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Limin Liu, Ph.D.

Limin Liu Associate Professor
Department of Microbiology and Immunology

University of California San Francisco
505 Parnassus Ave.
HSE 201 J, Box 0414
San Francisco, CA  94143-0414

Tel: (415)-476-1466
Fax: (415) 476-8201

Email: limin.liu@ucsf.edu

Websites:
Biomedical Sciences Graduate Program

Dr. Limin Liu is an Associate Professor in the Department of Microbiology & Immunology. He obtained his B.S. in Biology from University of Science and Technology of China and his Ph.D. in Molecular Biology from University of Missouri. He did postdoctoral research on the biology of nitric oxide (NO) at Duke University Medical Center.

Dr. Liu’s laboratory focuses on enzymatic deactivation of NO bioactivity and its role in asthma and other diseases. NO plays important roles in virtually every biological system. NO regulates functions of numerous proteins through S-nitrosylation, the covalent addition of NO to cysteine thiol. Through the study of S-nitroso-glutathione reductase (GSNOR), the key protein for de-nitrosylation in cells, Dr. Liu and colleagues have demonstrated that S-nitrosylation and its deactivation exert critical functions in systematic inflammation, asthma, cancer, and many other physiological and pathological processes.

GSNOR and asthma  It has been demonstrated with GSNOR-deficient (GSNOR-/-) mice that increased S-nitrosylation from GSNOR deficiency in a model of allergic asthma does not affect immune responses but abolishes airway hyperresponsiveness. Dr. Liu’s laboratory is investigating the mechanism of S-nitrosylation-dependent protection to understand a key question in asthma: How do allergic immune responses cause airway hyperresponsiveness?

GSNOR and carcinogenesis   NO is implicated in tumorigenesis by much circumstantial evidence, but little is known definitively about the mechanisms through which endogenous NO might regulate the behavior of pre-cancerous or cancerous cells. Using GSNOR-/- mice Dr. Liu’s laboratory has discovered that dysregulated S-nitrosylation from GSNOR deficiency inactivates a key DNA repair system and promotes liver cancer (Science Translational Medicine 2:19ra13, 2010). Investigation is underway to expend the findings and to further elucidate molecular mechanisms.

New pathways in NO deactivation   Dr. Liu and colleagues have demonstrated that GSNOR and flavohemoglobin, the major NO-consuming enzyme, operate together to regulate NO bioactivities and to protect against NO-related toxicity in the yeast Saccharomyces cerevisia. They are employing the yeast model to elucidate the roles of additional, novel genes that are required for protection against NO-related toxicity. Homologue proteins are also investigated in animals.

Selected Publications:

  1. Liu L , Yan Y, Zeng M, Zhang J, Hanes MA, Ahearn G, McMahon TJ, Dickfeld T, Marshall HE, Que LG, Stamler JS (2004). Essential roles of S -nitrosothiols in vascular homeostasis and endotoxic shock. Cell 116:617-628.
  2. Que LG, Liu L , Yan Y, Whitehead GS, Gavett SH, Schwartz DA, Stamler JS (2005). Protection from experimental asthma by an endogenous bronchodilator. Science 308:1618-1621.
  3. Choudhry S, Que LG, Yang Z, Liu L, Eng C, Kim SO, Kumar G, Thyne S, Chapela R, Meade K, WatsonHG, LeNoir M, Rodriquez-Santana JR, Rodriguez-Cintron W, Avila PC, Stamler JS, Burchard EG (2010). GSNO Reductase and β2 Adrenergic Receptor Gene-gene Interaction: Bronchodilator Responsiveness to Albuterol. Pharmacogenetics and Genomics 20:351-8.
  4. Wei W, Li B, Hanes MA, Kakar S, Chen X, Liu L (2010). Deficiency of S-Nitrosoglutathione Reductase Impairs DNA Repair and Promotes Hepatocarcinogenesis. Science Translational Medicine 2: 19ra13.
  5. Yang Z, Wang Z, Doulias P, Wei W, Ischiropoulos H, Locksley RM, Liu L (2010). Lymphocyte development requires S-nitrosoglutathione reductase. J Immunol, 185:6664-6669.
  6. Wei W, Yang Z, Tang CH, Liu L (2011). Targeted deletion of GSNOR in hepatocytes of mice causes nitrosative inactivation of O6-alkylguanine-DNA alkyltransferase and increased sensitivity to genotoxic diethylnitrosamine. Carcinogenesis 32:973-977.
  7. Na B, Huang ZM, Wang Q, Qi ZX, Tian YJ, Lu CC, Yu JW, Hanes MA, Sanjay Kakara S, Huanga EJ, Ou JHJ, Liu L ‡,*, and Yen TSB‡,† (2011). Transgenic Expression of Entire Hepatitis B Virus in Mice Induces Hepatocarcinogenesis Independent of Chronic Liver Injury. PLoS One 6:e26240.
    ‡co-senior author; *Corresponding author; †Deceased August 31, 2009.
  8. Tang CH, Wei W, Liu L (2012). Regulation of DNA Repair by S-Nitrosylation. Biochim Biophys Acta 1820:730–735.
  9. Ozawa K*, Tsumoto H, Wei W, Tang CH, Komatsubara AT, Kawafune H, Shimizu K, Liu L*, Tsujimoto G (2012). Proteomic analysis of the role of S-nitrosoglutathlone reductase in lipopolysaccharide-challenged mice. Proteomics 12, 2024-2035. *Corresponding author.
  10. Leung J, Wei W, Liu L (2013). S-nitrosoglutathione reductase deficiency increases mutagenesis from alkylation in mouse liver. Carcinogenesis (in press).
  11. Tang CH, Wei W, Hanes MA, Liu L (2013). Hepatocarcinogenesis driven by GSNOR deficiency is prevented by iNOS inhibition. Cancer Research (in press).