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 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 several secreted factors that control glucose uptake or energy regulation, including Slit2-C and Isthmin-1.
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-Macynska, Nat Comm. 2022
Proteomics and single-cell RNA sequencing to identify metabolic adaptations
Heterogeneity is a well-documented phenomenon resulting in cellular diversity and cell specialization in an organism. This heterogeneity is also contributing to differences in cellular signals and responses and in the secretion of cell-type specific proteins. We have developed protocols to isolate and study heterogeneous cell populations from tissues. We are using proteomics and single-cell approaches and CRISPR gene editing to resolve the cellular landscape during disease progression and to provide a resource for the development of novel therapeutic strategies. We are currently exploring metabolic pathways by using proteomic approaches and secretome analyses to understand how peripheral tissues such as adipose tissue, muscle, liver, brain and the small intestine communicate with each other.
Jung et al., STAR protocols, 2020
