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Projects

Project Goals

The Mantzoros research group conducts independent investigations and collaborates on several projects with experts from national and international institutions. Our projects aim to:

  • Investigate the etiology, underlying molecular mechanisms and pathophysiological links between obesity/adipose tissue, diabetes, cardiovascular disease, and malignancies.

  • Explore the role of promising new classes of anti-obesity medications including leptin and other peptides such as adiponectin, serotonin receptor agonists, and incretins such as GLP-1 analogues in the treatment of obesity and the metabolic syndrome (insulin resistance, diabetes, hypertension, hyperlipidemia).

  • Investigate the roles of leptin and neuropeptides in obesity as well as the mechanisms underlying their roles.

  • Investigate new molecular targets for the treatment of obesity, diabetes, cardiovascular disease, and endocrine malignancies.

  • Perform "proof of concept studies" involving leptin, GLP-1, and neuropeptide agonist administration in humans to fully elucidate their role in human physiology and disease. 

Specific examples of ongoing research projects are outlined below.

Basic Research

The Mantzoros research group utilizes genomics-bioinformatics, molecular biology, and human investigation tools to discover and study novel molecules, especially adipokines, important in the pathogenesis of diabetes, obesity, and associated disease states, including cardiovascular disease and malignancies. Our animal physiology and molecular biology studies specifically examine:

  • The role of hypothalamic neuropeptides and adipocyte secreted hormones in energy homeostasis/ obesity and insulin resistance/ diabetes.

  • The role of new therapeutic agents important in the treatment of eating disorders and the metabolic syndrome.

  • The role of adiponectin in the diagnosis and treatment of several obesity-related malignancies

  • Leptin and adipokine signaling in vitro, ex vivo, and in vivo (rodents and humans).

  • The biology of molecules upstream of adiponectin, such as PPAR-γ and PGC-1α, as well as other related molecules including irisin. 

Epidemiology

We conduct large-scale epidemiologic investigations, including cross-sectional, case control, and cohort studies, to examine: 

  • Obesity associated malignancies.

  • Psychological mediators of risk and predictors of diabetes and cardiovascular disease in diabetic individuals in the context of the Nurses Health Study and the Health Professionals Study.

  • The Metabolic syndrome in HIV-positive patients. 

  • The etiology, clinical manifestations, and response to bariatric surgery in obese patients.

  • Dietary patterns that may mediate the effect of early life adversities and/or post-traumatic stress disorder on central obesity and metabolic syndrome development.

Clinical Research

Our clinical research studies focus on:

  • The etiology and management of the metabolic syndrome in HIV-positive patients. 

  • The physiology of leptin in lean and obese individuals and the associations between leptin levels, pulsatile secretion of leptin, and neuroendocrine and immune function in humans.

  • Randomized, double-blind, placebo-controlled trials to investigate the effect of leptin treatment in several disease states.

  • Randomized, double-blind, placebo-controlled trials investigating the effects of liraglutide (a GLP-1 analogue) and locaserin (a specific serotonin receptor agonist) in lean and/or obese subjects.

  • Nutrition studies as well as controlled, randomized meal replacement weight loss studies.

  • Randomized clinical trials in obese patients with diabetes including the Look AHEAD study, i.e. a study of health outcomes in response to weight-loss. In a national multi-center clinical trial, the Look AHEAD study, we examine the long-term effects of an intensive lifestyle intervention program designed to achieve and maintain weight loss by decreasing caloric intake and increasing physical activity in overweight volunteers with type 2 diabetes.

  • Interventional placebo-controlled trials for the treatment of diabetes and obesity.

 

 

Contact Information

Division Of Endocrinology, Diabetes, and Metabolism
Beth Israel Deaconess Medical Center
Feldberg 875
330 Brookline Ave
Boston, MA 02215
617-667-8630
617-667-8634