Neil Ruderman, MD, DPhil (Oxon.)

Professorneil-ruderman

Education:

MD,  U. of Pittsburgh

DPhil, Oxford, UK

Postdoctoral training, Joslin Research Lab, Harvard Medical School

General field of research:

Diabetes and Metabolism

Affiliations other than medicine:

Evans Center for Interdisciplinary Biomedical Research

Contact information:

Office and Lab:

Boston Medical Center, EBRC #825, Diabetes Research Unit, 650 Albany Street, Boston, MA 02118

Phone: (617)-638 7080

Fax: (617)-638 7094

nrude@bu.edu

Research group information

Yasuo Ido, MD, PhD; Assistant Professor of Medicine, Co-Director Vascular Research; yido@bu.edu

Asish Saha, PhD; Research Associate Professor of Medicine; aksaha@bu.edu

Sayon Roy, PhD; Associate Professor of Medicine; sayon@bu.edu

Fan Lan, MD; Research Associate; fanlan@bu.edu

José Cacicedo, PhD; Postdoctoral Fellow; cacicedo@bu.edu

X. Julia Xu, PhD; Postdoctoral Fellow; juliaxu@bu.edu

Lauren Nelson; MD/PhD Student; nels@bu.edu

Keywords:

Diabetes; Atherosclerosis; Exercise; AMPK; Sirt1; Metabolic regulation.

Summary of research interest:

Our unit for many years has examined the concept that dysregulation of fuel (glucose and fatty acid) metabolism contributes to the pathogenesis of type 2 diabetes and its complications. In addition we have examined at a mechanistic level how exercise may be therapeutically useful in treating and preventing these disorders. Over the past 10-15 years we have demonstrated that exercise acts at least in part by activating in many tissues AMP-activated protein kinase (AMPK), a fuel sensing enzyme that in response to a decrease in cellular energy state increases metabolic processes (e.g. fatty acid oxidation) that generate ATP and inhibits others (e.g. lipid synthesis) that consume ATP, but are not acutely necessary for survival. In the process we have identified many endogenous (e.g. adiponectin, IL-6) and exogenous (e.g. thiazolidinediones) AMPK activators and have demonstrated that AMPK protects endothelial cells, adipocytes and retinal pericytes against the insulin resistance, inflammation, mitochondrial dysfunction, and apoptosis caused by excess glucose and fatty acid and inflammatory cytokines. Most recently we have described a link between AMPK and Sirt1, a histone/protein deacetylase that has been linked to the increase in longevity caused by calorie restriction.

Recent publications:

Ruderman, N.B., Chisholm, D., Pi-Sunyer, X., Schneider S. 1998. The Metabolically-Obese, Normal-Weight Individual: Revisited. Diabetes 47: 699-713.

Ido, Y., Carling, D., Ruderman, N.B. 2002. Hyperglycemia-induced apoptosis in human umbilical vein endothelial cells: inhibition by the AMP-activated protein kinase activation. Diabetes, 51(1): 159-67.

Tomas, E., Tsao, T.-S., Saha, A.K., Murrey, H.E., Zhang, C.C., Itani, S.I., Lodish, H.F., Ruderman, N.B. 2002. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl CoA carboxylase inhibition and AMP-activated protein kinase activation. PNAS, 99(25): 16309-13.

Ruderman, N.B., Prentki, M. 2004. AMP Kinase and Malonyl-CoA: Targets for Therapy of the Metabolic Syndrome. Nature: Drug Discovery 3(4):340-51.

Ruderman, N.B., Shulman, G.I. 2009. “The metabolic syndrome.” In De Groot L.J., Jamieson, J.L., Endocrinology, 6th Ed. Philadelphia, Elsevier, Saunders, In press.

Gauthier MS, Miyoshi H, Souza SC, Cacicedo JM, Saha AK, Greenberg AS, Ruderman NB. 2008. AMP-activated protein kinase (AMPK) is activated as a consequence of lipolysis in the Adipocyte: Potential mechanism and physiological relevance. J Biol Chem. Jun 13;283(24):16514-24.

Lan F., Cacicedo J.M., Ruderman N., Ido Y. 2008. SIRT1 modulation of the acetylation status, cytosolic localization and activity of LKB1; possible role in AMP-activated protein kinase activation. J Biol Chem 283(41): 27628-35.

Richter, E., Ruderman, N.B. 2009. AMPK and the biochemistry of exercise: Implications for human health and disease. The Biochemical Journal, 418(2): 261-75.

Technologies available for sharing upon request:

Spectrophotometric and fluorometric metabolite assays of metabolic intermediates; Techniques for incubating skeletal muscle; Exercise studies in mice and rats.