Department of Internal Medicine
Endocrine-Metabolism Faculty
Medical School:
The University of Iowa
Residency:
University of Texas
Southwestern Medical Center
Fellowship:
University of Texas
Southwestern Medical Center
Christopher M. Adams, M.D., Ph.D.
Associate Professor
Our research is primarily focused on the pathogenesis and treatment of skeletal muscle atrophy, a common and debilitating condition that lacks a pharmacologic therapy. We recently investigated how two prototypical causes of muscle atrophy (prolonged fasting and spinal cord injury) alter global mRNA expression in human skeletal muscle. Those data elucidated several novel potential mediators of human muscle atrophy, including the transcription factor ATF4. Using mouse models, we subsequently found that ATF4 is necessary and sufficient for skeletal muscle atrophy. We are now working to understand the upstream signaling mechanisms that regulate skeletal muscle ATF4 expression, the downstream mechanisms by which ATF4 causes atrophy, and whether inhibition of skeletal muscle ATF4 expression prevents and/or reverses age-related muscle atrophy (sarcopenia).
In addition to advancing our understanding of muscle atrophy, our human studies allowed us to search for a potential therapy for muscle atrophy. First, we used human data to generate unbiased mRNA expression signatures of muscle atrophy. Next, we used muscle atrophy signatures in conjunction with the Connectivity Map to identify ursolic acid (a natural compound enriched in apples) as a predicted inhibitor of atrophy-associated gene expression. Then, using mouse models, we found that ursolic acid reduced muscle atrophy and stimulated muscle hypertrophy. It did so by enhancing skeletal muscle insulin/IGF-I signaling, and inhibiting atrophy-associated skeletal muscle mRNA expression. Importantly, ursolic acid’s effects on muscle were accompanied by reductions in adiposity, fasting blood glucose and plasma cholesterol and triglycerides. These findings identify a potential therapy for muscleatrophy and perhaps other metabolic diseases, such as obesity and type 2 diabetes. Thus, we are now investigating whether ursolic acid might be a useful therapy for human patients.
Honors and Awards
- Alpha Omega Alpha Medical Honor Society, 1994
- Medical Scientist Training Program, University of Iowa, 1992-1999
- William Wilson Award, University of Iowa Department of Internal Medicine, 1999
- Physician Scientist Training Program, UT Southwestern, 1999-2005
- Clinical Scientist Development Award, Doris Duke Charitable Foundation, 2009
Recent Publications
- Kunkel SD, Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, Alipour F, Shields RK, and Adams CM. mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass. Cell Metabolism. 13: 627-638, 2011.
- Adams CM, Suneja M, Dudley-Javoroski S, and Shields RK. Altered mRNA expression after long-term soleus electrical stimulation in humans with paralysis. Muscle Nerve. 43: 65-75, 2011.
- Ebert SM, Monteys A, Fox DK, Bongers KS, Shields BE, Malmberg SE, Davidson BL, Suneja M, and Adams CM. The transcription factor ATF4 promotes skeletal myofiber atrophy during fasting. Mol Endocrinol. 24: 2565-2573, 2010.
Links of Interest