent identification of a monoclonal natural IgM that initiates I/R led to the identification of nonmuscle myosin heavy chain type II as the self-targets. New evidence further suggests that IgM binds initially to ischemic antigen providing a binding site for mannan binding lectin (MBL) which subsequently leads to activation of complement and results in tissue injury. Therefore, natural IgM mediated innate autoimmunity is likely responsible for the detrimental consequences in ischemic diseases. To target this early event of I/R pathogenesis, short peptides were screened from phage-displayed-peptide library and showed encouraging results to reduce I/R injury in animal models. This discovery of innate autoimmunity in I/R injury may provide a new avenue of therapy for ischemic diseases.

Our laboratory is devoted to the basic science research of I/R injury and have ongoing collaborations with scientists around the nation as well as internationally. Besides exploring the animal models of I/R injury, we team up with anesthesiologists, cardiac surgeons, cardiologists, and clinicians of various specialties to develop clinical research projects studying cardiovascular diseases.

Lab Members

  • Jolin Junying Liu, M.D., M.S. (Research Support Specialist)
  • Karen Wong (DMC Alumni Research Scholarship funded medical student 2013-14)
  • Fang-Chi Hsu (M.S. graduate student of NYU)
  • Sravani Rayala (M.S. graduate student of Long Island Univ.)
  • Andreas Tedjasukmana M.D.

Visit Dr. Zhang's Lab Team website »

Selected Publications

  1. Charlagorla P., Liu J., Patel M., Rushbrook J. I. and Zhang M. Loss of plasma membrane integrity, complement response and formation of reactive oxygen species during early myocardial ischemia/reperfusion. Mol Immunol, 2013; 56, 507-512. [Full Text]
  2. Zhang M, Hou Y, Cavusoglu E, Lee D, Steffensen R, Yang L, Bashari D, Villamil J, Moussa M, Fernaine G, Jensenius J, Marmur J, Ko W, Shevde K. MASP-2 Activation is Involved in Ischemia-related Necrotic Myocardial Injury in Humans. Int J Cardiol, (in press).
  3. Schwaeble WJ, Lynch NJ, Clark JE, Marber M, Samani NJ, Ali YM, Dudler T, Parent B, Lhotta K, Wallis R, Farrar CA, Sacks S, Lee H, Zhang M, Iwaki D, Takahashi M, Fujita T, Tedford CE, Stover CM. Targeting of mannan-binding lectin-associated serine protease-2 confers protection from myocardial and gastrointestinal ischemia/reperfusion injury. Proc Natl Acad Sci USA, 2011;108:7523-8. [Full Text]
  4. Lee H, Green DJ, Lai L, Hou YJ, Jensenius JC, Liu D, Cheong C, Park CG, Zhang M. Early complement factors in the local tissue immunocomplex generated during intestinal ischemia/reperfusion injury. Mol Immunol, 2010;47:972-1. [Full Text]
  5. Lai L, Lee D, Ko W, Shevde S, Zhang M. Deficiency of complement factor MBL in a patient required cardiac surgery after an acute myocardial infarction with underlining chronic lymphocytic leukemia. Int J Cardiol, 2010;139:e24-26. [Full Text]
  6. Hou YJ, Lee DC, Ko W, Kim A, Lee J, Shevde K, Zhang M. Perioperative mannan-binding lectin (MBL) patterns in cardiac surgery may correlate with the clinical outcomes in MBL deficient patients. Ann Thorac Surg, 2010;90:1357-8. [Full Text]
  7. Chiu IM, Phatnani H, Kuligowski M, Tapia JC, Carrasco MA, Zhang M, Maniatis T, Carroll MC. Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice. Proc Natl Acad Sci USA. 2009;106(49):20960-20965. [Full Text]
  8. Zhang M, Alicot EM, Carroll MC. Human natural IgM can induce ischemia/reperfusion injury in a murine intestinal model. Mol Immunol, 2008;45:4036-9. [Full Text]
  9. Zhang M, Takahashi K, Alicot EM, Vorup-Jensen T, Kessler B, Thiel S, Jensenius JC, Ezekowitz RA, Moore FD, Carroll MC. Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury. J Immunol, 2006;177:4727-34. [PubMed]
  10. Zhang M, Michael LH, Grosjean SA, Kelly RA, Carroll MC, Entman ML. The role of natural IgM in myocardial ischemia-reperfusion injury. J Mol Cell Cardiol, 2006;41:62-7. [PubMed]
  11. Zhang M, Alicot EM, Chiu I, Li J, Verna N, Vorup-Jensen T, Kessler B, Shimaoka M, Chan R, Friend D, Mahmood U, Weissleder R, Moore FD, Carroll MC. Identification of the target self-antigens in reperfusion injury. J Exp Med, 2006;203:141-52. [Full Text]
  12. Chan RK, Verna N, Afnan J, Zhang M, Ibrahim S, Carroll MC, Moore FD, Jr. Attenuation of skeletal muscle reperfusion injury with intravenous 12 amino acid peptides that bind to pathogenic IgM. Surgery, 2006;139:236-43. [PubMed]
  13. Zhang M, Austen WG, Jr., Chiu I, Alicot EM, Hung R, Ma M, Verna N, Xu M, Hechtman HB, Moore FD, Jr., Carroll MC. Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury. Proc Natl Acad Sci USA, 2004;101:3886-91. [Full Text]