About Our Investigations and Research 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, NAFLD/NASH, 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, GIP, and other incretin 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" incretin analogs involving leptin, GIP, GLP-1, and other incretin analogs 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.
The Mantzoros research group conducts Basic Research across a spectrum of conditions to improve understanding of human physiology, metabolic pathways, hormone responses, and more. Our projects aim to:
- Investigate the physiology of novel hormones in the regulation of energy balance in conditions of energy deprivation (e.g. anorexia nervosa, starvation, strenuous exercise) or of energy excess (obesity, diabetes, non-alcoholic fatty liver disease) in humans.
- Identify molecular pathways related to metabolic diseases in humans using both targeted and untargeted “omic” approaches and assessing their potential as prognostic markers or therapeutic tools for obesity, diabetes, NASH, and other metabolic diseases.
- Explore the role of promising new classes of anti-obesity medications (e.g. leptin, adiponectin, serotonin receptor agonists, incretins) and of nutritional interventions (e.g. walnut consumption, coffee intake, Mediterranean diet) on appetite control using neurocognitive and neuroimaging techniques and on cardiometabolic profile through hormonal, biochemical, metabolomic and lipidomic analyses.
- Perform "proof of concept studies" in mice and humans involving leptin, GLP-1, and other incretins, neuropeptide agonist administration and PPARγ selective modulators to fully elucidate their role in human physiology and disease as well as their treatment efficacy in disease states such as obesity, diabetes and NAFLD.
- Investigate the pathophysiological link between obesity and diabetes, metabolic and hormonal milieu and malignancies.
We conduct large-scale epidemiologic investigations, including cross-sectional, case control, and cohort studies, to examine:
- Obesity-associated comorbidities, including NASH
- Physiological 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 etiology, clinical manifestations, and response to bariatric surgery in patients with obesity, diabetes, NASH, and other relevant metabolic diseases.
Our clinical research studies focus on:
- 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 novel dual and triple incretin receptors agonist; in addition to lorcaserin (a specific serotonin receptor agonist) in lean and/or obese subjects.
- Nutritional epidemiology 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, and nonalcoholic steatohepatitis (NASH).