Identification of pathways and orphan hormones that are regulating metabolism
In the past decade, our understanding of our endocrine system has vastly evolved, leading to the recognition of novel molecules with endocrine functions from organs that were not previously considered to be part of the classical endocrine system. Our lab uses an integrated approach of genetic models, biochemistry, molecular biology and proteomic techniques to identify and study new hormones and their function.
Our goals are to clarify the molecular pathways of metabolic disease, develop therapeutics targeting pathways in energy expenditure, and to facilitate the development of diagnostic tools for identification of metabolic disease. Finding new pathways are important from a biological perspective to increase the understanding of complex regulation of physiology, but also offers direct methods for translational development of protein therapeutics and biomarkers.
Mechanistic insights into the metabolic role of Slit2-C in glucose and energy homeostasis
Activation of brown and beige adipose tissue has emerged as a potential strategy to treat metabolic disease. We have previously identified a fragment of a secreted factor called Slit2-C that is secreted from thermogenic adipose tissue (Svensson et al, Cell Metab, 2016). Current studies are focusing on characterizing the molecular mechanisms of action by protein therapeutic approaches, as well as identifying the Slit2-C receptor on adipocytes.
Investigating the role of a novel secreted protein, Isthmin-1 in metabolic disease
New pathways and targets that can directly regulate glucose, hepatic triglycerides and gluconeogenesis independently of insulin are essential for the development of drugs for type 2 diabetics. Isthmin-1 is a novel protein hormone secreted from adipocytes that acts independently of insulin. We are currently studying how Isthmin-1 acts to improve metabolic homeostasis using mouse models of obesity and diabetes.
Understanding the transition from non-alcoholic fatty liver (NAFLD) to non-alcoholic steatohepatitis (NASH)
A liver in the transition from healthy to fatty liver and subsequently to NASH undergoes major re-arrangements of hepatocytes and non-hepatocyte cells in the liver. A better understanding of this process is needed for the development of drugs for this disease that currently has no approved treatment. We are developing innovative model systems that will enable the study of the biology of NASH, which will provide unprecedented opportunities for novel therapies.
Development of a biomarker footprint for NAFLD and NASH
There are no early biomarkers for non-alcoholic fatty liver disease (NAFLD or NASH). The goal of this project is to identify biomarkers of early insulin resistance and hepatic steatosis as an alternative to invasive liver biopsies to diagnose or monitor treatment response.
The Svensson Lab is grateful for past and present support from the following sources: