Pawan Kumar, BVSc, PhD

Pawan Kumar Assistant Professor

Department of Microbiology and Immunology
Ph.D., University of Southampton, UK, 2009

E-mail:
Office:

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


Research


Mucosal Immunology

The major focus of my laboratory is to understand how immune cell, microbiota and epithelial cell cross-talk influences intestinal and extra intestinal mucosal host defense.

Our lab focuses on the following area of research

Project 1: IL-17A and mucosal host defense: IL-17A, derived from Th17 cells, is a pro-inflammatory cytokine implicated in autoimmune and metabolic disorders. However, IL-17A also has beneficial effects in the gut. This differential role of IL-17A in gastrointestinal homeostasis versus systemic autoimmunity remains unclear. Our data supports the concept that Th17 cells are 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 cell-specific IL-17 receptor knockout mouse strains, our laboratory is actively involved in understanding the underlying cellular and molecular mechanisms involved in the regulation of intestinal homeostasis, the microbiome as well as systemic metabolic and autoimmune disorders.

Project 2: IL-22 and mucosal host defense. IL-22, derived from type 3 innate lymphoid cells (ILC3) and Th17 cells, plays an important role in intestinal and extra-intestinal host defense. Mice deficient in IL-22 or its receptor, IL-22Ra1, are highly susceptible to colitis and metabolic disorders. The pleiotropic effects of IL-22 coupled with the diverse array of cell types (gut epithelial, hepatocytes and adipocytes) that express IL-22Ra1 have made it difficult to interpret prior results obtained with germ-line knockout mice models. How IL-22 interacts with specific intestinal (Paneth, goblet and absorptive enterocytes) and extra-intestinal (hepatocytes and adipocytes) cell types and whether molecular synergy exists among these organs remains unclear. Our lab is actively involved in understanding the mechanisms of IL-22-mediated protective and inflammatory roles in IBD and systemic metabolic disorders.

Project 3: Regulation of differentiation pathways of Th17 cells: Our lab studies the molecular pathways regulating immune cell (especially Th17 cell) differentiation. Murine Th17 cell differentiation is influenced by various cytokines including IL-6, TGFb, IL-23 and IL-1b.  RORγt and Aryl hydrocarbon receptor (AhR) have been shown to regulate Th17 cells. Th17 cells still differentiate in the absence of AhR.  We found that nuclear factor (erythroid-derived 2)-like 2 (Nrf2) selectively regulates IL-17A and IL-22 responses in CD4+ T cells. Our lab is actively involved in screening additional pathways that regulate Th17 cell differentiation.

Project 4: Microbiota regulation of autoimmune disorder: Multiple Sclerosis (MS) patients have dysregulated immune responses (IL-17A, GM-CSF and IFNg) as well as alterations in their gut microbiota (increased prevalence of Akkermansia muciniphila) compared to healthy adults. Although, the gut microbiota composition of MS patients has been thoroughly studied, the impact of their altered microbiota and microbiota-derived metabolites on systemic autoimmunity remains unclear. In collaboration with physician scientists, our lab is actively investigating how the microbiota and their metabolites regulate inflammatory responses during different stages of MS. Using mouse model of MS, we are actively investigating whether specific gut bacteria including A. muciniphila confers a protective or damaging role in MS/EAE.
 

Publications

Selected 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. Gaudino S, Beaupre M, Lin X, Joshi P, Rathi S, McLaughin P, Mehta N, Kempen C, Eskiocak O, Yueh B, Blumberg R, van der Velden A.W.M, Shroyer K.R, Bialkowska A.B, Beyaz S and Kumar  P. IL-22 receptor signaling in Paneth cells is critical for their maturation, microbiota colonization, Th17-related immune responses and anti-Salmonella immunity. Accepted Mucosal Immunology.
  2. Huang XYang W, Yao S, Bilotta A, Lu Y, Zhou ZKumar P, Dann M. S and Cong Y. IL-21 Promotes Intestinal Memory IgA Responses. Accepted Journal of Immunology.
  3. Castillo-dela Cruz P., Wanek A.G., Kumar P., Chen K., An X., Elsegeiny W., Horne W., Fitch A., Methe., B, Burr A., Gopalkrishna K., Canna S., Hand T.W. and Kolls J.K. Intestinal IL-17R signaling constrains IL-18 driven liver inflammation by the regulation of microbiome-derived products. Cell Report, 2019 Nov 19;29(8):2270-2283. [PMID: 31747600].
  4. Kumar P., Rajasekaran K., Nanbakhsh A., Gorski J., Thakar M.S. and Malarkannan S IL-27 promotes NK cell effector functions via Maf-Nrf2 pathway during influenza infection. Scientific Report, 2019 Mar 21;9(1):4984. doi: 10.1038/s41598-019-41478-6. [PMID: 30899058].
  5. 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 Jul 1;197(1):97-107. [PMID: 27217583].
  6. 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 March 44 (3); 659–671. [PMID: 26982366].
  7. 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 Sep 23;111(38):13942-7. [PMID: 25201978].
  8. 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 Nov;14(11):1127-36. [PMID: 24036998].
  9. 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 Jan;6(1):69-82. [PMID: 22739232].
  10. 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 Sep 9;286(36):31213-24. [PMID: 21771792].
  11. 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 (*Co-first author)

Lab Members

Postdoctoral Fellows

Ankita Singh, PhD
Tej Bahadur, PhD

Graduate Students

Stephen Gaudino
Xun Lin
Hoi Tong Wong
Cody Kempen

Research Technician

Suzanne Tawch