News & Research

    Children's Hospital Boston, Boston, Massachusetts

The molecular basis of insulin signal transduction

General Research Subject: Type 2 Diabetes

Focus: Insulin Action, Insulin Action\Metabolism, Insulin Action\Signal Transduction, Islet Biology, Islet Biology\Beta Cell Growth and Differentiation

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2012

Project End Date: June 30, 2016

Research Description

This ADA mentor-based fellowship investigates molecular mechanisms of insulin signal transmission in cell-based and mouse-based experimental platforms. Through generous support from various sources--including previous ADA mentor-based fellowships--the laboratory continues to make contributions to our understanding of insulin signaling. Research training in Dr. White's laboratory is a mentor-based self-directed program of original investigation.  Fellows are encouraged to employ multiple disciplines to answer important biological questions, including various aspects of molecular biology, cell biology, cell culture, protein chemistry and enzymology.

The goal of the fellowship training is to produce academic investigators of high integrity, who are well-trained in the basic principles of contemporary medical research and prepared to establish their own independent research laboratories in medical schools and research institutes throughout the nation and around the world. To realize these goals, the ADA fellow interacts with all members of the mentor's laboratory supported by the NIH, the Howard Hughes Medical Institute, and the JDFI.  In addition, the ADA fellow has unlimited opportunities to collaborate with scientists and clinical investigators in Childrens Hospital and Harvard Medical School.  Several broad areas of research are available for training, including the function and regulation of the insulin-like signaling system in peripheral and central tissues; the regeneration of pancreatic islets; and the role of insulin-like signaling in the control of animal life span.  This training allows our fellows to face the future with courage and confidence to engage new questions and develop solutions to biological problems related to diabetes.

Research Profile

Mentor: Morris F. White, PhD  Postdoctoral Fellow: Oliver Stohr,PhD

What area of diabetes research does your project cover?  What role will this particular project play in preventing, treating and/or curing diabetes?

This ADA mentor-based fellowship investigates molecular mechanisms of insulin signal transmission in cell-based and mouse-based experimental platforms. Through generous support from various sources—including previous ADA mentor-based fellowships—the laboratory continues to make contributions to our understanding of insulin signaling. Research training in Dr. White's laboratory is a mentor-based self-directed program of original investigation.  Fellows are encouraged to employ multiple disciplines to answer important biological questions, including various aspects of molecular biology, cell biology, cell culture, protein chemistry and enzymology. The goal of the fellowship training is to produce academic investigators of high integrity, who are well-trained in the basic principles of contemporary medical research and prepared to establish their own independent research laboratories in medical schools and research institutes throughout the nation and around the world. To realize these goals, the ADA fellow interacts with all members of the mentor's laboratory supported by the NIH, the Howard Hughes Medical Institute, and the JDFI. 

In addition, the ADA fellow has unlimited opportunities to collaborate with scientists and clinical investigators in Childrens Hospital and Harvard Medical School.  Several broad areas of research are available for training, including the function and regulation of the insulin-like signaling system in peripheral and central tissues; the regeneration of pancreatic islets; and the role of insulin-like signaling in the control of animal life span.  This training allows our fellows to face the future with courage and confidence to engage new questions and develop solutions to biological problems related to diabetes.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

The goal of the fellowship project is to produce academic investigators of high integrity, who are well-trained in the basic principles of contemporary medical research and prepared to establish their own independent research laboratories in medical schools and research institutes throughout the nation and around the world.

Why is it important for you, personally, to become involved in diabetes research?  What role will this award play in your research efforts?

I have been a principal investigator studying insulin action and the insulin signaling cascades coordinated by the insulin receptor substrates since 1987.  My current research deals with the molecular mechanisms that regulate signaling through the IRS1 and IRS2 branches of the cascade, especially involving the serine and threonine phosphorylation cascades mediated by nutrient excess and physiological stress. 

We are also studying how these signaling pathways coordinate metabolic homeostasis and function of peripheral and central tissues—especially the liver, muscle, pancreatic beta cells and the brain. I have trained over 30 postdoctoral fellows and 6 graduate students—many of whom have gone on to independent faculty positions. Some of these trainees have been supported by the ADA mentor-based awards. I think the scientific progress and training that our laboratory provides can continue to be valuable toward the ultimate prevention, treatment, and cure of diabetes.

In what direction do you see the future of diabetes research going?

Now that the principle elements of the insulin signaling cascade are in place, how they respond to systemic stress and compensatory changes needs to be vigorously explored.  Understanding selective insulin responsiveness across body tissues might lead to new understanding of the paradoxical hypertriglyceridemia during insulin resistance. Exploration of these novel interactions has just begun, and can benefit from the creative investigation of genetically modified mice. Sorting out the selective insulin resistance that propagates across body tissues could open a new chapter in our search for the molecular mechanisms of life-threatening metabolic disease.