Matam Vijay-Kumar (Vijay), PhD
110 Chandlee Lab
University Park PA 16802
Ph.D., Biochemistry, Central Food Technological Research Institute, Mysore, India 2002.
1. Host Metabolic Adaptations to Inflammation
Inflammation is a host protective response to mediate clearance of invading pathogens, irritants, or damaged cells. To fuel the inflammatory process, our body undergo metabolic adaptation to allow greater expenditure of energy. However, as in the case of low-grade chronic inflammation, the continuous metabolic burden inadvertently potentiates the development type 2 diabetes and obesity and leading to symptoms of metabolic syndrome. Hence, the primary vein of my research pertains to the interplay between intestinal inflammation and metabolic disorders. My research demonstrates that Toll-like receptor 5 (TLR5)-deficient mice prone to develop spontaneous gut inflammation. To cope up with gut inflammation, these mice adapt alternate metabolic pathways which protect against inflammation but culminates into metabolic diseases. We believe that development of metabolic syndrome in TLR5 deficient mice can be viewed as metabolic adaptation to inflammation.
2. Innate Immunity-Gut Microbiotal Interactions in Metabolic Diseases
The dynamics between innate immunity and gut microbiota frame many of my research questions. A large body of my work focuses on understanding the mechanisms by which the innate immune response helps in the gut microbiotal homeostasis. Specifically, we demonstrate that microbial products (i.e.viral RNA, flagellin) which potently activate their cognate TLR activation and broadly protect against insults such as chemicals, viruses and radiation.
3. Lipocalin 2 - mediated Iron Homeostasis in Inflammation
My research has shown that Lipocalin 2 (Lcn2), a protein elevated during the inflammatory response, can serve as a robust biomarker for intestinal inflammation. More recently, my studies have grown to encompass exploration on the role of Lcn2 in iron homeostasis during inflammation. During this endeavor, I demonstrate that Lcn2 facilitates the hypoferremia of inflammation and also protects against iron-induced toxicity. Loss of Lcn2 disrupts iron homeostasis with adverse consequences not only to the host, but also leads to gut microbiotal dysbiosis that aggravate the host’s susceptibility to colitis.
Xiao X, Yeoh BS, Saha P, Olvera RA, Singh V, Vijay-Kumar M. Lipocalin 2 alleviates iron toxicity by facilitating hypoferremia of inflammation and limiting catalytic iron generation. Biometals 2016 Mar 23.
Yeoh BS, Aguilera Olvera R, Singh V, Xiao X, Kennett MJ, Joe B, Lambert JD, Vijay-Kumar M. Epigallocatechin-3-Gallate Inhibition of Myeloperoxidase and Its Counter-Regulation by Dietary Iron and Lipocalin 2 in Murine Model of Gut Inflammation. Am J Pathol. 2016 Apr;186(4):912-26.
Singh V, Kumar M, San Yeoh B, Xiao X, Saha P, Kennett MJ, Vijay-Kumar M. Inhibition of Interleukin-10 Signaling Induces Microbiota-dependent Chronic Colitis in Apolipoprotein E Deficient Mice. Inflamm Bowel Dis. 2016 Apr;22(4):841-52.
Singh V, Chassaing B, Zhang L, San Yeoh B, Xiao X, Kumar M, Baker MT, Cai J, Walker R, Borkowski K, Harvatine KJ, Singh N, Shearer GC, Ntambi JM, Joe B, Patterson AD, Gewirtz AT, Vijay-Kumar M. Microbiota-Dependent Hepatic Lipogenesis Mediated by Stearoyl CoA Desaturase 1 (SCD1) Promotes Metabolic Syndrome in TLR5-Deficient Mice. Cell Metab 2015 Dec 1;22(6):983-96.
Singh V, Yeoh BS, Carvalho F, Gewirtz AT, Vijay-Kumar M. Proneness of TLR5 deficient mice to develop colitis is microbiota dependent. Gut Microbes 2015 Jul 4;6(4):279-83.
Singh V, Yeoh BS, Xiao X, Kumar M, Bachman M, Borregaard N, Joe B, Vijay-Kumar M. Interplay between enterobactin, myeloperoxidase and lipocalin 2 regulates E. coli survival in the inflamed gut. Nat Commun. 2015 May 12;6:7113.
Zhang B, Chassaing B, Shi Z, Uchiyama R, Zhang Z, Denning TL, Crawford SE, Pruijssers AJ, Iskarpatyoti JA, Estes MK, Dermody TS, Ouyang W, Williams IR, Vijay-Kumar M, Gewirtz AT. Viral infection. Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18. Science 2014
Srinivasan G, Aitken JD, Zhang B, Carvalho FA, Chassaing B, Shashidharamurthy R, Borregaard N, Jones DP, Gewirtz AT, Vijay-Kumar M. Lipocalin 2 deficiency dysregulates iron homeostasis and exacerbates endotoxin-induced sepsis. J Immunol. 2012 Aug 15;189(4):1911-9.
Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 2010 Apr 9;328(5975):228-31.
Vijay-Kumar M, Sanders CJ, Taylor RT, Kumar A, Aitken JD, Sitaraman SV, Neish AS, Uematsu S, Akira S, Williams IR, Gewirtz AT. Deletion of TLR5 results in spontaneous colitis in mice. J Clin Invest. 2007 Dec;117(12):3909-21.