Lab Website: http://www.medicine.uiowa.edu/dept_primary_apr.aspx?appointment=Internal Medicine&id=cadams

Molecular Mechanisms of Skeletal Muscle Atrophy

I am a physician-scientist and practice in the areas of internal medicine and endocrinology. In many of my patients, skeletal muscle atrophy causes weakness and disability. However, muscle atrophy is poorly understood at the molecular level and lacks a medical therapy. To address these issues, my laboratory investigates molecular mechanisms of muscle atrophy and new potential therapeutic approaches to muscle atrophy. Our mechanistic studies combine patient-oriented research with basic research in mouse and cultured myotube models; through those studies, we have identified several previously unrecognized molecular mediators of muscle atrophy (e.g. ATF4, Gadd45a, p21, MEKK4), as well as a protein that helps to maintain healthy muscle but is reduced when muscle undergoes atrophy (spermine oxidase). We are currently investigating how these proteins are regulated and how they interact and contribute to muscle weakness and atrophy. To identify new ways to prevent and treat muscle atrophy, we developed and used a novel systems-based strategy to discover several small molecules, including the natural compounds ursolic acid and tomatidine, that reduce muscle atrophy, promote muscle hypertrophy, and increase strength and endurance exercise capacity. Some of these small molecules also increase brown fat, reduce white fat, and provide protection against obesity, type 2 diabetes, and nonalcoholic fatty liver disease.

PubMed link

Department/Program Affiliations:
Genetics
Internal Medicine
Molecular Medicine
Molecular Physiology and Biophysics
MSTP