Robertson, R. Paul, MD
Training in islet gene regulation and pancreas/islet transplantation programs.
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Islet Biology\Beta Cell Transcription Regulation, Islet Biology\Hormone Secretion and Exocytosis, Transplantation
Type of Grant: Mentor Based Postdoctoral Fellowship
Project Start Date: July 1, 2010
Project End Date: June 30, 2014
The applicant proposes a training grant for post-doctoral work in basic and clinical rersearch. The two projects center on 1) mechanisms for glucose toxicity of the beta cell in type 2 diabetes in humans and 2) better understanding of the metabolic consequences of successful pancreas and islet transplantation in type 1 diabetic recipients. The post-doctoral fellow participates in a broad array of basic science methodologies as well as sopistocated measures of islet function and insulin senstitivity in human subjects. The fellow experiences intense one-on-one interactions with the mentor, whose work in these areas has been fully funded by NIH, ADA, and JDRF for over 30 years, and who has an extensive track record in training fellows who remain in diabetes research.
Mentor: R. Paul Robertson, MD Postdoctoral Fellow: Jana Mahadeven, PhD
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
The overall goal of our work is to understand the way the body regulates appetite and body weight. Type II diabetes is tightly correlated with obesity and a greater ability to prevent or treat obesity will also lead to a decrease in the prevalence of type II diabetes. My particular work focuses on the hormone leptin which is produced by fat tissue. High levels of leptin tell our brains to stop eating and use more energy. Leptin is also important for maintaining sensitivity to insulin, which is notably decreased in type II diabetes. Importantly, this hormone signal is often dysfunctional in obese individuals and high levels of leptin are largely ignored by the brain. Because of this, leptin is unable to decrease body weight and maintain insulin sensitivity as it does in the healthy individual.
My specific project focuses on studying the molecular events involved in leptin action with the goal of understanding why the brain is resistant to leptin in the context of obesity. Specifically, I am studying the role of Jak2, and enzyme important to leptin function, and the way its activity is regulated by small molecular tags called phosphate groups.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
While it may seem like mapping phosphorylation sites is far removed from the treatment or prevention of diabetes, work like this is crucial to the long-term development of next generation cures and preventions. Basic science research is necessary to build greater understanding of how the human body works in both normal and diseased states. Greater knowledge derived from this research will reveal ways in which we can intervene and either prevent or treat the disease. Regarding my work in particular, Jak2 is very important to the leptin signaling pathway which is, in turn, very important in regulating appetite and body weight. Perhaps, insights gaining from studying Jak2 will be useful in developing a treatment that can suppress appetite in obese individuals. Developing effective treatments for obesity will certainly have a favorable impact in the incidence and prevalance of diabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Diabetes is a major health concern to millions of Americans and its incidence and prevalence is likely to grow of the coming years and decades. My training in medical school has shown me the difficulty of living with diabetes. I have also seen the serious complications that can arise from this disease which are detrimental to quality-of-life and may even be life threatening. However, I have also seen how advancements in our understanding of the disease produced by basic science research have led to the discovery of effective treatments for diabetes. Therefore, I am very interested in continuing this type of research with the goal of expanding the knowledge base from with treatments can be derived. Research in this area has the potential for excellent bench-to-bedside transitions and it is an exciting time to be working in this field.
This award in particular will allow me to dedicate my time towards the goals of my project. This award is necessary for allowing me to take time away from medical school to pursue these research interests. Funding such is this is crucial for supporting medical students who wish to pursue research while in school. This award will also be helpful in paying for some of the equipment and reagents that will be needed to carry out the goals of my proposal.
In what direction do you see the future of diabetes research going?
It has become clear in recent years that the increased incidence of type II diabetes is highly correlated with the increase in obesity. A number of mechanisms have been proposed to account for this. Many of the systems that regulate glucose and insulin homeostasis are also involved in the regulation of appetite and body weight. Furthermore, high amounts of body fat present in obesity seem to promote insulin resistance, which is a prominent feature of type II diabetes. Therefore, a growing amount of diabetes research has focused on the body's control of energy balance and its dysfunction in the context of obesity. This approach is highly relevant to diabetes prevention and opens up a new approach to dealing with this disease. We hope that insights derived from this research will point to novel approaches for treating or preventing both obesity and diabetes.
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