Understanding why individuals differ in their ability to maintain metabolic balance under stress is an unsolved challenge in metabolic research. Such interindividual variation in physiological adaptation and energy homeostasis drives differences in disease susceptibility, progression, and treatment response. Yet these differences cannot be fully explained by inherited genetics, pointing to additional somatic and metabolic layers of regulation. 

My laboratory investigates how energetic inefficiency, particularly through futile metabolic cycles, enables cells and tissues to adapt and maintain homeostasis. We investigate if variation in futile cycle activity contributes to short-term, reversible metabolic flexibility, while somatic mutations in metabolic tissues provide a longer-term, cell-specific layer of adaptation. Together, these processes may underlie the unexplained diversity of metabolic phenotypes observed across individuals. 

Using mechanistic biochemistry, genetic perturbation, and single-cell and multi-omics analyses, we aim to dissect how futile lipid cycling modulates signaling and identify how somatic mosaicism reprograms metabolic circuits ((in)dependent of futile cycling). By quantitatively linking energetic inefficiency and somatic variation, our research will establish a new framework for understanding adaptive homeostasis, offering insights into metabolic resilience, disease heterogeneity, and opportunities for novel metabolic therapy modalities.