Kalaany, Nada Youssef, PhD
Role of PTEN/PI3K pathway in obesity/type 2 diabetes-associated cancer incidence and progression
General Research Subject: Insulin Resistance Pre Diabetes
Focus: Insulin Action\Signal Transduction, Integrated Physiology\Amino Acid Metabolism, Obesity\Animal Models
Type of Grant: Junior Faculty
Project Start Date: January 1, 2012
Project End Date: December 31, 2014
Several recent studies indicate a strong correlation between obesity/type 2 diabetes and incidence as well as mortality from a variety of cancers, particularly those of the pancreas and the colon, two of the most common and deadly cancers in the United States. Interestingly, the sensitivity of tumors to food restriction has recently been shown in mice, to depend on a specific signaling pathway that can be activated by insulin and is frequently over-activated in cancers, (e.g. PTEN/PI3K pathway). Therefore, it is plausible that this pathway also plays a key role in tumor growth in overly fed states, such as obesity, where blood insulin levels are high. The goal of this proposal is to investigate the potential role of PI3K/Akt in the effects of obesity/type 2 diabetes on cancers of the pancreas and the colon. Using high fat feeding strategies to induce obesity in mouse models of pancreatic and colon cancers carrying activated versus non-activated PI3K/Akt tumors, the effects of obesity/type 2 diabetes on tumor growth will be studied. Non-obese mouse models of type 2 diabetes will also be utilized to control for the confounding effects of obesity. Tumors will be removed from obese or diabetic mice and transplanted into lean or non-diabetic mice, or vice versa. All mice will also be subjected to dietary and/or anti-diabetic drug interventions and the effects on tumor growth analyzed. These studies will provide a solid basis for developing anti-cancer preventive and therapeutic approaches targeted to the rising patient population suffering from obesity/type 2 diabetes.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and or/curing diabetes?
Our research focuses on obesity, insulin resistance, type 2 diabetes and their correlation with development of cancers of the pancreas and the colon. Obesity-associated cancers have been estimated to account in the US alone, for 14% and 20% of all deaths from cancer in men and women, respectively. The increasing evidence for such a correlation has urged us to propose this project, which upon accomplishment, will lay out the basis for developing future preventive and therapeutic anti-cancer drugs targeted towards the increasing patient population suffering from obesity/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?
Epidemiological studies points to a strong correlation between insulin resistance/type 2 diabetes and development of cancers in different tissues. Our project, which focuses on understanding the correlation between type 2 diabetes and cancers of the colon and the pancreas, will form the basis for the generation of future preventive and therapeutic anti-cancer strategies targeted towards the increasing patient population suffering from type 2 diabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Equipped with a strong background in metabolic and cancer studies that I acquired throughout both my graduate and post-doctoral studies, I have become highly interested in understanding how the body metabolic status can influence the growth and survival of tumor cells. With the worldwide pandemic surge of obesity and type 2 diabetes and their costly overwhelming complications, my interests have peaked in the cancer connection, especially that, unlike cardiovascular diseases, this type 2 diabetes complication has been under-investigated. Receipt of the prestigious ADA Junior Faculty Award greatly accelerates my proposed work and will allow for the accomplishment of my scientific goals in identifying the molecular mechanisms that underlie the correlation between obesity/type2 diabetes and cancers of the pancreas and the colon. Such a correlation is of high global relevance, given the steadily increasing patient population suffering from the metabolic syndrome.
In what direction do you see the future of diabetes research going?
I see diabetes research moving towards both Prevention and Cure: Prevention: mainly through preventing obesity, an epidemic that surged during the last quarter of the twentieth century and has lead to an overwhelming increase in the number of patients suffering from the metabolic syndrome and type 2 diabetes. Therapy: Given the increasing number of complications caused by type 2 diabetes, including cardiovascular disease, and the more recently recognized correlation with cancers of wide variety of tissues, anti-diabetic therapies are urgently needed to relieve the overwhelming and costly diabetic complications.
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