Associate Professor
Animal Molecular Biology

EDUCATION/TRAINING

PROFESSIONAL EXPERIENCE

HONORS AND AWARDS

STUDENTS' ACHIEVEMENTS

PROFESSIONAL AFFILIATIONS

RESEARCH INTEREST

Humans and animals have evolved many strategies to recognize and respond to pathogens. A growing body of evidence indicates that pathogens are recognized by hosts and activate the host immune system primarily through a group of Toll-like receptors (TLRs). These TLRs serve as receptors for a variety of pathogens, including bacteria, yeast and viruses and play a key role in triggering host innate immune responses. One of the most important mechanisms of innate immunity is the endogenous production and elaboration of antimicrobial peptides, also known as peptide antibiotics or natural antibiotics. These natural antibiotics are ubiquitously produced by host immune cells. Strikingly, they are capable of killing a broad spectrum of microorganisms with extremely low risk of developing resistance, a desirable feature for a new generation of antimicrobial drugs.

Our laboratory is dedicated to delineating molecular mechanisms of pathogen recognition and host defense with an ultimate goal to devise more effective strategies to enhance disease resistance of humans and animals with less or no reliance on the use of conventional antibiotics. Experimental approaches include the state-of-the-art technologies in molecular biology, immunology, genomics, proteomics, and bioinformatics. Our research could potentially lead to the discovery of novel genes that are critically involved in innate host defense and disease resistance enabling prevention and control of infectious diseases. Currently we are focusing on:

• Potential of antimicrobial peptides as antibiotic alternatives in infectious disease control and preharvest food safety by carrying out systematic structure-function relationship studies involving the use of antibacterial and antiviral assays, recombinant protein techniques, NMR spectroscopy, molecular modeling, and in vivo gene delivery.

• Molecular mechanisms of antimicrobial peptides in the pathogenesis of inflammatory bowel disease by employing a variety of cell signaling and functional genomics approaches.
  

• Functional genomics approaches to the bovine respiratory disease complex by studying and manipulating host-pathogen interactions using DNA microarray and RNA interference.

SELECTED PUBLICATIONS

1. Zhang, G., C.R. Ross, S.S. Dritz, J.C. Nietfeld, and F. Blecha (1997) Salmonella infection increases porcine antibacterial peptide concentrations in serum. Clinical and Diagnostic Laboratory Immunology 4: 774-777. [PDF]
   
   
2. Zhang, G., H. Wu, J. Shi, T. Ganz, C.R. Ross, and F. Blecha (1998) Molecular cloning and tissue expression of porcine b-defensin-1. FEBS Letters 424: 37-40. [PDF]
   
   
3. Wu, H., G. Zhang, C.R. Ross, and F. Blecha (1999) Cathelicidin gene expression in porcine tissues: roles in ontogeny and tissue specificity. Infection and Immunity 67: 439-442. [PDF]
   
   
4. Zhang, G., H. Hiraiwa, H. Yasue, H. Wu, C.R. Ross, D. Troyer, and F. Blecha (1999) Cloning and characterization of the gene for a new epithelial b-defensin: genomic structure, chromosomal localization, and evidence for its constitutive expression. Journal of Biological Chemistry 274: 24031-24037. [PDF]
   
   
5. Shi, J., G. Zhang, H. Wu, C.R. Ross, F. Blecha, and T. Ganz (1999) Porcine epithelial b-defensin 1 is expressed in the dorsal tongue at antimicrobial concentrations. Infection and Immunity 67: 3121-3127. [PDF]
   
   
6. Zhang, G., H. Wu, C.R. Ross, J.E. Minton, and F. Blecha (2000) Cloning of porcine NRAMP1 and its induction by lipopolysaccharide, tumor necrosis factor-a, and IL-1b: role of CD14 and mitogen-activated protein kinases. Infection and Immunity 68: 1086-1093. [PDF]
   
   
7. Zhang, G., C.R. Ross, and F. Blecha (2000) Porcine antimicrobial peptides: new prospects for ancient molecules of host defense. Veterinary Research 31: 277-296. [PDF]
   
   
8. Wu, H., G. Zhang, C.R. Ross, J.E. Minton, and F. Blecha (2000) Regulation of cathelicidin gene expression: induction by lipopolysaccharide, interleukin-6, retinoic acid, and Salmonella enterica serovar typhimurium infection. Infection and Immunity 68: 5552-5558. [PDF]
   
   
9. Zhang, G., and S. Ghosh (2000) Molecular mechanisms of NF-kB activation induced by lipopolysaccharide through Toll-like receptors. Journal of Endotoxin Research 6: 453-457. [PDF]
   
   
10. Zhang, G., and S. Ghosh (2001) Toll-like receptor-mediated NF-kB activation: a phylogenetically conserved paradigm in innate immunity. Journal of Clinical Investigation 107: 13-19. [PDF]
    
    
11. Zhang, G., and S. Ghosh (2002) Negative regulation of Toll-like receptor-mediated signaling by Tollip. Journal of Biological Chemistry 277: 7059-7065. [PDF]
    
    
12. Zhang, D., G. Zhang, M.S. Hayden, M.S. Greenblatt, C. Bussey, R.A. Flavell, and S. Ghosh (2004) A Toll-like receptor that prevents infection by uropathogenic bacteria. Science 303: 1522-1526. [PDF]
    
    
13. Zhang, G. (2004) Molecular biology: animal. In: Encyclopedia of Animal Science; Pond, W.G., Bell, A.W. Eds.; Marcel Dekker, Inc., New York. pp. 653-656. [PDF]
    
    
14. Xiao, Y, A.L. Hughes, J. Ando, Y. Matsuda, J.F. Cheng, D. Skinner-Noble, and G. Zhang. (2004) A genome-wide screen identifies a single b-defensin gene cluster in the chicken: implications for the origin and evolution of mammalian defensins. BMC Genomics 5: 56. [PDF]
    
    
15. Patil, A., A.L. Hughes, and G. Zhang. (2004) Rapid evolution and diversification of mammalian a-defensins as revealed by comparative analysis of rodent and primate genes. Physiological Genomics 20: 1-11. [PDF]
    
    
16. Patil, A.A., Y. Cai, Y. Sang, F. Blecha, and G. Zhang (2005) Cross-species analysis of the mammalian ß-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract. Physiological Genomics 23: 5-17. [PDF]
    
    
17. Sang, Y., A. A. Patil, G. Zhang, C. R. Ross, and F. Blecha (2006) Bioinformatic and expression analysis of novel porcine b-defensins. Mammalian Genome 17: 332-339. [PDF]
    
    
18. Hasenstein, J. R., G. Zhang, and S. J. Lamont. (2006) Analyses of five Gallinacin genes and the Salmonella enterica serovar Enteritidis response in poultry. Infection and Immunity 74: 3375-3380. [PDF]
    
    
19. Xiao, Y., Y. Cai, Y.R. Bommineni, S.C. Fernando, O. Prakash, S.E. Gilliland, and G. Zhang (2006) Identification and functional characterization of three chicken cathelicidins with potent antimicrobial activity. Journal of Biological Chemistry 281: 2858-2867. [PDF]
    
    
20. Xiao, Y., H. Dai, Y.R. Bommineni, J. Soulages, Y.-X. Gong, O. Prakash, and G. Zhang (2006) Structure-activity relationships of fowlicidin-1, a cathelicidin antimicrobial peptide in chicken. FEBS Journal 273: 2581-2593. [PDF]
    
    
21. Aono, S., C. Li, G. Zhang, R. J. Kemppainen, J. Gard, W. Lu, X. Hu, D. D. Schwartz, E. E. Morrison, C. Dykstra, and J. Shi. (2006) Molecular and functional characterization of bovine b-defensin-1. Veterinary Immunology and Immunopathology 113: 181-190. [PDF]
    
    
22. Lynn, D. J., R. Higgs, A. T. Lloyd, C. O'Farrelly, V. Herve-Grepinet, Y. Nys, F. S. Brinkman, P. L. Yu, A. Soulier, P. Kaiser, G. Zhang, and R. I. Lehrer. (2007) Avian beta-defensin nomenclature: a community proposed update. Immunology Letters 110:86-89. [PDF]
    
    
23. Bommineni, Y.R., H. Dai, Y.-X. Gong, J.L. Soulages, S.C. Fernando, U. DeSilva, O. Prakash, and G. Zhang. (2007) Fowlicidin-3 is an a-helical cationic host defense peptide with potent antibacterial and lipopolysaccharide-neutralizing activities. FEBS Journal 274: 418-428. [PDF]
    
    
24. Sang, Y., M. Teresa Ortega, K. Rune, W. Xiau, G. Zhang, J. L. Soulages, G. H. Lushington, J. Fang, T. D. Williams, F. Blecha, and T. Melgarejo. (2007) Canine cathelicidin (K9CATH): Gene cloning, expression, and biochemical activity of a novel pro-myeloid antimicrobial peptide. Developmental and Comparative Immunology (In press). [PDF]