Robert Smith, MD
Professor of Medicine
Work: +1 401-444-3420
Robert Smith's current projects are investigating mechanisms of the cellular actions of the hormone insulin and the closely-related insulin-like growth factors (IGFs). These include studies on recently identified proteins in the insulin and IGF pathways that may have roles in causing diabetes, neurodegenerative disease, and disturbed metabolism in critical illness. Clinical research projects focus on the effectiveness and importance of glucose control in diabetes and on causes of human growth disorders.
BiographyRobert J. Smith joined the faculty in 2000 as director of the division of endocrinology and the new Hallett Center for Diabetes and Endocrinology. His education included a BA in biochemistry from the University of Pennsylvania, a BMS degree from Dartmouth Medical School, and an MD from Harvard Medical School. He completed internal medicine residency training at Duke University and subspecialty training in endocrinology, diabetes and metabolism at the National Institutes of Health (Bethesda, MD) and the Brigham and Women's Hospital (Boston, MA). He was a member of the faculty of Harvard Medical School from 1978-2000 with appointments at the Joslin Diabetes Center, the Brigham and Women's Hospital, and the Beth Israel Deaconess Medical Center.
His honors include the AMA Goldberger Fellowship Research Award, the Harvard division of medical ethics Responsible Conduct of Research Award, and appointment to the Howard Hughes Medical Institute. He has served on multiple editorial boards including, at present, the Journal of Biological Chemistry, Endocrinology, the Journal of Parenteral and Enteral Nutrition and the Journal of Growth Hormone and IGF Research. He has published numerous research articles, reviews and chapters, and has trained more than 70 research students and postdoctoral research fellows.
A major focus of Smith's research is on the mechanisms of cellular signaling by insulin, insulin-like growth factors and growth hormone, and the mechanisms through which changes in signaling lead to human disease. His work is directed in particular to the role of altered hormone signaling in diabetes mellitus, genetic and acquired growth disorders, and catabolic states associated with severe illness. In addition to studies on cell surface hormone receptors and intracellular signaling mechanisms, he has extensively investigated nutritional factors that are interactive with hormone signaling mechanisms. The experimental approaches utilized in his laboratory extend methodologically from basic molecular biology to clinical studies in an effort to understand the molecular basis for clinically relevant disease processes.
Research DescriptionA major focus of Robert Smith's research is on the mechanisms of cellular signaling by insulin, insulin-like growth factors, and growth hormone and the mechanisms through which changes in signaling lead to human disease. His work is directed in particular to the role of altered hormone signaling in diabetes mellitus, genetic and acquired growth disorders, and catabolic states associated with severe illness. In addition to studies on cell surface hormone receptors and intracellular signaling mechanisms, he has extensively investigated nutritional factors that are interactive with hormone signaling mechanisms. The experimental approaches utilized in his laboratory extend methodologically from basic molecular biology to clinical studies in an effort to understand the molecular basis for clinically relevant disease processes.
Studies on novel mechanisms of action of insulin and related growth factors (IGFs) in cells and tissues.
Studies on the mechanisms of resistance and/or altered signaling by these hormones in human disease states, including diabetes and cancer.
Advancing our understanding of disease mechanisms and targeting new strategies for diagnosis and treatment.
Recent work on links between diabetes and neurodegenerative diseases that has identified an important Parkinson's disease gene.
Studies on the quality of blood glucose control achieved in Rhode Island Hospital inpatients with diabetes managed by insulin IV infusions and by current post-infusion regimens.
Study on management of diabetes patients with cardiovascular disease by interventions vs medical management.
Grants and Awards1971 B.M.S. with Honors from Dartmouth Medical School
1972 AMA Goldberger Fellowship Research Award
1972-1978 National Institutes of Health (NIH) Costep Fellowship Award
1990 Elected to American Society for Clinical Investigation
1995 Harvard Division of Medical Ethics Responsible Conduct of Research Award
1999 Outstanding Science Award of the Ninth Beijing International Symposium on Parenteral and Enteral Nutrition (oral presentation by postdoctoral fellow Yilei Mao).
American Association for the Advancement of Science, Member
American Diabetes Association, Member
American Federation for Clinical Research, Member
American Society for Clinical Investigation, Member
American Society for Parenteral and Enteral Nutrition, Member
American Society of Biological Chemistry and Molecular Biology, Member
Diabetes Professional Advisory Council, Rhode Island Department of Health, Chair
Growth Hormone Research Society, Member
International Society for Insulin-like Growth Factor Research, Founding Member
Providence Professional Advisory Council, American Diabetes Association
The Endocrine Society, Member
--(1994-1997, Annual Meeting Steering Committee)
--(2001-2004, Special Programs Committee)
--(2004-2007, Chair, Clinical Endocrinology Update)
Current Editorial Boards:
Journal of Biological Chemistry
UpToDate (Diabetes Section)
Funded ResearchCurrent Research Support
Agency: National Institutes of Health (NIH) (5U01HL061744, Katherine Detre PI)
Title: BARI II: A Trial of Revascularization and Glycemic Control in NIDDM
Total direct costs: variable based on patient entry
Role: Diabetes Site PI
Agency: NIH (5R01DK059339, Charlotte Boney PI)
Title: The Role of Src Kinases in IGF-I-Mediated Adipogenesis
Total direct costs: donated effort, no salary support
Agency: NIH (5P20RR017695, Douglas Hixson PI)
Title: Cancer Center Research Development Grant
Total direct costs: $1,554,248
Agency: Brigham and Women's Hospital Royalty Research Support
Title: Glutamine Patent Royalties
Current total direct costs: $111,538
Role: Principal Investigator
Pending and in Preparation Research Support
Agency: American Diabetes Association
Title: Role of the Transcription Regulator YB-1 in Insulin Signaling and Insulin Resistance
Total direct costs requested: $260,870
Role: Principal Investigator
Agency: NIH (R01 DK43038)
Title: Function and Molecular Pathology of Grb10 Interacting GYF Protein 2 (GIGYF2)
Total direct costs requested: $1,250,000
Role: Principal Investigator
- Fanning PJ, Emkey G, Smith RJ, Grodzinsky AJ, Szasz N, Trippel SB. Mechanical regulation of mitogen-activated protein kinase signaling in articular cartilage. J Biol Chem 2003; 278: in press. (2003)
- Giovannone B, Lee E, Laviola L, Giorgino F, Cleveland KA, Smith RJ. Two novel proteins that are linked to insulin-like growth factor-I (IGF-I) receptors by the Grb10 adapter and modulate IGF-I signaling. J Biol Chem 2003; 278: 31564-31573. (2003)
- McCowen KC, Ling PR, Ciccarone A, Mao Y, Chow JC, Bistrian, BR, Smith RJ. Sustained endotoxemia leads to marked down-regulation of early steps in the insulin signaling cascade. Crit Care Med 2001; 29:839-846. (2001)
- Giorgino F, de Robertis O, Laviola L, Montrone C, Perrini S, McCowen KC, Smith RJ. The sentrin-conjugating enzyme mUbc9 interacts with GLUT4 and GLUT1 glucose transporters and regulates transporter levels in skeletal muscle cells. Proc Natl Acad Sci 2000; 97:1125-1130. (2000)
- Mao Y, Ling PR, Fitzgibbons TP, McCowen KC, Frick GP, Bistrian BR, Smith RJ. Endotoxin-induced inhibition of growth hormone receptor signaling in rat liver in vivo. Endocrinology 1999; 140:5505-5515. (1999)
- Giorgino F, Logoluso F, Davalli AM, Napoli R, Laviola L, Hirshman MF, Horton ES, Weir GC, Smith RJ. Islet transplantation restores normal levels of insulin receptor and substrate tyrosine phosphorylation and phosphatidylinositol 3-kinase activity in skeletal muscle and myocardium of streptozocin diabetic rats. Diabetes 1999; 48:801-812. (1999)