Laboratory of metabolic regulation
@ Stanford University
Exploring the secretome for new metabolic hormones
How do tissues communicate with each other, and how is this communication altered in disease? In the past decade, our understanding of secreted factors (tissue-residing or blood-borne ) has vastly evolved, leading to the recognition of novel molecules with signaling properties from organs that were not previously considered to be part of the classical hormonal system. We are specifically interested in mapping tissue-specific peptide secretion to identify orphan neuropeptides and peptide hormones. We use protein sequence analyses, proteomics, and animal physiology approaches to study these new metabolic targets and pathways. Our goals are to better understand complex physiological systems such as obesity and aging.
Hallmarks of the Metabolic Secretome. Trends in Endocrinology and Metabolism, 2023
Size matters: the biochemical logic of ligand type in endocrine crosstalk. Life Metabolism. 2023
Discover new functions for orphan secreted peptides and their receptors
Our lab has discovered new functions for several secreted factors that control glucose uptake or energy balance, including Slit2, Isthmin-1, ANGPTL3 and BRP.
Reghupaty et al., Mol Metab, 2025
Jiang, Zhao, Voilquin et al., Cell Metab, 2021
Svensson et al., Cell Metab, 2016
Receptor action and deorphanization
We are using genetic models to functionally characterize orphan or understudied cell-surface receptors, including a function for the diabetes-associated gene GPR151. We have also developed computational structural models using AlphaFold to better predict putative receptors for orphan ligands.
Banhos Danneskiold-Samsøe Cell Systems, 2024
Bielzcyk-Maczynska, Nat Comm. 2022
Dietary sugars and metabolic dysfunction
We are interested in understanding how the uptake and metabolism of glucose and fructose drive metabolic adaptations, particularly their profound effects on liver disease and systemic metabolism. Cellular heterogeneity is a well-documented phenomenon that results in cellular diversity, specialization, and differences in cellular signals, responses, and cell-type specific protein secretion within an organism. We have developed protocols to isolate and study these heterogeneous cell populations from tissues. Through proteomic and secretome analyses, we aim to dissect the communication between peripheral tissues such as adipose tissue, muscle, liver, brain, and the small intestine, to understand their coordinated responses to these dietary sugars.
Zhao, Zhang, Garelli et al. Cell Reports, 2025
Jung et al., STAR protocols, 2020
