Laboratory Staff
Curriculum Vita

Bobby Cherayil, MD

Verena Göbel, MD

Ciarán Kelly, MD

Beth McCormick, PhD

Nanda
Nanthakumar, PhD

David Newburg, PhD

Harry Pothoulakis, MD

Hai Ning Shi, DVN, PhDW. Allan Walker, MD
Chief





Curriculum Vita

Nanda Nanthakumar, PhD
Assistant Professor of Pediatrics

GENERAL INFORMATION

Department of Pediatric Gastroenterology & Nutrition
Massachusetts General Hospital-East
Building 114 16th Street, Room 3650
Charlestown, MA 02129

Phone: 617-726 4180
Fax: 617-726 4172
Email: nanthaku@helix.mgh.harvard.edu

Education

1985 B.Sc., Zoology, University of Peradeniya, Sri Lanka
1992 Ph.D. Cell, Molecular and Developmental Biology, University of Houston

Positions and Honours:

Professional Experience:

9/85–9/86 Assistant Lecturer, University of Peradeniya, Peradeniya, Sri Lanka
9/86–8/87 Research Assistant, Open University, Colombo, Sri Lanka
9/87–1/89 Teaching Assistant, University of Houston, Houston, TX
1/89–2/93 Research Assistant, Baylor College of Medicine, Houston, TX
2/93–1/98 Research Associate Duke University Medical Center, Durham, NC
1/98 - Present Assistant Biologist, Massachusetts General Hospital, Boston, MA
1/98 - 2005 Instructor in Pediatrics, Harvard Medical School, Boston, MA
1999– Associate Member, Harvard Clinical Nutrition Research Center, Boston, MA
1999– Associate Member, Center for the Study of Inflammatory Bowel Disease (CSIBD), Boston, MA
2000– Associate Member, Dana-Farber Harvard Cancer Center (DFHCC), Boston, MA
2004 – Present Co-Director, Animal and Morphology Core, Harvard Clinical Nutrition Research Center, Boston
2005 – Present Assistant Professor in Pediatrics, Harvard Medical School, Boston, MA

Honors and Awards:

1986 – 1987 Natural Science Authority of Sri Lanka Research Fellowship
1987 Smithsonian Research Fellow, National Zoological Park, Washington D.C.
1989 Sigma Xi Grant-in-Aid Research Award
1989 American Gastroenterological Society Student Fellowship
1989 Teaching Excellence Award, Department of Biology, University of Houston
1989 College of Natural Science Endowment Scholarship, University of Houston
1990 Endocrine Society Student Fellowship
1994 - 1996 NIH-NRSA: Post Doctoral Fellowship
NIH: HD12437-S1 (Research Supplement for Under represented minorities-Nanda Nanthakumar)
Pilot Feasibility Grant: Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA
2004 Pilot Feasibility Grant: Harvard Clinical Nutrition Research center, MGH, Boston, MA

Memberships:

American Society for Cell Biology
American Society for Microbiology
American Gastroenterological Association
American Society for Mucosal Immunologist
American Association for the Advancement of Science

RESEARCH, TEACHING AND CLINICAL CONTRIBUTIONS

The adult human gastrointestinal tract is colonized by a community of more than 450 interdependent species of bacteria that are the major components of a stable but dynamic microbial ecosystem known as the gut microbiota. The gut microbiota are now becoming recognized as part of an important mutualist relationship in which both the microbes and humans benefit. Mutualist association requires cross communication (crosstalk) between the microbiota and the epithelial lining of the gut. My lab focuses on the interaction between gut epithelium and gut microbiota in the newborn, during the transition from milk to solid food, and in mature young adults.

Pioneer bacterial species induce expression of fucosylated cell surface glycans by mammalian gut epithelium. This enables colonization by additional fucose-adherent bacteria that direct the succession of microbial colonization toward the complex microbial ecosystem of the adult gut. We have identified a mechanism whereby pioneer bacterial species initiates communication with the gut epithelium at the genesis of colonization that leads to alteration of gene expression and generation of fucosylated gut surface.

Probiotics is another group of bacteria within our gut that, when present in sufficient quantities, can exert health benefits by preventing or reducing the severity of enteric pathogen infection. The bacteria-epithelial crosstalk between probiotic bacteria and gut epithelium suggests a specific mechanism by which probiotic bacteria can prevent infection by wide variety of enteric pathogens. We are identifying nutrients that enhance colonization by probiotic bacteria that could potentially benefit the millions of children affected by pathogen-induced diarrhea in developing countries.

When premature infants are born, their aseptic guts are rapidly colonized by microbes from the environment. If their gut is not sufficiently mature, the rapid microbial colonization leads to inappropriate excessive inflammation. Without control of the innate immune response that comes with maturity, the tissue develops an inflammatory disease called necrotizing enterocolitis. The lack of suitable model system limits our ability to study the etiology of this inflammatory disease of the premature infant gut.

We have developed a number of human and animal models during the past five years to study bacterial epithelial crosstalk that is vital for the wellbeing of all mammals. Using various cellular, molecular, genetic and proteomic approaches, mechanisms of bacteria-epithelial communication are investigated to identify unique interactions between the host intestinal mucosa and bacteria, including mutualistic symbionts, pathogens and probiotics.

BIBLIOGRAPHY

1. Chandrasena, G, I Sunitha, C Lau, NN Nanthakumar, SJ Henning. (1992) Expression of sucrase-isomaltase mRNA along the crypt villus axis in the rat small intestine. Cell. Molec. Biol. 38: 243–254.

2. Inui, Y, AML Hausman, NN Nanthakumar, SJ Henning, NO Davidson. (1992) Apolipoprotein B messenger RNA editing in rat liver: Developmental and hormonal modulation is divergent from apolipoprotein A-IV gene expression despite increased hepatic lipogenesis. J. Lipid Res. 33: 1843–1856.

3. Nanthakumar, NN, SJ Henning. (1993) Ontogeny of sucrase-isomaltase gene expression in rat small intestine: Responsiveness to glucocorticoids. Am. J. Physiol. 264: G306–G311.

4. Nanthakumar, NN, SJ Henning. (1994) Differentiating Glucocorticoid-Induced Maturation From Normal Development Using 5-Bromo-2'-Deoxyuridine (BUdR). Am. J. Physiol. 265: G216–G221.

5. Henning, SJ, NN Nanthakumar. (1994) Development of intestinal disaccharidases: A plurality of mechanisms. In: Mammalian Brush Border Membrane Proteins II., Ed: M. J. Lenze, H. Y. Naim and R. J. Grand: Georg Thieme Verlag, Stuttgart: page 243-249.

6. Lu, KP, NN Nanthakumar, JS Dayton, AR Means. (1995) Calcium and Calmodulin regulation of the nuclear division cycle of Aspergillus nidulans. In: Advances in Molecular and Cellular Biology., Ed: M. Wittaker: JAI Press Inc., Connecticut: Vol. 13; page 89-136.

7. Nanthakumar, NN, JS Dayton, AR Means. (1996) Role of Ca++/Calmodulin binding proteins in Aspergillus nidulans cell cycle regulation In: Progress in Cell Cycle Research. Vol.2, Ed: L. Meijer: Plenum, NY.

8. Dayton, JS, M Sumi, NN Nanthakumar, AR Means. (1997) Expression of constitutively active Ca++/Calmodulin dependent protein kinase in Aspergillus nidulans spores prevents germination and entry into the cell cycle. J. Biol. Chem. 272: 3223-3230.

9. Oesterreicher, TJ, NN Nanthakumar, JH Winston, SJ Henning. (1998) Cloning of rat trehalase cDNA and studies of the influence of glucocorticods on the ontogenic expression of trehalase mRNA in the small intestine. Am. J. Physiol. 274: R1220–R1227.

10. Dai D, NN Nanthakumar, DS Newburg, WA Walker. (2000) The role of oligosacharides and glycoconjugates in intestinal host defense. J. Pediatr. Gastr. Nutr. 30: S23-S33.

11. Nanthakumar NN, RD Fusunyan, IR Sanderson, WA Walker (2000) Endotoxin interaction with the developing human intestine: Pathophysiologic basis for necrotizing enterocolitis. Proc Natl Acad Sci., 97: 6043-6048.

12. Beck PL, R Xavier, N Lu, NN Nanthakumar, M Dinauer, Dk Podolsky, B Seed (2000) Mechanisms of NSAID-induced gastrointestinal injury defined using mutant mice. Gastroenterology 119:699-705

13. Fusunyan R, NN Nanthakumar, Baldeon, ME, Walker WA. (2001) Evidence for an innate immune response in the immature intestine: Toll-like receptors on fetal enterocytes. Pediatric Research 49:589-593

14. Nanthakumar NN. (2001) The Regulation of functional development of the small intestine. In: Gastrointestinal functions, Ed: E. Delvin and MJ Lentze. Nestlé Nutrition Workshop Series, Vol 46, Nestlé Ltd., Vevey/Lippincott Williams & Wilkins, Philadelphia: pp 39-58.

15. Dai D, NN Nanthakumar, T Savidge, DS Newburg, WA Walker. (2002) Tissue specific developmental regulation and cortisone induction of glycosyltransferase in the developing mouse intestine. I. alpha 2,6-sialytransferase. Am. J. Physiol. 282: G480–G490.

16. Nanthakumar NN, D Dai, DS Newburg, WA Walker. (2003) The induction of glycosyltransferases by colonizaing bacteria in germ free animal. The FASEB J.: G480–90.

17. Nanthakumar NN, CE Klopcic, I Fernandez, and Walker WA. (2003) Normal and glucocorticoid induced development of the human jejunal and ileal xenografts. Am. J. Physiol, 285: R162-70.

18. Nanthakumar N, Walker WA. (2003) Human intestinal development and maturation. In The small intestine Ed: MN Marsh and EMM Quiqley, Academic Press. Pp 1-24.

19. Nanthakumar N, Walker WA. (2004) The role of Bacteria in the Development of Intestinal Protective Function. In: Allergic Diseases and the Environment, Ed: W. A. Walker and E. Isolauri. Nestlé Nutrition Workshop Series, Vol 53, Nestlé Ltd., Vevey/Lippincott Williams & Wilkins, Philadelphia: In Press.

20. Nanthakumar NN, D Dai, D Meng, N. Chaudry, DS Newburg, WA Walker. (2005) Regulation of Intestinal Ontogeny: Effect of glucocorticoids and luminal microbes on Galactosyltransferase and Trehalase induction in mice. Glycobiology, 15(3):221-232.

21. Nanthakumar NN, C Young, JS Ko, D Meng, J Chen, T Buie, W.A Walker. (2005) Glucocorticoid responsiveness in the developing human intestine: A possible role in the prevention of necrotizing enterocolitis. Am. J. Physiol.; 288(1):G85-92.

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Updated 1/22/2007