BBS Faculty Member - Morris White

Morris White

Professor of Pediatrics, Division of Endocrinology, Department of Medicine

Boston Children's Hospital
Karp Bldg., Rm. 4210
300 Longwood Ave.
Boston, MA 02215
Tel: 617-919-2846
Fax: 617-730-0244
Email: morris.white@childrens.harvard.edu
Lab Members: 10 postdoctoral fellows, 3 research assistants
Visit my lab page here.



We investigate the molecular basis of insulin-like signaling to understand the pathophysiology of metabolic disease that progresses to diabetes and its related disorders—including obesity and infertility; cardiovascular; retinal disease; and the regulation of life-span. Our studies reveal common elements that promote peripheral insulin action, pancreatic beta-cell growth and function, and hypothalamic control of nutrient homeostasis and fertility. Moreover, certain forms of cancer might be understood through our work, and our work also relates to brain diseases and life span. Our immediate goal is to reveal new strategies to treat dysregulated nutrient metabolism that progresses to diabetes.

We use cell-based and mouse-based experimental strategies to investigate the integrated physiology of insulin-like signaling. Although far reaching, this approach focuses upon a manageable set of experiments by restriction our attention to the insulin receptor substrates (IRS1 and IRS2). IRS-proteins are adapters that integrate the metabolic and mitogenic effects of insulin and insulin-like growth factor-1 with other common signaling cascades.
Tissue specific disruption of the IRS1 and IRS2 alleles in mice is remarkably informative. In the endocrine pancreas, the deletion of IRS2 reveals an important mechanism controlling beta cell proliferation and regeneration. In the brain, IRS2 was found to coordinate appetite regulation with peripheral insulin resistance—it also shows how reduced exposure of the brain to insulin can have beneficial effects upon life span. The deletion of IRS1 and IRS2 in liver demonstrates that constitutively active Foxo1 causes hyperglycemia, and that the Akt?Foxo1 branch of insulin signaling is largely responsible for hepatic insulin-regulated glucose homeostasis and somatic growth. Similar strategies will continue to be employed in the years ahead to better understand how insulin-like signaling can consolidate our understanding of metabolic disease and diabetes with cancer progression, dementia and life-span.

Training in our laboratory 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. Each new student brings a wealth of new ideas to the laboratory that expand our capacity to approach complex biological questions in novel ways. Using a variety of molecular, cellular and physiological techniques each new student can explore the regulation of neurodegeneration and longevity, hypothalamic nutrient homeostasis, pancreatic beta cell regeneration, mitochondrial function, hepatic and muscle metabolism and growth. Our laboratory has prepared successfully several BBS students for productive careers in academia, medicine and industry.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

White MF. Insulin signaling in health and disease. Science. 2003 Dec 5;302(5651):1710-1.

Taguchi A, Wartschow LM, White MF. Brain IRS2 signaling coordinates life span and nutrient homeostasis. Science. 2007 Jul 20;317(5836):369-72.

Jinhua Wu, Yolanda D Tseng, Chong-Feng Xu, Thomas A Neubert, Morris F White, Stevan R Hubbard. Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2. Nature Structural and Molecular Biology. 2008 March; 15(3): 251-258.

Dong XC, Copps KD, Guo S, Li Y, Kollipara R, DePinho RA, White MF. Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metabolism 2008 July 2; 8(1): 65–76.



© 2013 by the President and Fellows of Harvard College