The Shen laboratory studies cellular metabolism through the characterization of human metabolic enzymes and transporters of unknown functions. The current focus of the lab lies in the study of mitochondrial metabolite transporter SLC25 family with the application of techniques ranging from biochemistry, cell biology, CRISPR, molecular evolution, and metabolomics. The Shen lab recently discovered the critical role of a previously "orphaned" transporter SLC25A39 in mitochondrial glutathione transport, and the dual regulatory mechanism for the SLC25A39 protein, by mitochondrial protein quality control and iron sensing, that coordinates mitochondrial glutathione and iron metabolism. The discovery sheds new light on the molecular mechanism of glutathione compartmentalization and its regulation, and offers new insights into human diseases related to glutathione and metabolic compartmentalization. At Yale, Hoy was awarded CZI Collaborative Pairs Pilot Project Awards ('20, co-PI), Lois E and Franklin H. Top Jr. Yale Scholar Award ('21), Klingenstein-Simons Fellowship Award in Neurosciences ('21-'24), 1907 Foundation Trailblazer Award in mental health ('22-'23) and Rita Allen Foundation Scholar ('23-'28).
The nutrient-sensing role of circadian clock in fat and muscle
The circadian clock is entrained by metabolic cues and exerts pervasive temporal control in metabolic processes. The intricate interplay between circadian clock with nutrient signals orchestrates homeostasis. Our research focuses on deciphering the molecular and signaling pathways underlying tissue-intrinsic clocks circuits in driving metabolic tissue functional capacity. Recent studies uncovered the nutrient-sensing role of clock that governs metabolic substrate metabolism. Mechanistic interrogations of clock modulation of nutrient metabolism in adipose tissue and skeletal muscle will be discussed, together with our recent foray into targeting these mechanisms for disease applications.