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PERSONNEL
Profiles
Name
Li-Ming Zhang, MD
Title
Associate Professor
Office Address
200 Lothrop Street
MUH Anesthesia, Suite 467.2
Pittsburgh, PA 15213
Phone
412-648-6077
FAX
412-648-6014
Undergraduate School
Xiangya Medical University, Changsha, Hunan, China
Medical/Graduate School
Xiangya Medical University, Changsha, Hunan, China, MD
Residency
Brigham & Women's Hospital, Harvard Medical School
University of Pittsburgh Medical Center
Fellowship
Radcliffe Infirmary, Oxford University, UK. Clinical Pharmacology
Medical University of South Carolina, Clinical Pharmacology
Subspecialty Research Interests
Functional genomics of ventilator-induced lung injury;
Signaling of S-nitroso-albumin in pulmonary endothelium; and
Simulation teaching and research and international collaboration
Profile

Dr. Zhang’s current research focuses on identifying the susceptibility genes of ventilator-induced lung injury via an unbiased genome-wide association study (GWAS) in inbred mice and to evaluate its relevant functional significance. Mechanical ventilation (MV) is a valued palliative therapy for the management of a variety of critically ill patients. Nonetheless, this therapy may produce an iatrogenic condition referred to as ventilator-induced lung injury (VILI). Sensitivity to VILI varies greatly in patient subpopulations, suggesting that genetic determinants may control individual susceptibility. Although much effort and progress has been made over past 40 years, the underlying mechanisms behind MV and its cellular responses that result in VILI remain unclear.  MV is an important risk factor in the pathogenesis of ALI. High tidal volume VILI animal models have exhibited increased alveolar-capillary permeability, inflammation leading to pulmonary edema, and diffuse alveolar damage that closely mimics the pathologic aspects of ALI; therefore, the VILI animal model is a realistic tool to explore the underlying mechanisms for ALI. Using an unbiased GWAS of a genetically diverse panel of 23 mouse strains, we recently identified a stretch inducible molecule and a Wnt/β-catenin signaling pathway target gene, WNT1 inducible signaling pathway protein 1 (WISP1) in a murine model of VILI. We found that WISP1 protein level increased in the lung and bronchoalveolar lavage fluid after VILI and that anti-WISP1 antibody decreased lung injury, whereas intratracheal administration of recombinant WISP1 protein increased lung permeability in VILI. Moreover, we have discovered that the innate immune signaling via TLR4 plays a critical role in the pathogenesis of VILI and that the stretch-induced WISP1 expression and its pro-inflammatory effects are TLR4-dependent. Successful completion of this study could yield novel insights that could lead to a diagnostic (e.g. biomarker) and/or therapeutic target for future translation in humans.

Selected Publications
  • Li HH, Li Q, Liu P, Liu Y, Li J, Wasserloos K, Chao W, You M, Oury TD, Chhinder S, Hackam DJ, Billiar TR, Leikauf GD, Pitt BR, Zhang LM. WNT1 Inducible Signaling Pathway Protein 1 (WISP1) Contributes to Ventilator-Induced Lung Injury. Am J Respir Cell Mol Biol. 2012 Oct; 47(4):528-35. PMID:22700866
  • Li HH, Xu J, Wasserloos KJ, Li J, Tyurina YY, Kagan VE, Wang XR, Chen AF, Liu ZQ, Stoyanovsky D, Pitt BR and Zhang LM. Cytoprotective effects of Albumin, Nitrosated or Reduced, in Cultured Rat Pulmonary Vascular Cells. Am J. Physiol Lung Cell Mol Physiol: 2011 Apr, 300(4), L526 – 33. Epub 2011. PMID:21239532
  • Li HH, Su XL, Yan XB, Wasserloos KJ, Chao W, Kaynar AM, Liu ZQ, Leikauf GD, Pitt BR and Zhang LM. Toll-like Receptor 4-Myeloid Differentiation Factor 88 Signaling Contributes to Ventilator-induced Lung Injury in Mice. Anesthesiology, 113(3):619-629. (2010)
  • Zhang LM, St. Croix CM, Cao R, Wasserloos K, Watkins SC, Stevens T, Li S, Tyurin V, Kagan VE and Pitt BR. Cell-surface protein disulfide isomerase is required for transnitrosation of metallothionein by S-nitroso-albumin in intact rat pulmonary vascular endothelial cells. Exp. Biol. Med. 231:1507-1515. (2006)
  • Zhang, LM, Castresana MR, Shaker IJ, Dalton ML, Leeper-Woodford SK and Newman WH. Increased intracellular cyclic adenosine 3’5’-monophosphate inhibits release of turmor necrosis factor alpha from human vascular tissue and cultured smooth muscle cells. Crit. Care Med 25:1855-1861. (1997)
  • Zhang, LM, Castresana MR, McDonald, MH Johnson JH, and Newman WH. Response of human artery, vein, and cultured smooth muscle cells to atrial and C-type natriuretic peptide. Crit. Care Med. 24: 306-310. (1996)