Department of Medicine

Laboratory of Robert M. O’Doherty, PhD

E1154 BST – Office; E1112, E1104 BST – Labs
Phone: 412-648-3320
FAX: 412-648-3290
e-mail: odohertyr@dom.pitt.edu
School of Medicine: www.medschool.pitt.edu/
Division of Endocrinology: www.dom.pitt.edu/endo/
Dept of Micro/Molecular genetics: www.mmg.pitt.edu/

Robert M. O’Doherty, PhD

A little about me…….
I graduated from Trinity College Dublin, Ireland in 1986 with a BA (Mod) in Zoology (marine biology) and in 1995 obtained a PhD from Vanderbilt University, Nashville, TN., USA in Molecular Physiology, with a focus on insulin action. After completing a post-doctoral fellowship at UT Southwestern (with a focus on dysregulated metabolism and gene therapy in diabetes/obesity) I joined the faculty of the Departments of Medicine (Division of Endocrinology and Metabolism) and Microbiology and Molecular Genetics at the University of Pittsburgh in 1999.  I am currently an Associate Professor of Medicine, and Microbiology and Molecular Genetics.

The Science……..
Our group is focused on basic research, with a growing interest in translating observations made in our models to human disease states.  The research focus of the group is the biochemical and molecular mechanisms that link obesity, insulin resistance, dyslipidemia and inflammation in the metabolic syndrome (MS). MS comprises a clustering of risk factors (obesity, insulin resistance, dyslipidemia/steatosis, inflammation, hypertension and altered thrombotic status) that dramatically increase the risk of developing diabetes and coronary vascular disease (CVD).  As such MS is an extremely serious public health problem that consumes excessive health care resources. Thus, understanding the causes of MS and identifying biochemical drug targets for the treatment of MS is a high priority. A major focus of our current research efforts is determining the mechanisms that link steatosis (excessive lipid storage in tissues) and insulin resistance and the role of increased activity of the innate immune system/inflammatory pathways in the pathogenesis of insulin resistance.  In this regard, there is growing evidence that inappropriate activation of the immune system may play a role the development of insulin resistance and type II diabetes in obesity.  Furthermore, dyslipidemia (elevated fats) are a primary candidate for the activation of inflammatory pathways and insulin resistance.

Outstanding people makes the science happen. Those people currently in the O’Doherty group are…..

And this is what they have done recently,……..

1.    Huang, W, N Dedousis, BA Bhatt, RM O'Doherty.  Impaired activation of phosphoinositol 3-kinase by leptin is a novel form of hepatic leptin resistance in diet-induced obesity. J.Biol.Chem. 279:21695-21700, 2004
2.    Sinha S, G Perdomo, NF Brown, RM O’Doherty. Fatty acid-induced insulin resistance in L6 myotubes is prevented by inhibition of activation and nuclear translocation of NFB. J.Biol.Chem, 279:41294-41301, 2004
3.    Perdoma G, SR Commerford, SH Adams, B Corkey, RM O'Doherty, NF Brown. Increased b-oxidation in muscle cells enhances insulin-stimulated glucose metabolism and protects against fatty acid induced insulin resistance despite intramyocellular lipid accumulation. J.Biol.Chem. 279:27177-27186, 2004
4.    Bhatt BA, JJ Dube, N Dedousis, J Alton-Reider, RM O'Doherty. Diet-induced obesity and acute hyperlipidemia reduce IkBa levels in rat skeletal muscle in a fiber-type dependent manner. Am J Physiol 290: R233-R240, 2006.
5.    Huang W, N Dedousis, A. Biyani, RM O'Doherty. Hepatic triglyceride secretion and lipid oxidative metabolism are rapidly altered by leptin in vivo.  Endocrinology, 147:1480-1487, 2006
6.    Bhatt, BA, RM O'Doherty.  Insulin resistance, inflammation, and the NF-kB pathway. IN Advances in   Molecular and Cellular Endocrinology; New Transcription Factors and their Role in Diabetes and its Therapy, Ed: JE Friedman, Elsevier, 2006
7.    Huang W, N Dedousis, RM O'Doherty. Hepatic steatosis and plasma dyslipidemia induced by a high    sucrose diet are corrected by an acute leptin infusion. J.App.Phys. 102:2260-2265, 2007
8.    Dube JJ, BA Bhatt, N Dedousis, A Bonen, RM O’Doherty. Leptin protects against insulin resistance induced by acute hyperlipidemia. Am. J. Physiol.293:R642-R650, 2007
9.    Radin MS, S Sinha, BA Bhatt, N. Dedousis, RM O’Doherty. Toll-like Receptor-4 mediates palmitate and lipopolysaccaride activation of the IKK/IkB/NFkB pathway in skeletal muscle. Diabetologia. 51:336-346, 2008
10.  Stefanovic-Racic M, G Perdomo, BS Mantell, IJ Sipula, NF Brown, RM O’Doherty. A moderate increase in carnitine palmitoyl transferase I activity is sufficient to substantially reduce hepatic triglyceride levels. Am. J. Physiol. In Press

The finance to support the people and the science is provided by the National Institutes of Health and the American Diabetes Association. Notable recent awards are…

Completed
1. American Diabetes Association (Career Development Award)
 “The role of hepatic leptin receptors in mediating the metabolic actions of leptin”
P.I.: O’Doherty                     Period: 01/01-12/04             Award: $500,000

Active:
1. American Diabetes Association (Research Award)
"Insulin resistance and the IKK/IkB/NF-kB pathway"
P.I.: O'Doherty                      Period: 01/05-12/07

2. NIH/NIDDK RO1 DK058855-05
"Lipids, Inflammation, and Insulin Resistance"
P.I.: O'Doherty Period: 07/06-06/10

3. NIH/NIDDK RO1 DK072162-01
"Hepatic Leptin Resistance and Leptin Action"
P.I.: O'Doherty Period: 07/06-06/11

And finally, the people of the past whose contributions made the present possible…….