Current Research and Scholarly Interests
The ANNES LABORATORY of Molecular Endocrinology: Leveraging Chemical Biology to Treat Endocrine Disorders
The prevalence of diabetes is increasing at a staggering rate. By the year 2050 an astounding 25% of Americans will be diabetic. The goal of my research is to uncover therapeutic strategies to stymie the ensuing diabetes epidemic. To achieve this goal we have developed a variety of innovate experimental approaches to uncover novel approaches to curing diabetes.
(1) Beta-Cell Regeneration: Diabetes results from either an absolute or relative deficiency in insulin production. Our therapeutic strategy is to stimulate the regeneration of insulin-producing beta-cells to enhance an individual’s insulin secretion capacity. We have developed a unique high-throughput chemical screening platform which we use to identify small molecules that promote beta-cell growth. This work has led to the identification of key molecular pathways (therapeutic targets) and candidate drugs that promote the growth and regeneration of islet beta-cells. Our goal is to utilize these discoveries to treat and prevent diabetes.
(2) The Metabolic Syndrome: A major cause of the diabetes epidemic is the rise in obesity which leads to a cluster of diabetes- and cardiovascular disease-related metabolic abnormalities that shorten life expectancy. These physiologic aberrations are collectively termed the Metabolic Syndrome (MS). My laboratory has developed an original in vivo screening platform t to identify novel hormones that influence the behaviors (excess caloric consumption, deficient exercise and disrupted sleep-wake cycles) and the metabolic abnormalities caused by obesity. We aim to manipulate these hormone levels to prevent the development and detrimental consequences of the MS.
HEREDIATY PARAGAGLIOMA SYNDROME
The Hereditary Paraganglioma Syndrome (hPGL) is a rare genetic cancer syndrome that is most commonly caused by a defect in mitochondrial metabolism. Our goal is to understand how altered cellular metabolism leads to the development of cancer. Although hPGL is uncommon, it serves as an excellent model for the abnormal metabolic behavior displayed by nearly all cancers. Our goal is to develop novel therapeutic strategies that target the abnormal behavior of cancer cells. In the laboratory we have developed hPGL mouse models and use high throughput chemical screening to identify the therapeutic susceptibilities that result from the abnormal metabolic behavior of cancer cells.
As a physician scientist trained in clinical genetics I have developed expertise in hereditary endocrine disorders and devoted my efforts to treating families affected by the hPGL syndrome. By leveraging our laboratory expertise in the hPGL syndrome, our care for individuals who have inherited the hPGL syndrome is at the forefront of medicine. Our goal is to translate our laboratory discoveries to the treatment of affected families.