Morris F. White

Department of Medicine, Endrocrine Division
Howard Hughes Medical Institute/Children's Hospital
Karp Research Building, Room 04210
300 Longwood Ave.
Boston MA 02115
Tel: (617) 919-2486
Fax: (617) 730-0244
Email: morris.white@childrens.harvard.edu
Web Page: The White Lab Page
10 postdoctoral fellows, 4 research assistants

Our laboratory studies the molecular mechanisms of insulin signal transduction to understand the integrated regulation of peripheral and central regulatory mechanism controlling nutrient homeostasis.  This scientific platform can lead to the discovery of rational treatments for diabetes and its life-threatening complications.  Our work also extends to other aspects of molecular physiology, including obesity and infertility; cardiovascular and vascular disease; retinal disease; and the regulation of life-span. Recently, our studies of the insulin-signaling network reveal common elements that promote peripheral insulin action, pancreatic b-cell growth and function, and hypothalamic control of nutrient homeostasis and fertility.  Our work also relates to brain diseases such Alzheimer and Huntington's; and certain forms of cancer might be understood through our work.  However, our immediate goal is to reveal new strategies to safely treat dysregulated nutrient metabolism that progresses to diabetes and dementia, and reduces life-span.

Most projects in the laboratory involve cell-based signaling studies, mouse-based molecular physiology, or reagent building.  We use cell-based experiments to explore the relation between signaling cascade and the control of metabolic pathways and gene expression.  The cell-based experiments reveal important relations between molecules that can be studied in genetically altered mice.  Mouse models are used to explore the integrated regulation of peripheral and central nutrient homeostasis.  Trainees are exposed to an environment that values the information available from cell- and mouse-based approaches, learning the strengths and weaknesses of each.

Recently, we have initiated efforts to generate novel reagents that will extend our understanding of the molecular basis of diabetes, and help develop strategies to prevent or cure the disorders.  First, we are identifying new compounds that can promote regeneration of pancreatic beta-cells.  Initially, this involves screening chemical libraries for small molecules that induce the expression of the insulin receptor substrate 2 in human islets.  Compounds with this property will have the potential to restore glucose homeostasis in diabetic patients.  The second project involves the generation of site-specific phosphoserine monoclonal antibodies that can be used to determine the role of Ser/Thr-phosphorylation in the regulation of insulin signaling.  Combining these reagents with our cell-and mouse-based work provides new opportunities to advance our understanding of integrated metabolism in health, disease and aging.

Training in our lab is a mentor-based, self-directed program of original investigation. Everyone is encouraged to be creative and collaborative, and to discover new information and develop novel paradigms that advance our understanding of signal transduction and diabetes.  Individual initiative and intellectual independence is strongly encouraged at an early stage.  Moreover, integration of previous experience each student brings to the laboratory serves to expand our approaches to metabolic disease.

References:

• White MF. Insulin signaling in health and disease. Science. 2003 Dec 5;302(5651):1710-1.
• Dong X, Park S, Lin X, Copps K, Yi X, White MF. Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth. J Clin Invest. 2006 Jan 4;116(1):101-114.
• Park S, Dong X, Fisher TL, Dunn S, Omer AK, Weir G, White MF. Exendin-4 uses irs2 signaling to mediate pancreatic Beta cell growth and function. J Biol Chem. 2006 Jan 13;281(2):1159-68.
• Lin, X, Taguchi, A, Park, S, Kushner, JA, Li, F, Li, Y, White MF. Dysregulation of Irs2 in b-cells and brain causes obesity and diabetes. J. Clinical Invest. J. Clinic Invest 2004 Oct 114(7):908-916.