Funded Investigators (2021)
Danielle Haslam, PhD
Postdoctoral Research Fellow at Brigham and Women’s Hospital
“Multi-omic signatures of sugar and artificially-sweetened beverages and changes in body weight”
Diet and lifestyle interventions aimed to treat and prevent weight gain are difficult to adhere to due to an abundance of calories in the environment, which includes calories from sugar-sweetened beverages (SSB). We plan to utilize a precision nutrition approach to identify novel multi-omic signatures of SSB and artificially-sweetened beverage (ASB) consumption among adults through use of an established longitudinal cohort study. This project will provide critical preliminary data to demonstrate the potential for success of a planned NIH K01 submission detailing the first study to examine multi-omic signatures of SSB and ASB consumption in a randomized controlled trial.
Natalia Machado, MS, PhD
Staff Scientist, Beth Israel Deaconess Medical Center and Instructor in Neurology, Harvard Medical School
“A master switch in the regulation of body temperature and metabolic rate”
During environmental or physiological challenges, adaptive responses modulate the metabolic rate and body temperature below or above their homeostatic set-point. In this study, we will investigate the identity of preoptic neurons that regulate adaptive energy-conserving and fever responses.
Clemens Wittenbecher, PhD
Postdoctoral Fellow, Department of Nutrition at Harvard TH Chan SPH
“Metabolomics profiles’ 10-year changes linking diet, obesity and genetics to subsequent T2D risk”
Precision prevention of type 2 diabetes requires dynamic biomarkers that identify high-risk population groups and reflect the change in future disease risk in response to lifestyle modifications and weight loss. I propose using first-of-its-kind repeated metabolomics data with a 10-year lag between measurements in a type 2 diabetes case-control study in the Nurses’ Health Study to develop a metabolite score that predicts type 2 diabetes; to examine how the change in lifestyle and body weight is related to concurrent metabolite score changes and subsequent disease risk; and, to conduct comprehensive interaction analyses with the metabolite score in the Harvard cohorts and the PREDIMED-trial, with the aim to identify vulnerable population groups with the greatest benefit from lower body weight and healthier diet. I expect exciting insights into the molecular underpinnings of diabetes prevention through lifestyle modifications with high translational potential, providing strong preliminary data for my future K99/R00 and AHA and ADA career development award applications.
Hassan Dashti, PhD, RD
Postdoctoral Research Fellow, Massachusetts General Hospital
“Phenome-wide interactions between obesity genetic risk and lifestyle traits in an electronic health record biobank”
This study will test the hypothesis that phenomewide interaction scans of electronic health record biobanks will provide insights into multiple clinical phenotypes where targeting obesogenic lifestyle behaviors may attenuate obesity genetic risk.
Andrew Lutas, PhD
Instructor in Medicine, Beth Israel Deaconess Medical Center
“Peptidergic control of the motivation to eat via presynaptic modulation”
This study will determine the feasibility of recording neuropeptide-evoked intracellular signals in mice actively seeking food and whether manipulating specific intracellular signals can suppress cue-triggered overeating. This research direction may lead to new candidate pharmacological targets for the treatment of obesity
Funded Investigators (2019-2021)
Melanie Schorr Haines, MD
Assistant in Medicine, Massachusetts General Hospital
Instructor in Medicine, Harvard Medical School
“Effects of exercise on circulating myokine levels in insulin-resistant vs insulin-sensitive adults with overweight/obesity”
In response to exercise, muscle synthesizes and secretes myokines, which are an important mediator of the beneficial metabolic effects of exercise, and may therefore be potential therapeutic targets in the prevention and treatment of type 2 diabetes. We hypothesize that exercise-induced changes in circulating myokine levels will be attenuated in insulin-resistant compared to insulin-sensitive adults with overweight/obesity. Thirty subjects – 15 with insulin resistance and 15 without insulin resistance will undergo cardiopulmonary exercise testing with blood samples taken before and after exercise for serum myokine levels.
Sarah Lessard, PhD
Assistant Professor/Assistant Investigator, Joslin Diabetes Center, Inc.
“Impact of Western Diet on the molecular and physiological response to exercise”
There has been a worldwide shift toward consumption of a Western Diet characterized by high intake of processed sugars and fats. This project will use mouse models to test the hypothesis that a Western Diet can blunt health improvements that normally occur with exercise by altering the molecular signals induced in muscle with each session of acute exercise.
Dong Wang, MB, MS, ScD
Research Scientist, President and Fellows of Harvard College
“Mediterranean Diet, Gut Microbiome and Cardiac Structure and Function”
This research will test whether the gut microbiome modifies the effects of the Mediterranean diet for delaying the age-related changes in cardiac structure and function in a randomized controlled dietary trial. We will also explore the mechanisms that link the Mediterranean diet, gut microbiome, and cardiac structure and function be examining gut microbiota-linked metabolites and intestinal permeability.
Funded Investigators (2018-2019)
Amar Dhand, MD DPhil
Assistant Professor, The Brigham and Women’s Hospital, Inc.
“Study of social networks and their inter-relations with diet, physical activity, and obesity”
This is a study of social networks and obesity in individuals in two large cohort studies, Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS).
Laura E. Dichtel, MD, MHS
Instructor, Massachusetts General Hospital
“The Growth Hormone and Insulin-like Growth Factor-1 Axis in Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis”
This translational pilot study will investigate the cell-specific molecular mechanisms of GH and IGF-1 receptor density and signaling in hepatocytes and hepatic stellate cells in this disease process, which could lead to new, targeted therapies for inflammation and fibrosis in patients with NAFLD and NASH.
Jennifer Lee, PhD
Instructor, Beth Israel Deaconess Medical Center
“Molecular Basis for Enteroendocrine Cell Dysfunction in Type 2 Diabetes”
There is a major unmet need for safe and effective therapeutic modalities for the treatment of obesity and Type 2 Diabetes. Enteroendocrine cells play a critical role in regulating glucose metabolism, yet they are an undercharacterized and understudied cell target. Identifying molecular signatures that beneficially regulate enteroendocrine cell function may have clinical implications for improving glucose homeostasis in metabolic disease.
Jun Li, MD, PhD
Postdoctoral Research Fellow, Harvard T.H. Chan School of Public Health
“Chronic Inflammation and Obesity: Genetic Susceptibility and the Role of Diet”
This project will integrate novel genomics approaches with large-scale epidemiological studies, to examine the mechanistic relations between chronic inflammation with obesity and its co-morbidities, and whether dietary inflammatory potentials interact with polygenic risk in influencing long-term weight gain.
Yoav Livneh, PhD
Research Fellow, Beth Israel Deaconess Medical Center
“Convergent and divergent coding in insular cortex and amygdala across hunger and thirst”
This study will focus on insular cortex, a brain area considered important for guiding actions to address current bodily needs (such as thirst or hunger), to test whether and how it assesses current physiological need states (dehydration vs. caloric deficiency) to prioritize and guide specific actions (water-seeking when thirsty, food-seeking when hungry).
Franziska Plessow, PhD
Instructor, Massachusetts General Hospital
“Sustained oxytocin administration, cognitive control, and reward responsiveness in human obesity”
This project is a randomized, doubleblind, placebo-controlled study of obese adults to investigate the effects of 4 weeks of sustained intranasal oxytocin administration on cognitive control and reward responsiveness and their role in the beneficial effects of oxytocin on food intake and weight.
Tracey Simon, MD
Clinical Research Fellow, Massachusetts General Hospital
“Insulinogenic and Inflammatory Dietary Factors and Risk for Hepatocellular Carcinoma”
The central goal of this project is to prospectively characterize the modifiable dietary and lifestyle factors that operate through insulinogenic and inflammatory metabolic pathways to contribute to the pathogenesis of hepatocellular carcinoma (HCC), in persons with obesity and diabetes.
Linus Tsai MD, PhD
Assistant Professor, Beth Israel Deaconess Medical Center
“Role of Pars Tuberalis in Energy Homeostasis”
The overall goal of this project is to study how cells of the pars tuberalis act to affect body weight regulation and energy homeostasis.