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Pawan Kumar, BVSc, PhD

Pawan Kumar Assistant Professor of Molecular Genetics and Microbiology

Ph.D., University of Southampton, UK, 2009

270 Life Sciences building
Stony Brook University,
Stony Brook, NY 11794-5120

E-mail:
Office:

pawan.kumar@stonybrook.edu
(631) 632-4242

 

Publications

Research

The host immune response to commensal bacteria has been the subject of intense research to determine whether a beneficial regulatory response can be exploited therapeutically. Th17 and innate lymphoid cells (ILC)3-derived IL-17A and IL-22 are promising targets that have great potential in reducing intestinal injury and preserving the epithelial barrier. Our lab and others have shown that IL-17A and IL-22 are important for regulating commensal microbiota colonization. Moreover, our group was the first to describe IL-17RA signaling in intestinal epithelium and its importance in commensal colonization.

The aberrant immune response to commensal bacteria has been thought to play a critical role in the development of several diseases including inflammatory bowel diseases (IBD) and autoimmune disorders. The underlying mechanisms leading to IBD are poorly understood. IBD patients have an increase in Th17 cells that produce IL-17A and IL-17F within the disease lesion, and these elevated immune responses has been thought to play a pathological role in IBD. However, a recent clinical trial with a neutralizing IL-17A monoclonal antibody in IBD patients was not protective, and was associated with increased adverse events, suggesting IL-17A immune responses are beneficial in the gut. In contrast, IL-17A has been shown to play a pathological role in certain autoimmune disorders including multiple sclerosis (MS). The 25.3% disease concordance rate in monozygotic twins strongly suggests that environmental factors, possibly gut microbiota, significantly contribute to MS pathogenesis. Indeed, microbiota analysis in MS patients is an area of active exploration, and it has been reported that MS patients have alterations in the gut microbiota as compared to healthy adults. Despite extensive advancement of MS research, the etiology of the autoimmunity in MS is poorly understood, and it is still unclear whether disease initiates in the CNS or in the periphery. Thus, there remains a critical need to understand the mechanisms leading to the development of MS.

The major focus of my laboratory is to understand how IL-17A and IL-22 regulates intestinal and extra intestinal host defense, with the ultimate goals of revealing effective approaches to treat IBD and autoimmune inflammation. 

Our lab focuses on following area of research

Project 1: IL-17A and mucosal host defense: Several recent studies suggested that enteric IL-17A responses have a beneficial effect in the gut. However, the mechanisms of protective role of IL-17A in the gut are poorly understood. In contrast, IL-17A has been shown to play a pathological role in certain autoimmune disorders and psoriasis. Our data supports the concept that Th17 cells is beneficial in controlling commensal dysbiosis in the gut but may be harmful if dysregulated or elicited against auto-antigens. Taking advantage of multiple intestinal epithelial cells-specific IL-17R knockout mouse strains, our laboratory is actively involved in understanding the underlying cellular and molecular mechanisms involved in the regulation of intestinal inflammation, the microbiome, as well as autoimmune inflammation.

Project 2: IL-22 and intestinal host defense. While IL-22 is also beneficial in regulating commensal colonization, the exact mechanisms, and whether there is molecular synergy between IL-17A and IL-22 signaling pathways to regulate commensal colonization remains unclear. Using gut epithelial cells-specific IL-22ra1 knockout mice as well as primary intestinal organoid culture, our laboratory investigates the IL-22-dependent host defense pathways in the gut.

Project 3: Metabolic reprogramming in immune cells: Naïve T cells exist in a quiescent stage and rely on mitochondria-dependent oxidative phosphorylation (OXPHOS) as the energy source for basic metabolic functions. In contrast, activated T cells mainly rely on aerobic glycolysis pathways to fuel increased demand of bioenergetic and biosynthetic activities. Our lab studies the molecular pathways regulating the metabolic functions of immune cells.

 


Select
Publications

  1. McAleer JP, Nguyen N, Chen K, Kumar P, Ricks DM, Binnie M, Armentrout RA, Pociask D, Hein A, Yu W, Vikram A, Bibby K, Umesaki Y, Rivera A, Sheppard D, Ouyang W, Hooper LV and Kolls JK. Pulmonary Th17 anti-fungal immunity is regulated by the gut microbiome. Journal of Immunology, 2016, 97(1): 97-107.
  2. Kumar P., Monin L., Castillo P., Elsegeiny W., Horne W, Eddens T., Vikram A.,  Good M., Schoenborn A., Bibby B., Montelaro R., Metzger DW., Gulati A. and Kolls J.K. Intestinal IL-17 Receptor Signaling Mediates Reciprocal Control of the Gut Microbiota and Autoimmune Inflammation. Immunity. 2016, 44 (3); 659–671. [PMID: 26982366].
  3. Shih V.F., Cox J., Kljavin N., Dengler HS., Reichelt M., Kumar P., Rangell L., Kolls J.K., Diehl L, Ouyang W. and Ghilardi N. Homeostatic IL-23R signaling limits TH17 response through IL-22-mediated containment of commensal microbiota. Proc Natl Acad Sci U S A. 2014, 23;111(38):13942-7. [PMID: 25201978].
  4. Rajasekaran K., Kumar P., Schuldt KM., Peterson E.J., Vanhaesebroeck B., Dixit V., Thakkar M.S. and Malarkannan S. Signaling by Fyn-ADAP via the Carma1–Bcl-10–MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells. Nature Immunology.  2013,14(11):1127-36. [PMID: 24036998].
  5. Kumar P., Thakar M.S., Ouyang W. and Malarkannan S. IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection.  Mucosal Immunology. 2013, 6(1):69-82. [PMID: 22739232]. 
  6. Kumar P., Bartoszek A.E., Moran T.M., Gorski J., Navidad J.F., Bhattacharyya S., Thakkar M.S. and Malarkannan S. High-throughput detection method for influenza virus. Journal of Visualized Experiment. 2012, (60). pii: 3623. [PMID: 22331038].
  7. Rajasekaran K., Chu H., Kumar P., Xiao Y., Tinguely M., Samarakoon A., Kim T.W., Li X, Thakkar M.S., Zhang J. and Malarkannan S. Transforming growth factor-beta-activated kinase 1 regulates natural killer cell-mediated cytotoxicity and cytokine production. Journal of Biological Chemistry. 2011, 286(36):31213-24. [PMID: 21771792].
  8. Guo H*., Kumar P*., Moran T.M., Garcia-Sastre A., Zhou Y. and Malarkannan S. The functional impairment of natural killer cells during influenza virus infection. Immunology and Cell Biology. 2009, 87(8):579-89. [PMID: 19721456]. Outstanding observation (*Co-first author
  9. Majtan J*., Kumar P*., Majtan T., Walls A.F. and Klaudiny J. Effect of honey and its major royal jelly protein 1 on cytokine and MMP-9 mRNA transcripts in human keratinocytes. Experimental Dermatology. 2010,19(8):e73-9. [PMID: 19845754] (*Co-first author)
  10. Kumar P., Williams J.N., Durkin K.L., Heckels J.E., Friedmann P.S., Healy E, Christodoulides M. Neuropeptide alpha-MSH exerts pro-inflammatory effects on Neisseria meningitidis infection in vitro. Inflammation Research. 2010, 59(2):105-13. [PMID: 19685205].
  11. Pickard C., Louafi F., McGuire C., Lowings K., Kumar P., Cooper H., Dearman R.J, Cumberbatch M., Kimber I., Healy E. and Friedmann P.S. The cutaneous biochemical redox barrier: a component of the innate immune defences against sensitisation by highly reactive environmental xenobiotics. Journal of Immunology.  2009,183(11):7576-84. [PMID: 19890059].
  12. Majtan J., Kumar P., Koller J., Dragúnová J. and Gabriz J. Induction of metalloproteinase 9 secretion from human keratinocytes by pleuran (beta-glucan from Pleurotus ostreatus). Z. Naturforsch. C. 2009, 64 (7-8):597-600. [PMID: 19791514]. 
 

Review, Commentaries and Book Chapters

  1. Kumar P., Chen K. and Kolls J.K. Th17 cell based vaccines in mucosal immunity. Current Opinion in Immunology. 2013, 25(3):373-80. [PMID: 23669353].
  2. Kumar P. and Kolls J.K. Act1-hsp90 heats up TH17 inflammation. Nature Immunology. 2013 Jan;14(1):16-17. [PMID: 23238753].
  3. Kumar P., Rajasekaran K., Palmer J.M., Thakkar M.S. and Malarkannan S. IL-22: An Evolutionary Missing-Link Authenticating the Role of the Immune System in Tissue Regeneration. Journal of Cancer. 2013;4(1):57-65. [PMID: 23386905].
  4. Malarkannan S., Awasthi A., Rajasekaran K., Kumar P., Schuldt K.M., Bartoszek A., Manoharan N., Goldner N.K., Umhoefer C.M. and Thakkar MS. IQGAP1: a regulator of intracellular space time relativity. Journal of Immunology. 2012,1;188(5):2057-63. [PMID: 22345702].
  5. Guo H., Kumar P. and Malarkannan S. Evasion of Natural Killer cells by influenza virus. Journal of Leukocytes Biology. 2011; 89: 189-194. [PMID: 20682623].

Lab Members

Postdoctoral Fellow

Anirban Banerjee, PhD

Graduate Student

Michael Beaupre

Research Support Specialist

Huakang Huang, PhD