SvenssonLab@Stanford
 
 

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

Novel secreted regulators of glucose and lipid metabolism in the development of metabolic diseases. Diabetologia. 2024

Size matters: the biochemical logic of ligand type in endocrine crosstalk. Life Metabolism. 2023

New players of the adipose secretome: Therapeutic opportunities and challenges, Current Opinion in Pharmacology 2022


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

Zhao et al., eLife 2022

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 are also developing computational structural models to better predict putative receptors for orphan ligands.

Bielzcyk-Macynska, Nat Comm. 2022

Danneskiold-Samsoee, BioRxiv, 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 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

Coassolo et al., iScience, 2022

Wei et al., Cell Metab. 2023

 
 
 
 

In the realm of pathways that signal and sway,

Our research aims to understand, each day,

Metabolism's regulation, a dance divine,

How cells and organs together entwine.

 

To answer how communication flows,

In metabolic homeostasis, as life unfolds,

Secreted molecules, peptides unseen,

Interpreting signals, a cell's routine.

 

Fasting, feeding, and nutrients in excess,

Regulating ligands, nature's finesse,

Endocrine, paracrine, or autocrine ways,

Controlling metabolism, in life's grand ballet.

 

Orphan ligands, their secrets to share,

Receptor-mediated tales, knowledge rare,

The diversity of signaling, mechanisms untold,

Cell-type specific tales to enfold.

 

Long-term aspirations, knowledge to glean,

Nutrient-dependent metabolism, a dream,

Mechanisms revealed, health to embrace,

With new technologies, peptides we'll trace.

 
 
 

FUNDING AND AFFILIATIONS

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“It is not the strongest of the species that survives, nor the most intelligent, but the ones most adaptable to change.”

charles darwin

 
 
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