N. Nanda Nanthakumar, PhD
2003PhD, Cell, Molecular and Developmental BiologyUniversity of Houston
1995BS, Zoology (Honors) and BotanyUniversity of PeradeniyaSri Lanka
- Postnatal Development of the Intestine: Role of glucocorticoids and growth factors in intestinal stem cell biology, epithelial differentiation and restitution after injury.
- Glycosylation and Host Genetics: Consequence in microbial succession and establishment of bacteria, viruses, archaea, phage and fungi ecosystem in the gut microbiome.
- Microbiome: Effect on intestinal physiology, innate immune maturation and inflammation (necrotizing enterocolitis, Crohn’s disease, type-1 diabetes, and obesity), enteric infection, probiotic microbes and prebiotics dietary supplement, in health and diseases.
- One Health and Dietary Supplementation: Impact on diarrheal diseases, development of the mucosal immunity and the onset of inflammatory diseases.
Current Research and Objectives
The overall objective of the Mucosal Immunology and Gastrointestinal Pathophysiology Laboratory is to elucidate molecular mechanisms by which mutualistic host-microbial interaction regulates intestinal homeostasis, susceptibility to age-specific infection, digestive physiology, and disease susceptibility.
A unique and dynamic microbial ecosystem of the digestive tract is acquired after birth. Its composition is influenced by the mucosal phenotype dictated by the host genetics, as well as the extrinsic factors, such as diet and environmental exposure, and intrinsic factors, such as circulating hormones like glucocorticoids. Mutualism between the host and gut microbiota are critical for optimum nutritional acquisition, postnatal growth, age-appropriate mucosal immune maturation that prevents pathogen infection and promote metabolic and immune homeostasis.
The overall objectives are to identify and characterize the molecular mechanisms by which digestive/absorptive and mucosal immune functions are regulated by distinct microbial communities and how dietary prebiotic supplements, probiotic and prebiotic therapy and circulating hormones modulate the rate of colonization and the composition of the gut microbiota.
Specific goals are to investigate how specific component of the gut microbes promote:
- development of the mucosal immune system;
- establishment of a beneficial microbial community with probiotic bacteria;
- postnatal maturation of mucosal glycosylation;
- resistance to age-specific bacterial and viral infection;
- age-appropriated inflammatory response to inflammation and mucosal injury;
- metabolic homeostasis and neurobehavioral development.
The studies will use molecular, cellular, genetic, microbiology and systems biology approaches using in vitro and small and large animal in vivo models.
2013 – PresentAssociate ProfessorMucosal Immunology, Microbiome, and Inflammatory DiseasesVirginia-Maryland College of Veterinary MedicineVirginia TechBlacksburg, VA
2013 – PresentAssociate ProfessorMucosal Immunology, Microbiome, and Inflammatory DiseasesTranslational Biology, Medicine, and Health ProgramVirginia TechBlacksburg, VA
2005 – 2012Assistant ProfessorPediatricsHarvard Medical SchoolBoston, MA
1998 – 2005InstructorPediatricsHarvard Medical SchoolBoston, MA
1998 – 2005Assistant BiologistMassachusetts General HospitalBoston, MA
1993 – 1998Research AssociateDuke University Medical CenterDurham, NC
- American Physiological Society
- American Gastroenterological Association
- American Society for Nutrition
- American Society for Mucosal Immunologist American Society for Nutrition
- American Association for the Advancement of Science
- Nanthakumar NN, Meng D, Newburg DS. Glucocorticoids and microbiota regulate ontogeny of intestinal fucosyltransferase 2 requisite for gut homeostasis. Glycobiology, 23:1131-41, 2013.
- Ganguli K, Meng D, Rautava S, Lu L, Walker WA, Nanthakumar NN. Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation. Am J Physiol Gastrointest Liver Physiol., 304:G132-41, 2013.
- Nanthakumar NN, Meng D, Goldstein A, Zhu W, Lu L, Uauy R, Llanos A, Claud E, Walker WA. The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: An immature innate immune response. PLoS One, 2011, 6(3): e17776.
- Long KZ, Rosado JL, Santos JI, Estrada-Garcia T, Zhu W, Haas M, Mamun AL, DuPont HL, Nanthakumar NN. Vitamin A Supplementation Modifies the Association between Mucosal Innate and Adaptive Immune Responses and Resolution of Enteric Pathogen Infections. Am. J Clini. Nutri. 93:578-585, 2011.
- Long KZ, Rosado JL, Santos JI, Haas M, Mamun AN, DuPont HL, Nanthakumar NN, and Teresa Estrada-Garcia. Associations between mucosal innate and adaptive immune responses and resolution of diarrheal pathogen infections. Infection and Immunity. 78:1221-8, 2010.
- Beck P, Ihara E, Mizoguchi E, Meng D, Nanthakumar NN, Seed B, Podolsky DK, Xavier RJ. Targeted Disruption of Fucosyltransferase VII Attenuates the Susceptibility of Trefoil Factor-3 Deficient Mice to Intestinal Inflammation. Am J Physiol Gastrointest Liver Physiol., 299:G43-53, 2010.
- Chen X, Katchar K, Goldsmith JD, Nanthakumar N, Cheknis A, Gerding DN, Kelly CP. A Mouse Model of Clostridium difficile-Associated Disease. Gastroenterology 135:1984-92, 2008.
- Meng D, Newburg DS, Young C, Baker A, Tonkonogy SL, Sartor RB, Walker WA, NN Nanthakumar. Bacterial symbionts induce a FUT2-dependent fucosylated niche on colonic epithelium via ERK and JNK signaling. Am J Physiol Gastrointest Liver Physiol., 293: G780-7, 2007.
- Broekaert IJ, Nanthakumar NN, Walker WA. Secreted probiotic factors ameliorate enteropathogenic infection in zinc-deficient human Caco-2 and T84 cell lines. Pediatr Res., 62:139-44, 2007.
- Long KZ, Estrada-Garcia T, Rosado JL, Santos JI, Haas M, Firestone M, Bhagwat J, Young C, DuPont HL, Hertzmark E, Nanthakumar NN. The Effect of Vitamin A Supplementation on the Intestinal Immune Response in Mexican Children Is Modified by Pathogen Infections and Diarrhea. J Nutr.136:1365-70, 2006.
- Nanthakumar NN, D. Dai, D. Meng, N. Chaudry, DS. Newburg, WA Walker. Regulation of Intestinal Ontogeny: Effect of Glucocorticoids and Luminal Microbes on Galactosyltransferase and Trehalase Induction in Mice. Glycobiology, 15:221-232, 2005.
- Nanthakumar NN, Dai D, Newburg DS, Walker WA. The role of indigenous microflora in the development of murine intestinal fucosyl- and sialyltransferases. FASEB J. 17:44-6, 2003.
- Nanthakumar NN, Fusunyan RD, Sanderson I, Walker WA. Inflammation in the developing human intestine: A possible pathophysiologic contribution to necrotizing enterocolitis. Proc Natl Acad Sci U S A., 97:6043-8, 2000.
- Nanthakumar NN, Dayton JS, Means AR. Role of Ca++/calmodulin binding proteins in Aspergillus nidulans cell cycle regulation. Prog Cell Cycle Res. 2:217-28, 1996.
- Nanthakumar NN, Henning SJ. Distinguishing normal and glucocorticoid-induced maturation of intestine using bromodeoxyuridine. Am J Physiol. 268:G139-45, 1995.