Research Description
Obesity and diabetes have reached alarming proportions worldwide. There is extensive evidence pointing to the genetic causes of these diseases, but pinpointing which and how genes cause them, and advancing their treatment has been met with little success. Introduction of human mutations in the protein ankyrin-2 (AnkB) (found in patients with diabetes and heart disease) in mice results in abnormalities in the pancreas, gain weight more easily, and eventually become obese and insulin resistant. Mice also become significantly fatter and reach a pre-diabetic state when AnkB is eliminated from fat cells only. At the cellular level, deficiencies in AnkB cause defects in the uptake of glucose by fat and muscles. Based on these findings, the Lorenzo lab believes that AnkB plays essential roles in the normal functioning of fat and muscle tissue, and their deficiencies lead to glucose dysregulation, obesity, and T2D. Therefore, through animal and cellular studies, the Lorenzo lab will decipher how AnkB ensures proper functioning of fat and muscle tissues, and why their mutations cause obesity and diabetes in humans. This knowledge can lead to personalized intervention for millions of people affected by these mutations.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?Sub-optimal metabolism of nutrients can lead to sustain weight gain even in conditions of normal diet and active life styles. Likewise, over-consumption of certain nutrients can increase predisposition to obesity and diabetes. This project will investigate novel aspects of the molecular mechanism underlying glucose handling by fat and muscle tissues. In addition, we will study the molecular mechanisms involved in the deficient metabolism and peripheral tissue handling of branched chain amino acids, which high circulation levels in the blood has become one of the most faithful predictors of diabetes. A more accurate understanding of these cellular mechanisms will result in refined therapeutic discovery and prevention strategies.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?Defective handling of glucose by adipose tissue and skeletal muscle is the hallmark of diabetes. Although we have advanced our molecular understanding of how these tissues uptake and handle glucose, the picture is incomplete. In this project we will investigate how dysregulation of the protein ankyrin-B, a novel molecule involved in the cellular uptake of glucose, affects systemic glucose and branched chain amino acid levels that may lead to insulin resistance. Mutations in ankyrin-B have been associated with diabetes and heart disease in patients. Therefore, our research will be directly relevant not only to patients who may suffer from diabetes and/or are obese because of a genetic mutation in the gene encoding ankyrin-B, but it will also advance our cellular understanding and potential therapeutic management of systemic glucose.
Why important for you, personally, to become involved in diabetes research? What role will this award play?As a basic research scientist my goal is to discover what goes awry at the cellular and physiological levels during disease. In turn, I hope that these discoveries get translated into preventive practices, precise diagnoses, and effective therapeutic interventions. I am personally interested in diabetes research because of the heightened urgency to prevent and effectively treat this disease, which has reached epidemic levels with devastating health effects. One of the most alarming statistics is the growing incidence of diabetes in vulnerable populations, such as children and certain ethnic communities. As someone with roots in some of the communities most affected by the diabetes epidemic and who has witnessed firsthand its detrimental effects, I’m personally motivated to helping advance it prevention and treatment. This award will allow my laboratory to advance those goals.
In what direction do you see the future of diabetes research going?Diabetes is a complex disease which encompasses diverse genetic and environmental components. In addition, diabetes can originate from the dysregulation of one of several organs, which in turn can affect other organs and systems. Thus, both treating and learning about diabetes requires that we take into consideration its multi-organ complexity. For example, the brain has central relevance to diabetes not only because it regulates important processes such as appetite, which is directly linked to pre-diabetic states such as obesity, but also because diabetes itself can lead to decline in cognitive function and other brain health issues. In addition to diabetes research, I also study the mechanisms of neurodevelopmental and neurodegenerative diseases. As a future path of my research I foresee the integration of these two lines of research to both better understand how diabetes affects brain function and how brain dysfunction may be linked to obesity and diabetes.