Radhakrishnan, Ishwar , PhD
Transcription Regulation of Gluconeogenic Genes by CREB/ATF and TORC Factors
General Research Subject: Type 2 Diabetes
Focus: Signal Transduction (Non-Insulin Action)
Type of Grant: Basic Science
Project Start Date: January 1, 2012
Project End Date: December 31, 2014
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
My project focuses on the etiology of type 2 diabetes, with emphasis on proteins that regulate the levels of enzymes involved in glucose production. Our proposed studies seek to clarify how the CREB/ATF family of transcription factors - which bind DNA - elevate the levels of these enzymes by increasing the cellular levels of the corresponding mRNAs. Recent studies have shown that the CREB/ATF factors recruit the TORC family of transcriptional coactivators to regulate transcription of key gluconeogenic enzymes. We plan to capture atomic resolution snapshots of TORCs interacting with CREB/ATF factors at the molecular level. This will tell us the features of the two proteins that are important for function. This knowledge can be used to design and develop small molecules that can block the interaction and potentially function as drugs for treatment of type 2 diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
My research project can help finding a way to manage diabetes. Detailed knowledge of how proteins interact at the molecular level have been vital to drug development programs both in the pharmaceutical industry as well as in the academia. I can see our research having a direct bearing on the discovery of compounds that block relevant protein-protein interactions and help regulate glucose levels in the body.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Obesity and type 2 diabetes are on the rise not only in the developed world but also in many developing countries. There is no doubt that this is a serious disease for which mitigating strategies are urgently needed; it represents a major challenge for biomedical researchers in the 21st century. This has struck a chord at a personal level with friends and family members affected by the disease. Although lifestyle changes can partly address the problem, a holistic approach that includes therapeutic intervention - a la statins - is required. This is our first foray into diabetes research. Although our preliminary studies have yielded exciting results, more data in support of our hypotheses are required. Seed funding from ADA will thus be vital to our efforts to eventually gain longer-term funding from the NIH.
In what direction do you see the future of diabetes research going?
I am very optimistic of the future of diabetes research. The dimensions of the problem is concentrating minds to find ways to manage and ultimately cure the disease. The surge in discoveries of new and important pathways that impact on this disease coupled with ready access of drug discovery technology to even modest-sized academic labs implies that these goals are realistic and will be attained in the near future.
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