Curriculum Vita
Hai Ning Shi, DVM, PhD
Assistant Professor of Pediatrics
GENERAL INFORMATION
Date Prepared: October 18, 2005
Name: Hai Ning Shi
Office Address:
Mucosal Immunology Laboratory
Massachusetts General Hospital East, Room 3504
Building 114, 16th Street
Charlestown, MA 02129
Phone: (617) 726-4173
Fax: (617) 726-4172
E-mail: shiha@helix.mgh.harvard.edu
Education:
1982 D.V.M. Department of Veterinary Medicine, Qinghai University, School of Animal Science and Veterinary Medicine, China
1996 Ph.D. Institute of Parasitology, McGill University, Montreal, Canada
Postdoctoral Training:
1996-1999 Postdoctoral Fellow, Mucosal Immunology Laboratory, Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital and Harvard Medical School
Academic Appointments:
1982-1986 Research Fellow, Institute of Veterinary Medicine, Academy of Animal Science and Veterinary Medicine, Qinghai, China
1986-1989 Research Associate (Lecturer), Institute of Veterinary Medicine, Academy of Animal Science and Veterinary Medicine, Qinghai, China
1991-1996 Research Assistant & Ph.D. Student, Institute of Parasitology, McGill University, Canada
1996-1999 Postdoctoral Fellow, Mucosal Immunology Laboratory Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital & Harvard Medical School
1999-2002 Instructor in Pediatrics, Harvard Medical School
2002- Assistant Professor of Pediatrics, Harvard Medical School
Hospital or Affiliated Institution Appointments:
1999- Assistant Immunologist, Massachusetts General Hospital
Other Professional Positions and Major Visiting Appointments
1990-1991 Visiting Scientist, Institute of Parasitology, McGill University, Canada
Professional Societies:
1998- American Association of Immunologists
2001- American Gastroenterology Association
2005- American Society for Microbiology
2005- Society for Mucosal Immunology
Awards and Honors:
1990 Visiting Scientist Fellowship, State Education Commission of The People's Republic of China
1990-1992 Differential Fee Waiver Awards for International Students, The Faculty of Graduate Studies and Research, McGill University, Montreal, Canada
1992 Summer Bursary, McGill University
1992 Graduate Student Travel Award, Canadian Society of Zoology
1993 Lynden Laird Lyster Memorial Award in Parasitology, McGill University
1994 Wyeth Graduate Student Award, The Canadian Society of Nutritional Sciences and The Canadian Federation of Biological Societies
1998 Research Fellowship Award, Crohn's & Colitis Foundation of America
2001 Career Development Award, Crohn’s & Colitis Foundation of America
2003- First Award, Crohn’s & Colitis Foundation of America
2003- NIH/KO-1 Award
RESEARCH, TEACHING AND CLINICAL CONTRIBUTIONS
Narrative Report:
My research is focused on the pathogenesis and immune regulation of intestinal inflammation. We are particularly interested in exploring the mechanisms by which 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). The distribution of several pathogenic helminth infections coincides geographically with many devastating microbial diseases, such as HIV, malaria and tuberculosis. Evidence from epidemiological studies indicates an inverse correlation between exposure to helminths and the incidence of certain immune-mediated diseases (the hygiene hypothesis), including inflammatory bowel diseases (IBD). A more comprehensive understanding of immunoregulation in the intestinal mucosa may provide new information for establishing more effective preventive and therapeutic approaches to the treatment of both Th1 and Th2-mediated diseases, and for the design of effective intestinal vaccines.
The intestinal tract harbors the largest concentration and diversity of bacterial antigens in the body. It is extremely important for the intestinal epithelial cells and the intestinal mucosal immune system to discriminate between pathogenic and non-pathogenic bacteria and to generate an appropriate response, maintaining a state of homeostasis with the normal microbial flora or initiating inflammatory responses to pathogens. Our research also examines and defines the conditions under which dysregulation of intestinal mucosal response to luminal antigen triggers the development of an intestinal inflammatory response that results ultimately in chronic intestinal inflammatory disease, using both in vivo and in vitro approaches. Specifically, we explore the role of bacterial products as triggering agents to alter intestinal barrier function and mucosal immune function. We also study the impact of intestinal colonization of probiotics at early life on the development and regulation of mucosal T cell responses (Th1, Th2 and T regs) and explore the mechanisms by which probiotics modulate host protection against enteric pathogens. Our 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 immune mediated disorders.
Funding Information
1998-2001 Research Fellowship Award, Crohn's and Colitis Foundation of America. “Altered responsiveness to food proteins in the presence of mucosal infection”
1999 NIH/Clinic Nutrition Research Center at Harvard/Pilot Feasibility Project. Co-P.I.“Influence of helminth infection on food allergy”
2001 NIH/MGH Center for the Study of Inflammatory Bowel Disease Pilot Feasibility Study P.I.“ Triggering intestinal inflammation”
1/2001-12/2002 Career Development Award, Crohn’s and Colitis Foundation of America. P.I.“Triggering intestinal inflammation”
2000-2003 Hood Foundation Grant, Charles H. Hood Foundation P.I. “The induction of intestinal inflammation: Role of luminal bacterial antigen”
2003- First Award, Crohn’s & Colitis Foundation of America. P.I. “Investigation of epithelial cell-commensal bacterial interaction in intestinal inflammation”
2003 NIH/KO1 P.I. “Triggering intestinal inflammation”
C. Teaching:
1. Local Contributions
a. Courses
Course Director: Molecular Cell Biology, Pediatric GI Fellow and Student Course (June-Dec. 2003; June-September 2004)
Tutor: Immunology, Microbiology and Infectious Disease, Harvard Medical School. 2001
b. Advisory and supervisory responsibilities:
2001-current: Supervise three postdoctoral fellows, two undergraduate students, and two research technologists.
2002-2004 Chien-chang Chen, MD (Research Fellow). Current position: Assistant Professor at Chang Gung University and Chang Gung Children's Hospital, Taiwan
2002-2003 Weishu Zhu, MD (Research Fellow) Current position: Research Technologist at Mucosal Immunology Lab, MGH
2001-2004 Steve Louie, Research technologist
2004 Sonia Miller, Undergraduate student from DePauw University. Current position: Medical Student at Harvard Medical School.
2005 Deke Huntley, Research technologist.
2005 Aliese Sarkissian, Undergraduate student from DePauw University.
2005 Ondulla Foye-Jackson, Ph.D (Postdoctoral fellow)
2. Regional, National and International Contributions:
1991 Workshop presentation. American Society of Parasitologists, Madison, Wisconsin
1992 Mini workshop presentation. Canadian Society for Immunology, Montreal, Canada
1992 Workshop presentation. Canadian Society of Zoology. Nova Scotia, Canada
1993 Graduate Student presentation. American Society of Tropical Medicine and Hygiene, American Society of Parasitologists, Atlanta, Georgia
1994 Graduate Student presentation. Canadian Federation of Biological Societies. Montreal, Canada
1994 Workshop presentation. American Society of Parasitologists, Ft Collin, CO.
1999 Invited seminar. Qinghai University, School of Veterinary Medicine, Xining, China
2000 Workshop presentation. American Association of Immunologists, Seattle, Washington
2001 11th Annual Symposium presentation. Center for the Study of Inflammatory Bowel Disease at Mass. General Hospital. Boston.
2003 Invited lecture: Hospital of Qinghai Medical School, Xining City. PR. China.
2003 Invited lecture. Qinghai University, Xining, China.
2005. Invited lecture. Qinghai Academy of animal science and Veterinary Medicine. Qinghai, China.
2005 Invited lecture. Qingahi University Medical School, Qinghai, China.
2005 Invited lecture. Qinghai University School of Veterinary Medicine. Qinghai, China
2005 Invited lecture. National Institute of Biological Science, Beijing, China.
BIBLIOGRAPHY
Original Articles
1. Shi HN, Scott ME, Stevenson MM, Koski KG. Zinc deficiency impairs T cell function in mice with primary infection of Heligmosomoides polygyrus (Nematoda). Parasite Immunology. 1994: 16: 339-350.
2. Hai Ning Shi, Marilyn E. Scott, Kristine G. Koski, Marjolaine Bouley and Mary M. Stevenson. Energy restriction and severe zinc deficiency influence development, survival and reproduction of Heligmosomoides polygyrus (Nematoda) during primary and challenge infections in mice. Parasitology. 1995; 110: 599-609.
3. Hai Ning Shi, Kristine G. Koski, Mary M. Stevenson and Marilyn E. Scott. Zinc deficiency and energy restriction modify immune responses in mice during both primary and challenge infection with Heligmosomoides polygyrus (Nematoda). Parasite Immunology. 1997;19: 363-373.
4. Hai Ning Shi, Marilyn E. Scott, Kristine G. Koski and Mary M. Stevenson. Zinc deficiency and concurrent energy restriction reduce the functions of murine T cells and antigen-presenting cells during a gastrointestinal nematode infection. Journal of Nutrition. 1997; 128: 20-27.
5. Hai Ning Shi, Christian Ingui, Ingrid Dodge and Cathryn Nagler-Anderson. A helminth induced mucosal Th2 response alters non-responsiveness to oral administration of a soluble antigen. Journal of Immunology. 1998, 160: 2449-2455.
6. Hai Ning Shi, Michael J. Grusby and Cathryn Nagler-Anderson. Orally induced peripheral nonresponsiveness is maintained in the absence of functional Th1 or Th2 cells. Journal of Immunology. 1999, 162; 5143-5148.
7. James G. Fox, Paul Beck, Charles A Dangler, Mark T. Whary, Timothy C. Wang, Hai Ning Shi and Cathryn Nagler-Anderson. Concurrent enteric infection modulates inflammation, gastric immune responses, and reduces helicobacter-induced gastric atrophy. Nature Medicine. 2000; 6 (45): 536-542.
8. Hai Ning Shi, Hao Yuan Liu and Cathryn Nagler-Anderson. Enteric infection acts as an adjuvant for the response to a model food antigen. Journal of Immunology. 2000, 165:6174-6182.
9. Bashir ME, Andersen P, Fuss IJ, Shi HN, Nagler-Anderson C. An enteric helminth infection protects against an allergic response to dietary antigen. Journal of Immunology. 2002, 169(6):3284-3292.
10. Bashir MEH, Louie S., Shi H.N. and Nagler-Anderson C. TLR4 signaling by intestinal microbes influences susceptibility to food allergy. 2004. Journal of Immunology. 172(11): 6978-87.
11. Whary MY, Z He, HJ White, HN Shi, C. Nagler-Anderson and JG Fox. Heligmosomoides polygyrus parasitism attenuates the progression of typhlocolitis and epithelial hyperplasia in the IL-10-/- mouse model of Helicobacter hepaticus-associated inflammatory bowel disease. 2004. Submitted.
12. Moran ST, Cariappa A, Liu H, Boboila C, Shi HN, Holland PM, Peschon JJ, Pillai S. Protein kinase C-associated kinase is not required for the development of peripheral B lymphocyte populations. Mol Immunol. 2005.
13. Chien-Chang Chen, Hai Ning Shi and Allan Walker. Precolonization with the Probiotic Lactobacillus acidophilus early in life effectively inhibits murine Citrobacter rodentium colitis. Pediatric Research. 2005. 58 (6): 1185-1191.
14. Annaiah Cariappa, Irina B. Mazo, Catharine Chase, Hai Ning Shi, Haoyuan Liu, Qian Li, Harris Rose, Harry Leung, Bobby J. Cherayil, Paul Russell, Ulrich von Andrian, and Shiv Pillai. Perisinusoidal B Cells in the Bone Marrow Participate in T-Independent Responses to Blood-Borne Microbes. Immunity. 2005. 23 (4): 397-407.
15. Chien-Chang Chen, Steve Louie, Beth McCormick, Allan Walker and Hai Ning Shi. Concurrent infection of an intestinal helminth parasite impairs host resistance to enteric Citrobacter rodentium and enhances Citrobacter-induced colitis in mice. Infection and Immunity. 2005. 73 (9): 5468-5481.
16. Tor C. Savidge, Paul G. Newman, Wei-Hua Pan, Mei-Qian Weng, Hai Ning Shi, Beth A. McCormick, Andrea Quaroni, W. Allan Walker. Lipopolysaccharide-induced human enterocyte tolerance to cytokine-mediated interleukin-8 production may occur independently of TLR-4/MD-2 signalling. Pediatric Research. 2006. 59 (1).
17. Chien-Chang Chen, Steve Louie, Beth McCormick, Allan Walker and Hai Ning Shi. Helminth primed dendritic cells alter the host response to enteric bacterial infection. The Journal of Immunology. 2006. 176:
Reviews, Chapters, and Editorials:
1. Hai Ning Shi and Cathryn Nagler-Anderson. Mucosal T cell responses to enteric infection. Current Opinion in Gastroenterology, 1999, 15: 529-533.
2. Cathryn Nagler-Anderson and Hai Ning Shi. The induction of peripheral non- responsiveness to orally administered soluble antigens. Critical Reviews in Immunology 2001, 21:121-131.
3. Hai Ning Shi and W. Allan Walker. T helper cell subclasses and clinical disease states. Current Opinion in Gastroenterology. 2002, 18(6): 711-716.
5. Hai Ning Shi and W. Allan Walker. Bacterial colonization in the developing gastrointestinal tract: Role in the pathogensis of intestinal diseases. Bioscience Microflora. 2004, 23(2):55-65.
6. Shi HN, Walker A. Bacterial colonization and the development of intestinal defences. Can J Gastroenterol. 2004. 18(8): 493-500.
Conference Abstracts:
1. Marilyn E. Scott, Farzaneh Jalili and Hai Ning Shi. Comparison of resistance to Heligmosomoides polygyrus trickle infection in C57BL/6 and Balb/C mice. 66th Annual Meeting of The American Society of Parasitologists (Madison, Wisconsin), 1991: 138.
2. Hai Ning Shi, Mary M. Stevenson, Kristine G Koski and Marilyn E. Scott. Impairment of DTH and cytokine production in zinc deficient mice infected with Heligmosomoides polygyrus. Sixth Spring Meeting of The Canadian Society for Immunology (Mont Rolland, Montreal, Canada), 1992; 2.14.
3. Hai Ning Shi, Marilyn E. Scott, Mary M. Stevenson and Kristine G. Koski. Effects of zinc deficiency on Heligmosomoides polygyrus in mice. Canadian Society of Zoology (Nova Scotia, Canada), 1992.
4. Hai Ning Shi, Marilyn E. Scott, Mary M. Stevenson and Kristine G. Koski. The role of zinc in host immunity and Heligmosomoides polygyrus infection. XIIIth International Congress for Tropical Medicine and Malaria (Jomtien, Pattaya, Thailand), 1992.
5. Hai Ning Shi, Marilyn E. Scott, Mary M. Stevenson and Kristine G. Koski. Zinc deficiency affects Heligmosomoides polygyrus during both primary and challenge infection in mice. Joint Meeting of The American Society of Tropical Medicine and Hygiene and American Society of Parasitologists (Atlanta, USA), 1993; 152.
7. Hai Ning Shi, Mary M. Stevenson, Marilyn E. Scott and Kristine G. Koski. Functional studies and cytometric analysis of splenic T cells of zinc deficient mice infected with Heligmosomoides polygyrus. Eighth Spring Meeting of the Canadian Society of Immunology (Le Chantecler, Sainte-Adele, Quebec, Canada), 1994; 2.
8. Hai Ning Shi, Marilyn E. Scott, Mary M. Stevenson and Kristine G. Koski. Effects of zinc deficiency and energy restriction on host immunity on an intestinal nematode infection of mice. Canadian Federation of Biological Societies, 37th Annual Meeting (Montreal, Canada), 1994: 228.
9. Hai Ning Shi, Marilyn E. Scott, Mary M. Stevenson and Kristine G. Koski. Experimental zinc deficiency: effect on antibody responses in mice with Heligmosomoides polygyrus infection. Annual Meeting of the American Society of Parasitologists (FT. Collins, CO. USA), 1994.
10. Hai Ning Shi, Mary M. Stevenson, Marilyn E. Scott and Kristine G. Koski. Effects of zinc deficiency on response of T cells and antigen-presenting cells to Heligmosomoides polygyrus in mice. The 9th International Congress of Immunology (San Francisco, CA), 1995.
11. Hai Ning Shi, Christian Ingui, Ingrid Dodge and Cathryn Nagler-Anderson. A helminth induced mucosal Th2 response alter non-responsiveness to oral administration of a soluble antigen. Experimental Biology 1998 (San Francisco, CA), FASEB Journal 1998, 12:A3463.
12. Hai Ning Shi, Hao Yuan Liu and Cathryn Nagler-Anderson. Enteric infection acts as a mucosal adjuvant for the response to oral antigens. Annual Meeting of American Gastroenterology Association (Florida), 1999. Gastroenterology 116, A818.
13. Fox, J.G., P. Beck, C. A. Dangler, T. Wang, M. T. Whary, H. N. Shi and C. Nagler-Anderson. Solving the African enigma: coinfection with an intestinal parasite modulates inflammation and reduces gastric atrophy in a mouse model of Helicobacter infection. 10th International workshop on Campylobacter, Helicobacter and related organisms, 1999
14. Fox, J. G., P. Beck, C. A. Dangler, T. Wang, M. T. Whary, H.N. Shi and C. Nagler-Anderson. Modulation of the Th1/Th2 response with Heligmosomoides polygyrus and Helicobacter felis coinfection in mice: an animal model to study the "African enigma". 10th International workshop on Campylobacter, Helicobacter and related organisms, 1999.
15. Hai Ning Shi, Hao Yuan Liu and Cathryn Nagler-Anderson. Adjuvant effect of intestinal helminth infection on the response to a model food antigen. Immunology 2000 (AAI, Seattle, Washington, May 12-16, 2000). The FASEB Journal, Vol. 14. No.6, 183.5
16. Fox, J. G., C. A. Dangler, P. Beck, T. Wang, M.T. Whary, H.N. Shi and C. Nagler-Anderson. Intestinal helminth infection modulates inflammation and reduces gastric atrophy in a mouse model of Helicobacter infection. Annual Meeting of the American Gastroenterological Association (San Diego, CA), 2000. Gastroenterology 118, 1226.
17. Bashir M E.H., H.N. Shi, P. Andersen, E.I. Melendro and C. Nagler-Anderson. Enteric helminth infection does not induce an allergic response to a food antigen. Annual Meeting of American Gastroenterology Association (DDW), Atlanta, 2001.
18. Whary M.T., H.N. Shi, H. White, C. Nagler-Anderson and J.G. Fox. Th2 response to the helminth Heligmosomoides polygyrus reduce Th1-promoted epithelial hyperplasia in a mouse model of Helicobacter hepaticus-associated inflammatory bowel disease (IBD). Annual Meeting of American Gastroenterology Association (DDW), Atlanta, 2001.
19. Shi, H.N., M.E.H. Bashir, P. Andersen, E.I. Melendro and C. Nagler-Anderson. Impact of intestinal helminth infection on the host allergic response to dietary antigens. Fifth Annual Woods Hole Immunoparasitology Meeting, 2001
20. M. T. Whary, HN. Shi, H. White, C. Nagler-Anderson, J. G. Fox. Th2 Responses to the Helminth Heligmosomoides polygyrus Reduce Th1-Promoted Epithelial Hyperplasia in a Mouse Model of Helicobacter hepaticus-Associated Inflammatory Bowel Disease (IBD). European Helicobacter Study Group, Strasbourg Workshop 2001.
21. Donald Smith, Onyinye Iweala, Hai Ning Shi and Cathryn Nagler-Anderson. Presentation of model immunogenic and tolerogenic antigens by the gut associated lymphoid tissue. Keystone Symposia. CO. 2002
22. Cathryn Nagler-Anderson, Mohamed E.H. Bashir, Emma I. Melendro, Donald Smith, Onyinye Iweala and Hai Ning Shi. Regulation of tolerance and immunity in the intestinal mucosa. Keystone Symposia. CO. 2002
23. Cathryn Nagler-Anderson, Hai Ning Shi, Weishu Zhu, Steve Louie, Mohamed Elfatih B. Bashir. TLR-4 signaling by intestinal microbes influences susceptibility to food allergy. AAI, Washington D.C., April 17-21, 2004.
24. Chien-Chang Chen, Steve Louie, Weishu Zhu, Beth McCormick, Allan Walker and Hai Ning Shi. Intestinal helminth infection impairs host resistance and enhances colonic pathology during concurrent Citrobacter rodentium infection in mice. Annual Meeting of American Gastroenterology Association (DDW, New Orleans, LA.). Gastroenterology. 126(4). Suppl2. M1066, 2004.
25. Chien-Chang Chen, Steve Louie, Allan Walker and Hai Ning Shi. Precolonization with the Probiotic Lactobacillus acidophilus early in life effectively inhibit murine Citrobacter rodentium colitis. Annual Meeting of American Gastroenterology Association (DDW, Chicago). May 14-19, 2005.
Ph. D. Thesis:
Hai Ning Shi. Interactions among zinc deficiency, energy restriction, immunity and Helgmosomoides polygyrus (Nematoda) infection in mice. Ph. D. Thesis. Montreal, Canada. McGill University. 1996, 249 pages.
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