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 (Hallmarks of the Metabolic Secretome, Trends in Endocrinology and Metabolism, 2023) . 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.
Discover new functions for orphan ligands and their receptors
We are using genetic models to functionally characterize orphan or understudied cell-surface receptors (Bielzcyk-Macynska, Nat Comm. 2022). We are also developing computational structural models to better predict a putative receptor for an orphan ligand (Danneskiold-Samsoee, BioRxiv, 2023).
Identification of nutrient-sensing ligands that regulate metabolism
How do cells know which nutrients to take up and when? Our lab has discovered several secreted factors that control glucose uptake or energy regulation, including Slit2-C (Svensson et al., Cell Metab, 2016) and Isthmin-1 (Jiang, Zhao, Voilquin et al., Cell Metab, 2021) and (Zhao et al., eLife 2022)
We are currently exploring these 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 (Wei et al., Cell Metab. 2023).
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 (Coassolo et al, Current Opinion in Pharmacology, 2022), and in the secretion of cell-type specific proteins. We have developed protocols to isolate and study heterogeneous cell populations from tissues (Jung et al., STAR protocols 2020). We are using proteomics and single-cell approaches (Coassolo et al., iScience, 2022) and CRISPR gene editing to resolve the cellular landscape during disease progression and to provide a resource for the development of novel therapeutic strategies.
