Vishwa Deep Dixit, DVM, Ph.D.
Head, Immunobiology Laboratory
1994- Doctor of Veterinary Medicine, CCS Haryana Agricultural University- Hisar, India
1996 - Masters of Veterinary Science, Animal Physiology, CCS Haryana Agricultural University- Hisar, India.
2000 - Ph.D, Physiology. University of Hannover, Institut Fuer Tierzucht, Mariensee, Germany and HAU-India.
2001 to 2005 - Post Doc Fellow - NIH.
This is a NIH funded laboratory with interests in the interactions between metabolic and immune systems that participate in origin of inflammation and immune dysfunction in aging and obesity.
The two major areas of interest of my laboratory are to (a) understand the mechanism of immune-senescence and (b) to determine the origin of metabolically driven inflammation. The long-term goal of my research is to help develop novel approaches to forestall or even reverse the aging of immune system and to regulate the aberrant immune cell activation as means to enhance healthspan. This Laboratory utilizes basic cellular and molecular tools, genetic manipulations including reporter and Cre/Lox mouse models to understand patho-physiology of obesity and aging.
IMMUNE-SENESCENCE: Diminished ability of the thymus to produce naive T cells with advancing age remains a fundamental and puzzling phenomenon for biology and to date, an intractable clinical condition which contributes to lower immune-surveillance in elderly persons. The current approaches for lifespan extension and to compress age-related morbidity often draws on the analogy of “one hoss shay”, a long-lasting fictitious carriage described by the poet Oliver Wendell Holmes which “went to pieces all at once, and nothing first – just as bubbles do when they burst” because all its high-quality parts were equally strong and destructed simultaneously. Importantly, aging of the thymus even in good health, precedes aging of several other organs. Our recent imaging data from the NIA funded CALERIE-II study demonstrates that by 45 years of age in metabolically healthy individuals, greater than 75% of thymic stromal cell microenvironment is dysfunctional and is transformed into adipose tissue. Therefore, in healthy middle-age people, when the thymus is transformed into adipose tissue mass, while the other organs are still functionally intact, poses a major biological impediment to “one hoss shay” compressed morbidity model of keeping all organs equally strong as we age. Therefore, the ability to prevent or reverse thymmic aging is one the long-term research goals of this laboratory as means to prolong healthy lifespan.
INFLAMMATION: It is established that the circulating and tissue levels of pro-inflamamtory cytokines are elevated in obesity and aging. The overall goal of our project is to identify the endogenous danger signals or “inducers”, that are recognized by specific immune “sensors” like the NLRP3 inflammasome, which regulates production of “mediators” of inflammation, such as IL-1ß and IL-18. The predicted findings have implications for understanding the obesity and age-associated co-morbidities and underlying immune cell dysfunction with direct translational relevance.
Post Doctoral Fellow
Research in this laboratory is supported by the National Institutes of Health (NIA-R01AG031797), NIDDK-R01DK090556) Pilot Awards from NIDDK funded NORC grant (1P20 RR02/1945) and the Coypu Foundation.
(selected from 53)
Dixit VD. (2013) Nlrp3 inflammasome activation in type 2 diabetes: is it clinically relevant? Diabetes 62: 22-24.
Dixit VD. (2013) Adipose Tissue Macrophages are Innate to the Immunological awareness of Adipose tissue. Diabetes (in press)
Grant RW, Dixit VD. (2013) Mechanisms of disease: inflammasome activation and the development of type 2 diabetes. Front Immunol. 2013;4:50. doi: 10.3389/fimmu.2013.00050
Kanneganti TD and Dixit VD. (2012). Immunological complications of obesity. Nat. Immunol.13, 707-712.
Dixit VD. (2012) Impact of immune-metabolic interactions on age-related thymic demise and T cell senescence. Semin. Immunol. Epub ahead of print Apr 28.
Youm YH, Kanneganti TD, Vandanmagsar B, Zhu X, Ravussin A, Adijiang A, Owen JS, Thomas MJ, Francis J, Parks JS and Dixit VD (2012) The NLRP3 Inflammasome Promotes Age-related Thymic Demise and Immunosenescence. Cell Reports 1: 56-68.
* Article selected for commentary in Nature Reviews Immunology 12: 154 March 2012.
* Article selected for Cell Reports Highlight
* Selected by Faculty 1000 as top 2% published article in the field (Evaluated by G. Pawelec)
Dixit VD (2012). Editorial: Lipids :fueling the fire in tuberculosis? J. Leukoc. Biol. Jun;91(6):843-4.
Youm YH, Ayinuer A, Vandanmagsar B, Burk D, Ravussin A, Dixit VD. (2011) Elimination of the NLRP3-ASC inflammasome protects against chronic obesity-induced pancreatic damage. Endocrinology, 152 (11): 4039-4045.
* Article selected for News and Views in November 2011 issue of Endocrinology (commentary by Marc Donath)
Vandanmagsar B, Youm YH, Ravussin A, Galgani J, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature. Med. 17(2): 179-188.
* Article selected for a Commentary in February issue of Nature Medicine (commentary by T Horng and G Hotamisligil)
* Article selected for a Commentary in May issue of Nature Immunology. (commentary by A Choi and K Nakahira)
* Article selected for a Commentary in May Issue of Circ. Res.
(commentary by Mori, Bezy and Ron Kahn)
* Article selected as research highlight in Cell Research (May 24, commentary by M Boni-Schnetzler and M Donath)
Dixit VD, Yang H, Sayeed KS, Stote KS, Rumpler WV, Baer DJ, Longo DL, Mattson MP, Taub DD.(2011)Controlled meal frequency without caloric restriction alters peripheral blood mononuclear cell cytokine production. J Inflamm (Lond). 2011 Mar 7;8:6.
* Designated as highly accessed article by PubMed Central
Yang H, Youm YH, Vandanmagsar B, Ravussin A, Gimble JM, Greenway F, Stephens JM, Mynatt R and Dixit VD. (2010) Obesity increases the production of pro-inflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: Implications for systemic inflammation and insulin-resistance. J. Immunol. 185: 1836-1845.
Dixit VD. (2010) Thymic fatness and approaches to enhance thymopoietic fitness in aging. Curr. Opin. Immunol. 22: 1-8.
Youm YH, Yang H, Amin R, Smith SR, Leff T and Dixit VD. (2010). Thiazolidinedione treatment and constitutive-PPARgamma activation induces ectopic adipogenesis and promotes age-related thymic involution. Aging Cell. 2010 Apr 1. [Epub ahead of print] PMID: 20374200
Yang H, Youm YH, Vandanmagsar B, Rood J, Kumar KG, Butler AA and Dixit VD. (2009). Obesity accelerates thymic aging. Blood. Oct 29;114(18):3803-3812. PMID: 19721009
Yang H, Youm YH and Dixit VD. (2009). Inhibition of Thymic Adipogenesis by Caloric Restriction is coupled with Reduction in Age-related Thymic Involution. J. Immunol. Sep 1;183(5):3040-52.
Yang H, Youm YH, Sun Y, Rim JS, Galban C, Vandanmagsar B, Dixit VD. (2009) Axin expression in thymic stromal cells contributes to age-related increase in thymic adiposity and associated with reduced thymopoiesis independently of ghrelin signaling. J. Leukoc Biol. 85: 928-938.
Youm YH, Yang H, Sun Y, Smith RG, Manley NR, Vandanmagsar B and Dixit VD. (2009) Deficient ghrelin receptor mediated signaling compromises thymic stromal cell microenvironment by accelerating thymic adiposity. J. Biol. Chem. 284: 7068-7077.
Dixit VD, Yang H, Cooper-Jenkins A, Giri BB, Patel K, Taub D. (2009) Reduction of T cell-Derived Ghrelin Enhances Proinflammatory Cytokine Expression: Implications for Age-Associated Increases in Inflammation. Blood 113: 5202-5205.
Dixit VD. (2008) Hormonal, neural, and metabolic regulation of immunity. J Leukoc Biol. 84: 881. (Editorial for JLB special issue)
Dixit VD. (2008) Adipose-Immune interactions during obesity and caloric restriction: reciprocal mechanisms regulating immunity and health span. J Leukoc Biol. 84: 821-892. (Featured Article for JLB Cover Page)
Yang H, Dixit VD, Patel K, Vandanmagsar B, Collins G, Sun Y, Smith RG, Taub D. (2008). Reduction in hypophyseal growth hormone and prolactin expression due to deficiency in ghrelin receptor signaling is associated with Pit-1 suppression: Relevance to the immune system. Brain Behav Immun. 2008 Jun 17. [Epub ahead of print]
Yang H, Youm YH, Nakata C and Dixit VD. (2007) Chronic Caloric Restriction Induces Forestomach Hypertrophy with Enhanced Ghrelin Levels During Aging. Peptides. 10: 1931-1936.
Dixit VD, Yang H, Sun Y, Youm YH, Weeraratna AT, et al. (2007). Ghrelin promotes thymopoiesis during aging. J. Clin. Invest. 117: 2778-2790.
* Article Selected as Editors Highlight in JCI.
Dixit VD, Weeraratna AT, Yang H, Bertak, D, Cooper-Jenkins A, Riggins GJ, Eberhart C, Taub DD. (2006) Ghrelin and growth hormone secretagogue receptor constitute a novel autocrine pathway in astrocytoma motility. J. Biol. Chem. 281: 16681-16690.
Dawson HD, Collins G, Pyle R, Key M, Weeraratna A, Dixit VD, Nadal CV and Dennis D Taub. (2006)Direct and Indirect Effects of Retinoic Acid on Human Th2 Cytokine and Chemokine Expression by Human T Lymphocytes. BMC Immunology. 7: 27.
Arumugam TV, Chan SL, Yilmaz G, Jo DG, Tang SC, Gleichmann M, Cheng A, Okun A, Dixit VD, Xin O, Miele L, Magnus T, Granger DN and Mattson MP (2006). Gamma Secretase-Mediated Notch Signaling Worsens Brain Damage and Functional Outcome in Ischemic Stroke. Nat. Med. 12(6):621-623.
Dixit VD and Taub D. (2005) Ghrelin and Immunity: A Young Player in an Old Field. Exp. Geron. 40: 900-910.
41. Dixit VD, Schaffer EM, Pyle RS, Collins GD, Sakthivel SK, Palaniappan R, Lillard Jr JW and Taub DD. (2004). Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. *J Clin. Invest. 114: 57-66.
- Article selected as Editors Highlight in July 1st 2004 issue of J. Clin Invest.
- Article selected for commentary in Science SAGE KE, July 14th 2004.
- Article selected by NIH for an advertisement in Nature highlighting NIA-Intramural Research Programme. http://www.nature.com/naturejobs/2006/060601/full/nj0118.html