Vishwa Deep Dixit
Professor of Comparative Medicine and of Immunobiology
Immune-Metabolic Interactions; Aging and age-related inflammation; Obesity-associated inflammation and metabolic syndrome; Adipose tissue leukocytosis; Inflammasomes; Thymic involution and approaches for thymic rejuvenation; Neuroendocrine control of immune system
A major goal of my research program is to obtain creative insights that advance knowledge in the field of Immune-Metabolic interactions that drive adiposity and age-related chronic diseases. Our studies focus on understanding the mechanisms and consequences of aberrant immune-cell activation in adipose tissue microenvironment and age-related ectopic adipocyte development in lymphoid microenvironment like thymus and bone marrow. 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. In addition, clinical studies are evaluating the impact of caloric excess and caloric restriction on mechanism that impact immune system. The long-term goal of our research is to understand the mechanisms of immune-metabolic crosstalk and to help develop novel approaches to regulate the aberrant immune cell activation as means to enhance healthspan.
Extensive Research Description
The NIH funded projects in the laboratory are –
R01AG031797 (National Institute on Aging)
Impact of Calorie Restriction on Thymopoiesis in Humans.
The overall goal of this randomized control trial is to study whether salutary and pro-longevity effects of calorie restriction in animal models extend to healthy aging and thymic function in middle aged humans. In this study we are analyzing the ectopic adipocyte development in the thymus using MRI and investigating the mechanism of CR’s effects on thymic function and T cell receptor repertoire diversity in humans.
Impact of Obesity and Weight-Loss Interventions on Immune-Surveillance Mechanisms.
The major goal of this study is to determine the mechanisms that link obesity to T cell function, and T cell receptor repertoire diversity. We are evaluating the neuroendocrine-immune interactions that may drive the salutary effects of various bariatric procedures or calorie restriction on metabolic and immune systems during obesity.
R01AG043608: (National Institute on Aging)
Inflammasomes and the mechanism of thymic demise in aging.
The Nlrp3 inflammasome senses metabolic ‘danger signals’ and, upon assembly, causes caspase-1 activation, which in turn controls the secretion of pro-inflammatory cytokines IL-1β and IL-18. The central hypothesis of this proposal is that age-related thymic lipotoxicity via a canonical Nlrp3 Inflammasome-dependent mechanism induces ‘sterile thymic inflammation’ and induces T cell dysfunction during aging.
R01AG045712: (National Institute on Aging)
Impact of CR on inflammasome mediated immune-metabolic interactions
The overall goal of this project is to understand whether CR’s beneficial anti-inflammatory effects observed in animals are relevant to human physiology. Through analysis of archived blood immune cells and fat tissue samples, the current application will identify clinically relevant mechanisms of regulation of inflammation.
Thymic adipogenesis and age-related thymic demise
With progressive aging, thymus is replaced with ectopic adipocytes and its ability to produce naïve T cells is dramatically diminished. This research project is designed to understand the lineage of adipocytes in aging thymus and to determine the causes and consequences of thymic adiposity and its relationship with immune-senescence.