Research
Our Major Research Interests
Eating disorders and their metabolic consequences, including obesity and associated comorbidities, are the epidemics of the 21st century. Our group works hard to prevent, diagnose, treat associated disease states, to understand the mechanisms underlying these disorders and consequently develop rational novel diagnostic and therapeutic tools for these conditions. More specifically, our main focuses are:
- Obesity and its consequences, including diabetes, cardiovascular disease and malignancies
- Nutrition and Metabolism
- Molecular pathogenesis of obesity, insulin resistance, and associated comorbidities, including cancer, cardiovascular disease, insulin resistance and type 2 diabetes
- Molecular biology, physiology, and pathophysiology of adipokines in animals and humans
- The role of adipokines in diabetes, cardiovascular disease and malignancies
- Clinical epidemiology, clinical research and interventional studies in humans
- Developing new diagnostic and therapeutic tools for the above disease states
Basic Research Studies
Our basic research studies focus on physiological and pathophysiological regulation of novel molecules important in energy homeostasis, diabetes, and obesity, as well as complications of the latter including cardiovascular disease and malignancies. We utilize a wide range of research methods including genomics-bioinformatics, molecular biology, as well as animal physiology studies to answer important questions in the area of obesity, insulin resistance, and their consequences including diabetes, cardiovascular disease, and malignancies. Our ultimate goal is to develop novel diagnostic and therapeutic strategies by better-understanding and exploiting underlying mechanisms.
Epidemiology
We conduct and participate in large scale epidemiological investigations, including cross-sectional, cohort, and case control studies, in collaboration with members of the Environmental Health, Nutrition, and Epidemiology Departments of the Harvard School of Public Health.
Our research efforts have expanded to studying non-modifiable disease determinants including certain single nucleotide polymorphisms as well as modifiable determinants such as diet and exercise, as predictors of adipokine concentrations and/or disease states in humans.
We have performed the first case-control and prospective cohort studies demonstrating that adiponectin is a missing link between obesity/insulin resistance and common malignancies associated with obesity including endometrial, breast, prostate, renal, and colon cancers. Ongoing studies are investigating the underlying mechanisms and exploring the potential role of adiponectin as a diagnostic and therapeutic agent in these conditions.
The above basic research and epidemiology studies have provided important new information and have advanced our knowledge of human physiology and pathophysiology. The hope is that these advances will ultimately lead to therapeutic breakthroughs.
Clinical Interventional Studies
Our interventional studies in humans range from early phase pharmacokinetic and small scale, investigator-initiated "proof of concept” studies, to medium, and large-scale double blind placebo-controlled clinical trials, which, if positive, are later expanded into multi-center clinical trials.
Our group was the first to complete pharmacokinetic studies of leptin in humans. We were the first to conclusively demonstrate, utilizing “proof of concept” studies involving leptin administration, the role of leptin in regulating the neuroendocrine response to energy deprivation in humans. We were also the first to demonstrate that low leptin levels are intimately linked with neuroendocrine abnormalities observed in hypothalamic amenorrhea and anorexia nervosa. Further, we demonstrated that administration of leptin, in replacement doses, corrects the neuroendocrine and reproductive abnormalities and improves markers of bone density in strenuously exercising women athletes with hypothalamic amenorrhea. Currently, we are exploring further the role of leptin in the physiology, pathophysiology, and potential treatment of several disease states, including obesity.
Examples of our current studies are presented in the projects section.
Clinical Innovations
We have previously published and patented:
- Methods for treating intestinal inflammation or ghrelin-mediated inflammation by inhibiting the activity of ghrelin or its receptor.
- Methods for identifying ghrelin antagonists and ghrelin receptor antagonists.
- Methods for diagnosing and treating malignancies using adiponectin.
- Adiponectin as a diagnostic test for epithelial cancers, including endometrial, based on serum levels of adiponectin and associated therapeutic compounds.
Our work, funded by the NIH, the ADA, HMS, Foundations, and Pharmaceutical Industry, has resulted in over 250 original publications in medicine, more than 50 collaborative papers in the context of the Look AHEAD Study, over 100 reviews/chapters in textbooks, and over 11,000 citations. Group members have been honored with prestigious awards at National/International meetings.
