- Mahua Choudhury
- Associate Professor of Pharmaceutical Sciences
- Prediction of disease risk
- Genes and the environment
Metabolic Complication Project
Our project is focused on the metabolic complications especially obesity. The rising prevalence of obesity worldwide presents a growing medical concern due to the many severe complications associated with it, with diabetes being the most common. It is estimated that about 6% of the US adult population suffers from type 2 diabetes and that more than 300 million individuals worldwide will be affected by 2020. Recently, emerging field of research raises the possibility that the aberrant epigenetic alterations might be of central regulator in metabolic complications. Acetylation has emerged as an important mechanism for controlling metabolism of a broad array of metabolic fuels. Acetylation regulates many enzymes in key pathways including TCA cycle, gluconeogenesis, and beta oxidation in yeast and human liver. This post-translational modification is governed, in part, by sirtuins, class III NAD+-dependent deacetylases (HDACs) that regulate lipid and glucose metabolism in liver during fasting and aging. SIRT3, a mitochondrial sirtuin, appears to be the primary mediator of mitochondrial acetylation, since no significant changes in acetylation status are detectable in mice lacking SIRT4 and SIRT5. Compared to caloric restriction, relatively little is known about the role of sirtuins and acetylation under conditions of caloric excess. We are examining whether rescuing SIRT3 can modify specific end points in diabetes and fatty liver, which may lead to understanding whether SIRT3 specific activators (currently in development) can be used as a pharmaceutical target.
Three decades of intensive research have yielded an impressive body of scientific knowledge about the genetic and cellular mechanisms of Type 1 Diabetes, Type 2 Diabetes, and Obesity. However, despite our increased understanding of these critical areas, these diseases are in rising worldwide. This increase is primarily due to a lack of focus on prevention. Management of diabetes represents an enormous challenge for health systems, and these systems are burdened with the task of delivering quality care to patients in all stages of the disease. The increased number of diabetic and obese people, the lack of access to screening, and the expense of appropriate therapy argue strongly for a greater focus on preventive strategies. But what is the best approach to preventing diabetes and obesity? The answer is –discovering the biomarkers that indicate the susceptibility of developing the disease. These are complex diseases that are harmful to human health and quality of life. Most of the existing biomarkers are used to measure the phenotype after disease onset and damage. At this point there is no effective biomarker to predict the threat of diabetes and obesity. Therefore, novel, early biomarkers are needed to facilitate the development of preventive interventions.
Pregnancy Complication Project
The maternal epigenome has a unique history that may be useful to interrogate in order to understand her susceptibility for pregnancy-associated diseases, such as pre-eclampsia. Thus, this unconventional approach could be used eventually to diagnose and therefore decrease the mortality rate associated with this disorder by predicting which pregnancies may be more susceptible to pre-eclampsia. In the long run, identifying these modifications could provide new drug targets or at the very least identify those at high risk for the disease in early pregnancy by properly predicting maternal risk before it emerges as a life-threatening outcome for mother and her fetus. Our idea is the novel use of epigenetics (DNA methylation, microRNA, histone modifications) as an early step towards diminishing mortality in women and babies at high risk with pregnancy disorders.