Matam Vijay-Kumar, Ph.D.
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Professor Director, The University of Toledo-Microbiome Consortium (UT-MiCo) Phone: 419.383.4130 Email: MatamVijay.Kumar@UToledo.Edu |
Education:
Ph.D., Biochemistry, Central Food Technological Research Institute, Mysore, India 2002.
Research Interests:
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.
Gut Microbiota, Host Innate Immunity in Gastrointestinal infections
The dynamics between innate immunity, gut microbiota and gastrointestinal pathogens
frame many of my research questions. The co-ordination and fine tuning between accessory
immune cells (e.g. epithelia) and professional immune cells (e.g. neutrophils and
macrophages) helps not only in gut microbiotal homeostasis but also helps in eradication
of perturbing pathogens in the gut. These cells express specific 'pattern recognition
receptors' (PRRs), which broadly sense specific microbial ligands and evoke innate
immune response and helps in gut homeostsis. In addition, we demonstrate that microbial
products (i.e.viral RNA, flagellin) which potently activate their cognate TLR activation and broadly
protect against enteropathogens and viruses.
Neutrophil Extracellular Traps: Safety Nets for Gut Microbiota and Pathogens
Neutrophils are the most abundant circulating white blood cells and first responders
to infection, inflammation and injury. These professional phagocytes are equipped
with diverse antimicrobial proteins/peptides which can effectively kill diverse microorganisms.
Recently, it has been shown that neutrophils also display another weapon in their
armory i.e. neutrophil extracellular traps (NETs). NETs generation is initiated by the activity
of an enzyme peptidyl-argininine deiminase 4 (PAD4), which helps in the rapid chromatin
decondensation and fecilitates expelling neutrophil DNA in the form of cob-web like
structures called as NETs. Our laboratory is actively pursuing the role of NETs in
gastrointestinal physiology, gut microbiota homeostasis and gastrointestinal infections
by employing PAD4 deficient mice.
For a complete list of Dr. Kumar's publications please click here.
Selected Publications:
Xiao X, Saha P, Yeoh BS, Hipp JA, Singh V, Vijay-Kumar M. Myeloperoxidase deficiency attenuates systemic and dietary iron-induced adverse effects. J Nutr Biochem. 2018 Dec;62:28-34. doi: 10.1016/j.jnutbio.2018.08.003. Epub 2018 Aug 21.PubMed PMID: 30218980; PubMed Central PMCID: PMC6263781.
Singh V, Yeoh BS, Chassaing B, Xiao X, Saha P, Aguilera Olvera R, Lapek JD Jr, Zhang L, Wang WB, Hao S, Flythe MD, Gonzalez DJ, Cani PD, Conejo-Garcia JR, Xiong N, Kennett MJ, Joe B, Patterson AD, Gewirtz AT, Vijay-Kumar M. Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer. Cell. 2018 Oct 18;175(3):679-694.e22. doi: 10.1016/j.cell.2018.09.004. PubMed PMID: 30340040; PubMed Central PMCID: PMC6232850.
Saha P, Xiao X, Yeoh BS, Chen Q, Katkere B, Kirimanjeswara GS, Vijay-Kumar M. The bacterial siderophore enterobactin confers survival advantage to Salmonella in macrophages. Gut Microbes. 2018 Nov 18:1-12. doi:10.1080/19490976.2018.1546519. [Epub ahead of print] PubMed PMID: 30449241.
*Singh V, Yeoh BS, Chassaing B, Xiao X, Saha P, Aguilera Olvera R, Lapek JD Jr, Zhang L, Wang WB, Hao S, Flythe MD, Gonzalez DJ, Cani PD, Conejo-Garcia JR, Xiong N, Kennett MJ, Joe B, Patterson AD, Gewirtz AT, Vijay-Kumar M. Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer. Cell 2018 PMID:30340040 PMCID:PMC6232850
(click title to view article) *Article highlighted by commentary published in Cell Metabolism: https://www.cell.com/cell-metabolism/pdf/S1550-4131(18)30641-7.pdf
Chakraborty S, Galla S, Cheng X, Yeo JY, Mell B, Singh V, Yeoh B, Saha P, Mathew AV, Vijay-Kumar M, Joe B. Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension.
Cell reports. 2018 PMCID:PMC6232850 (click title to view article)
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
Nov 14;346(6211):861-5.
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.