mghlogoMIBRClogomghfc-logohms-logo

MIBRC Research

Principal Investigators:

Bobby Cherayil, MD

Alessio Fasano, MD

Verena Göbel, MD

Bryan Hurley, PhD

Hai Ning Shi, DVM, PhD >>

W. Allan Walker, MD

Collaborators:

Beth McCormick, PhD

Hans-Christian Reinecker, MD

Research Lab

Hai Ning Shi, DVM, PhD

Associate Professor of Pediatrics, Havard Medical School

Work Phone: (617) 726-4173
Work FAX: (617) 726-4172
Work eMail: shiha@helix.mgh.harvard.edu

Research team:

Chienwen Su, PhD, Instructor of Pediatrics
Mei Zhang, MD, Post-Doctoral Fellow
Libo Su, DVM, PhD, Student
Guilian Yang, DVM, PhD, Post-Doctoral Fellow
Yujuan Qi, MD, PhD, Post-Doctoral Fellow

Helminth Infections and Mucosal Response

The inverse correlation between exposure to helminthes and the incidence of certain immune-mediated diseases, including inflammatory bowel diseases (IBD), has been evidenced from epidemiological studies. The distribution of several pathogenic helminth infections coincides geographically with many devastating microbial diseases, such as HIV, malaria, and tuberculosis. Infections with intestinal helminths and enteric bacterial pathogens, such as enteropathogenic Escherichia coli (EPEC), continue to be a major global health threat, especially for children.

Shi Mouse
Mouse colonic epithelial junction.

However, the nature of the interaction and the exact mechanism by which helminth modulates the host’s response to concurrent pathogens are still unclear. Dr. Hai Ning Shi’s laboratory investigates the role of helminth parasites in evoking a T helper cell intestinal response and its effect on bacterial invasion. He is particularly interested in exploring the mechanisms by which the helminth parasite modulates intestinal mucosal response to enteric bacteria and bacteria-associated intestinal inflammation using a co-infection model system.

This system involves two murine enteric infectious agents that induce distinct Th responses: (i) the helminth Heligmosomoides polygyrus (Th2) and (ii) the Gram-negative bacterium Citrobacter rodentium (Th1). He has shown that helminth co-infection results in an impaired host protection and the development of more severe C. rodentium-mediated intestinal inflammation by a STAT 6 (Th2) dependent mechanism.

He has also shown that the helminth modulates host response via the effect of dendritic cells. In collaboration with Dr. Allan Walker, Dr. Shi also examines the impact of intestinal colonization of bacteria (probiotics) during early life on the development and regulation of mucosal T cell responses (Th1, Th2 and T regs) and explores the mechanisms by which probiotics modulate host protection against enteric pathogens.

Dr. Shi's lab.

Using both in vivo and in vitro approaches, he also examines and defines the conditions under which dysregulation of intestinal mucosal response to luminal antigens triggers the development of intestinal inflammatory responses that ultimately result in chronic inflammatory disease. His research will provide greater insight about how intestinal microorganisms may alter the regulatory mechanisms of mucosal immunity, which may be instrumental in the establishment of effective preventive and therapeutic approaches for the treatment of Th1- and Th2-mediated diseases and for the design of effective intestinal vaccines.