Contact Information

Office: 3314 PBDB
Phone: 319-335-4736
Faculty Profile

Brief description of current research:

Insulin is best known for its effects on glucose metabolism, but also has a significant impact on protein synthesis and degradation, especially in muscle. Muscle wasting in response to aging or immobilization can worsen in the context of insulin resistance or uncontrolled diabetes, but how this occurs and to what extent this is connected to defects in energy production in mitochondria is unknown. We showed that insulin and IGF-1 coordinate muscle growth and prevent muscle atrophy via suppression of FoxO transcription factors. Research in the O’Neill lab is now focusing on the mechanisms of FoxO-regulated protein turnover and mitochondrial recycling via autophagy (a process known as mitophagy). Using cell and animal models, we aim to dissect how cellular signals that coordinate muscle growth and mitochondrial energy production are disrupted in the diabetic state. We hope these findings will provide new targets for therapy to help prevent disability and aging-related muscle loss in patients with diabetes. 

3 most influential diabetes/obesity/metabolism publications:

• O'Neill BT, Lee KY, Klaus K, Softic S, Krumpoch MT, Fentz J, Stanford KI, Robinson MM, Cai W, Kleinridders A, Pereira RO, Hirshman MF, Abel ED, Accili D, Goodyear LJ, Nair KS, Kahn CR. Insulin and IGF-1 receptors regulate FoxO-mediated signaling in muscle proteostasis. J Clin Invest. 2016 Sep 1;126(9):3433-46
• O'Neill BT, Lauritzen HP, Hirshman MF, Smyth G, Goodyear LJ, Kahn CR. Differential Role of Insulin/IGF-1 Receptor Signaling in Muscle Growth and Glucose Homeostasis. Cell Rep. 2015 May 26;11(8):1220-35.
• O'Neill BT, Kim J, Wende AR, Theobald HA, Tuinei J, Buchanan J, Guo A, Zaha VG, Davis DK, Schell JC, Boudina S, Wayment B, Litwin SE, Shioi T, Izumo S, Birnbaum MJ, Abel ED. A conserved role for phosphatidylinositol 3-kinase but not Akt signaling in mitochondrial adaptations that accompany physiological cardiac hypertrophy. Cell Metab. 2007 Oct;6(4):294-306.

Quote:

Critical thinking drives innovation in both science and medicine. It’s also part of the fun and fascination of what we do.