John C. Hu.

John C. Hu

Department

Microbiology and Immunology

Thesis

PhD Thesis title: Enhancement of CD8+ T Cells by the Type II Heat-Labile Enterotoxins LT-IIb and LT-IIc (Completed 2015)

Residency

Internal Medicine, University at Buffalo

Undergraduate Education

Biomedical Sciences,
University at Buffalo

Thesis Advisor

The development of effective vaccines against infectious pathogens is one of modern medicine’s greatest achievements. However, most modern vaccines only elicit humoral responses and are unable to protect against diseases that require cellular immunity. Therefore, the development of vaccine strategies to produce both humoral and cellular immunity is of critical importance. Due to the lack of “danger signals” from modern subunit vaccines, adjuvants are required for robust cellular immune responses. The AB5 heat-labile enterotoxin family (HLT) that includes cholera toxin (CT), and the heat-labile enterotoxins type I (LT-I) and type II (LT-II) are among the most potent adjuvants available. While CT and LT-I have been shown to be potent stimulators of predominantly humoral and Th2 T cell responses in most vaccine preparations, the LT-IIs uniquely exhibit a balanced Th1/Th2 enhancement and a distinct cytokine profile that promote both humoral and cellular immunity. Our focus is to elucidate the mechanisms that are responsible for the unique immunological properties of these potent adjuvants. 

Publications

  • Greene, C. J., J. C. Hu, D. J. Vance, Y. Rong, L. Mandell, N. D. King-Lyons, M. Masso-Welch, N. J. Mantis, and T. D. Connell. Enhancement of humoral immunity by the type II heat-labile enterotoxin LT-IIb is dependent upon IL-6 and neutrophils. Journal of Leukocyte Biology 3A0415-153RR, 2016
  • Greene, C. J., L. R. Marks, J. C. Hu, R. Reddinger,  L. Mandell, H. Roche-Hakansson,  N. D. King-Lyons, T. D. Connell, and A. P. Hakansson. A novel strategy to protect against influenza-induced pneumococcal disease without interfering with commensal colonization. Infection and Immunity 84(6):1693-703. 2016
  • Hu, J. C., C. J. Greene, N.D. King-Lyons, and T. D. Connell. The Divergent CD8+ T Cell Adjuvant Properties of LT-IIb and LT-IIc, Two Type II Heat-Labile Enterotoxins, Are Conferred by Their Ganglioside-Binding B Subunits. PLoS ONE 10(11):e0142942. 2015
  • Hu, J. C., C. Mathias-Santos, C. J. Greene, N. D. King-Lyons, J. F. Rodrigues, G. Hajishengallis, L. C. Ferreira, and T. D. Connell. Intradermal administration of the Type II heat-labile enterotoxins LT-IIb and LT-IIc of enterotoxigenic Escherichia coli enhances humoral and CD8+ T cell immunity to a co-administered antigen. PLoS ONE 9:e113978. 2014
  • Greene, C. J., C. M. Chadwick, L. M. Mandell, J. C. Hu, J. M. O'Hara, R. N. Brey, 3rd, N. J. Mantis, and T. D. Connell. LT-IIb(T13I), a non-toxic type II heat-labile enterotoxin, augments the capacity of a ricin toxin subunit vaccine to evoke neutralizing antibodies and protective immunity. PLoS ONE 8:e69678. 2013
  • Nawar, H. F., N. D. King-Lyons, J. C. Hu, R. C. Pasek, and T. D. Connell. LT-IIc, a new member of the type II heat-labile enterotoxin family encoded by an Escherichia coli strain obtained from a nonmammalian host. Infection and Immunity 78:4705-4713. 2010
  • Hu, J. C., A. Bengrine, A. Lis, and M. S. Awayda. Alternative mechanism of activation of the epithelial Na+ channel by cleavage. The Journal of Biological Chemistry 284:36334-36345. 2009
  • Perry, M. J., J. Tait, J. C. Hu, S. C. White, and S. Medler. Skeletal muscle fiber types in the ghost crab, Ocypode quadrata: implications for running performance. The Journal of Experimental Biology 212:673-683. 2009
  • Aletta, J. M., and J. C. Hu. Protein arginine methylation in health and disease. Biotechnology Annual Review 14:203-224. 2008

Professional/Educational Meetings/Abstracts

  • Differential enhancement of CD8+ T cells by heat-labile enterotoxins LT-IIb and LT-IIc from enterotoxigenic Escherichia coli by intradermal administration American Physician Scientists Association 11th Annual Meeting, Chicago, IL. 2015
  • Intradermal administration of the type II heat-labile enterotoxins LT-IIb and LT-IIc of enterotoxigenic Escherichia coli enhances humoral and CD8+ T cell immunity to a co-administered antigen Upstate New York Immunology Conference, Bolton Landing, NY. 2014
  • Intradermal administration of type II heat-labile enterotoxins LT-IIb and LT-IIc of enterotoxigenic Escherichia coli enhances both humoral and cellular immunity with minimal inflammation Upstate New York Immunology Conference, Bolton Landing, NY. 2013
  • Identification and cloning of LT-IIc, a new Type II heat-labile enterotoxin of Escherichia coli UB Celebration of Excellence, Buffalo, NY. 2008

Awards/Honors

  • Gilbert D. Moore Fellowship
  • Panasci Technology Entrepreneurship Competition Winner
  • Gregory B. Jarvis Award

Medical School Activities

  • American Physician Scientists Association (APSA)
  • American College of Physicians (ACP)
  • Microbiology Club
  • Immunology Journal Club Coordinator
  • Good Neighbors Free Clinic

Extracurricular Interests

Photography, White Water Rafting/Kayaking, Food & Cooking, Computers & Technology