In the Chellappa Lab, we investigate metabolism across biological scales using an integrated systems biology approach.
Systemic resilience in aging
Aging is associated with an increase in frailty and loss of resilience to recover from stress and environmental exposures. We use stable-isotope tracing and metabolomics to establish a road map of metabolism across ages under various environmental states. We then examine the relevance of altered pathway activities in driving frailty and resilience.
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Metabolic cross-talk between the host and microbiome in healthy and diseased states
The composition and functional capacity of the microbiome changes with age. We develop and use mouse models cohabited with a broad spectrum of microbial ecosystems including gnotobiotic, specific pathogen free, and dirty mice to study the interplay between the host and microbiome in driving host physiology during aging and metabolic diseases.
Microbial NAD metabolism: Host Physiology and drug targets
Nicotinamide adenine dinucleotide (NAD) is a well-studied redox cofactor and a cosubstrate for signaling enzymes in the host. We investigate NAD metabolism in the gut microbiome and address their implications to host physiology. We recently established that NAD precursors are shared between the host and gut microbiome. To investigate the contributions of microbial NAD metabolism to metabolic and phenotypic outcomes in the host and vice versa we manipulate gut microbiome and use transgenic mouse models. We are also interested in developing strategies to target microbial NAD metabolism.
Transport of small molecules
Metabolism is compartmentalized at the levels of organs, cell types, and organelles. This is partly achieved by the selective transport of metabolites into various compartments. We dissect the spatiotemporal regulation of the movement of molecules across lipid bilayers and establish their implications on cellular metabolism in health and diseases. We use combinatorial approaches including CRISPR screens, metabolic profiling, stable and radioactive tracers, and biochemical assays to understand the transport mechanisms of small molecules.