Learn more about the diverse backgrounds and research interests of our faculty!
Dr. Apovian’s ongoing research includes several areas of weight loss, weight maintenance, and the molecular effects of weight change. Her current research includes:
- determining the effects of weight loss on endothelial cell function, adipose cell metabolism and inflammation (in conjunction with the Department of Cardiology)
- researching the bariatric surgery population in the Nutrition and Weight Management Center
- studying the quality of life before and after weight loss surgery (in collaboration with Beth Israel Deaconess Medical Center)
- researching the effects of bariatric surgery on adipose tissue and the effects of a novel meal replacement program on body composition
- studying novel pharmacotherapeutic antiobesity agents, such as leptin
- a study quantifying the relative inflammatory burden and cytokine expression of adipose cells in human fat stores in obese participants after weight loss treatment with low-fat vs. low-carbohydrate diets
Dr. Bandini‘s research interests include:
- childhood Obesity
- energy expenditure in children
- health promotion
- dietary intake and physical activity in children with developmental disabilities
Dr. Cook conducts research on food insecurity and energy insecurity, and their impacts on the health of young low-income children and their mothers. Dr. Cook is a Senior Research Scientist with Children’s HealthWatch, and is project evaluator for several programs within the Department of Pediatrics’ Nutrition and Fitness for Life (NFL) program, including its FANtastic Kids intervention to reduce obesity among elementary-school-age children. He also consults with America’s Second Harvest, the Nation’s Foodbank Network and chairs the Technical Advisory Group for its national research studies. Current research also includes:
- Assessment of affordability and accessibility of healthy foods in low-income neighborhoods of Boston and Philadelphia
- viable approaches to food systems reform
The main goal of the Corkey laboratory is to determine how fuels generate the signals to communicate among different organs in the body to modulate hormone and adipokine exocytosis, electrical activity, metabolism and gene expression. Work focuses on the influence of metabolites and mitochondrial energy state on intracellular signal transduction in adipocytes, pancreatic ß-cells, liver and human fibroblasts. Recent research has examined
- ion handling
- the signaling consequences of cellular energy state
- the influence of fatty acids on protein kinases
- the role of fatty acids and long acyl CoA on signal transduction
Unique resources of the laboratory include imaging, fluorescence and amperometric techniques to measure responsiveness of living cells to various treatments and stimuli. Collaborations include: the BioCurrents Laboratory of the Marine Biological Institute, the Karolinska Institute, the Universities of Chicago, Montreal and Pennsylvania, and the Hamner Institutes for Health Sciences.
Dr. Deeney‘s research is designed to discern the nutrient-derived metabolic signals leading to glucose-and fatty acid-induced insulin exocytosis from the pancreatic ß-cell. FA acutely stimulates glucose-induced insulin secretion (GSIS) while chronic exposure to elevated FA and glucose can result in glucolipotoxicity (GLT) with basal hypersecretion and inhibition of GSIS. Despite the adverse effects of chronic exposure, FA is known to be required for normal exocytosis from the ß-cell. Current research includes:
- Deciphering the dual effects of FA on GSIS to lead to the possible development of therapies that would reduce the inhibitory effects while sparing the stimulatory effects of FA on the ß-cell.
- Identifying the lipids or lipid classes involved in enhancing and suppressing GSIS and assessing their effects on lipid-modulated or modulating proteins.
The overall goal of the Denis lab is to understand the fundamental mechanisms of transcriptional control of growth and development, and particularly, how chromatin-based disruptions of the eukaryotic cell cycle can lead to malignancy. Research techniques utilized in the lab range from basic molecular biology techniques, to proteomic analyses, to transgenic and knockout mouse models. Results to date have broad significance for our understanding of:
- Adaptive immunity
- B cell proliferation
- Non-Hodgkin’s lymphoma (NHL)
The overall focus of the Farmer laboratory is to understand the molecular mechanisms controlling the formation and function of adipocytes with a focus on identifying the signaling pathways and transcription factors that regulate adipogenesis. Current projects are investigating:
- The role of PPARgamma (peroxisome proliferator-activated receptor gamma) and the C/EBPs (CCAAT/enhancer binding proteins) in regulating the sequential expression of the adipogenic factors that control the differentiation of preadipocytes into adipocytes and expression of genes that control various adipocyte functions including insulin-dependent glucose uptake and production of adiponectin.
- The mechanisms by which the adipocyte responds to changes in energy balance by focusing on role of the NAD-dependent deacetylase, SIRT1, and the hypoxia-induced factor-1 alpha (HIF-1alpha) in regulating adipocyte gene expression.
Adipocytes are highly specialized cells that store and release energy according to the needs of the organism. They are also now recognized as endocrine cells that synthesis and release hormones in proportion to energy storage and changes in nutritional status (e.g. obesity/overfeeding, fasting and refeeding). Research in the Fried lab focuses on the mechanism regulating adipocyte metabolism and endocrine function. The long-term goal of the lab is to understand why obesity and an upper body fat distribution are is associated with metabolic abnormalities such as type 2 diabetes and atherosclerosis, and why a lower body adipose tissue (femoral-gluteal) typical of women is actually protective. Recent work addresses:
- The regulation of leptin, an adipocyte hormone that regulates metabolism and appetite and is centrally involved in the regulation of body weight.
- The regulation of leptin translation
- Understanding the molecular basis of sex and depot differences in adipocyte and adipose tissue function by using microarrays to identify the primary targets of glucocorticoid in human adipose tissues in vivo and in vitro, and assessing the functional roles of these genes.
- Studies of estrogen action in human adipose tissue
Davidson Hamer is a Professor of International Health and Medicine at the Boston University School of Public Health and School of Medicine. He has twenty years of field experience in neonatal and child survival research including studies of micronutrient interventions, maternal and neonatal health, malaria, pneumonia, and diarrheal diseases. Major current projects include:
- A large neonatal survival study, community-based interventions to reduce neonatal and under-5 child morbidity from common diseases
- Determining the role of specific micronutrients in reducing the burden of disease due to malaria in pregnancy
- An evaluation of the association of vitamin D deficiency with pneumonia in Ecuadorian children.
Dr. Hamilton’s laboratory is developing and applying novel physical approaches to study of obesity, metabolic syndrome, and cardiovascular disease. 13C NMR methods pioneered in his laboratory have been used to describe the interactions of fatty acids and drugs with binding sites on albumin. Current studies extend from animal model systems (mouse and rabbit) to humans and emphasizes the interactions of different disciplines on translation of basic biophysics to human disease aspects:
- Correlating important details predicted by NMR with recent x-ray crystal structure.
- New fluorescence approaches have been developed to characterize the diffusion of fatty acids into adipocytes and evaluate the effects of drugs and inhibitors on fatty acid uptake.
- The application of magnetic resonance imaging (MRI) to examine fat tissue and atherosclerosis.
Our study of subjects with metabolic syndrome and obesity explores the hypothesis that a unifying feature of metabolic syndrome is enhanced deposition of lipids throughout the body outside of the normal adipose stores. MR imaging will identify and quantify site-specific abnormalities in obese patients including cardiac functions.
Dr. Holick and his team of researchers continue to be leaders in the field of vitamin D, osteoporosis, metabolic bone disease, psoriasis and hair research. Dr. Holick’s work explores the nature of vitamin D deficiency and concludes it to be one of the most commonly unrecognized medical conditions, a condition that leaves millions at risk of developing not only osteoporosis and fractures but also numerous serious and often fatal diseases, including several common cancers, autoimmune diseases, infectious diseases and heart disease.
Because the skin is an important source of vitamin D, a human skin equivalent and a liposomal model have been developed to mimic the photoproduction of vitamin D in human skin. Using these models systems, researchers demonstrated that during exposure to solar simulated-sunlight, a unique membrane-associated mechanism stabilizes the previtamin D3 in a cis,cis-conformation and results in its rapid conversion to vitamin D3. It has now been demonstrated that human skin also produces several photoproducts including tachysterol and lumisterol, which may have important biologic functions in the skin.
Dr. Holick has initiated a program to evaluate the effect of vitamin D deficiency in advancing colon tumor growth.
Dr. Istfan is a clinical endocrinologist whose research is translational in nature. His research interests include the following:
- Regulation of cell proliferation and the effects of polyunsaturated fatty acids on cancer and metabolic outcomes
- Nutrition and cancer
- Insulin resistance in obesity
- Mechanisms of cardiovascular disease in obesity
- Racial differences in metabolic disorders
Diabetes mellitus represents one of the major health threats to modern civilization and its worldwide prevalence is increasing at an alarming rate. In diabetes, insulin cannot stimulate glucose entry into the cell, as it does in normal individuals. As a result, extra glucose stays in the blood and causes multiple health problems. The main focus of the Kandror lab is insulin-regulated glucose transport, as it is the major molecular defect in diabetes. Current studies include:
- Determining the regulation of exocytosis of synaptic vesicles in neurons, insulin-containing granules in the pancreas, water channel-containing vesicles in the kidney, etc., which is example of a widely spread type of the biological regulation.
- Examining the signal transduction pathway that connects the insulin receptor in the plasma membrane and intracellular Glut4-vesicles. Second, the cell biology (i.e. the protein composition, biogenesis, intracellular trafficking) of Glut4-vesicles may be impaired.
- Using the wide arsenal of modern techniques that include molecular biological methods, protein biochemistry, subcellular fractionation, microscopy and in vivo studies.
The primary goal of the Layne laboratory is to identify novel pathways that control fibroproliferation with the goal of developing therapeutic inhibitors. Current research interests include:
- Defining the pathways that control vascular adventitial remodeling
- Inhibiting organ fibrosis through targeting Aortic carboxypeptidase-like Protein (ACLP), a secreted, collagen-binding protein that enhances fibrosis and myofibroblast differentiation through mechanisms that involve stimulating the transforming growth factor ß (TGFß) receptor signaling complex and controlling mechanical signaling and ECM remodeling
- Developing systems to understand the stomal reaction in breast cancer (in collaboration with the Kirsch lab).
- Uncovering new mechanisms that control adipose tissue fibrosis (collaboration with Farmer lab).
Dr. Lenders has been the medical director of the NFL Program (Pediatrics – Nutrition & Fitness for Life) since 2003. She also heads the Pediatric Nutrition Support Services at Boston Medical Center, and she serves as attending physician for the Nutrition Support Team at the Children’s Hospital of Boston.
Dr. Lenders is a former family practitioner with a master’s degree in tropical medicine, who graduated with honors from the State University of Liege, Belgium. She spent several months in the Congo with Médecins sans Frontières and three years in Bangladesh at the International Center of Diarrheal Diseases and Research.
Her current research interests include the relationship of selective dietary components and medications to weight gain and obesity-related conditions.
Dr. Moore directs the Framingham Children’s Study, which has shown how lifestyle factors starting early in life relate to the development of obesity during childhood and later cardiovascular risk. Much of Dr. Moore’s recent research has dealt with key analytic questions related to obesity and diabetes:
- The effect of obesity and diabetes, including gestational diabetes, on pregnancy outcome
- Effects of sustained and non-sustained weight loss on the risk of adult-onset diabetes, hypertension, and cardiovascular disease
- Effects of weight and weight gain on cancer risk (colon, breast, prostate, lung)
- The causes and consequences of obesity in childhood
- The effects of anemia on the risk of heart failure and cardiovascular disease
Dr. Pearce has received national and international recognition for her research, has published many original articles, reviews, and editorials, is a sought-after lecturer, and has received multiple awards and honors. Her main areas of clinical and research expertise are:
- Dietary iodine sufficiency in the U.S.
- Thyroid function in pregnancy
- Effects of environmental perchlorate exposure on the thyroid
- Cardiovascular effects of subclinical thyroid dysfunction and thyroid disease
The Perissi lab investigates how different inputs are integrated and translated in fine-tuning of transcriptional regulation via the action of signal transduction pathways, ubiquitin conjugating machineries and chromatin remodeling enzymes.
Techniques used include:
- in vitro biochemical and cellular experiments
- in vivo modeling using tissue-specific mouse models
- high throughput next generation sequencing approaches
Current research is focused on:
- Understanding how different components of the NCoR/SMRT corepressor complex contribute to broadly regulate the cellular responses to external stimuli
- Understanding changes in bioenergetic needs through transcriptional and non-transcriptional functions
The modern Western diet coupled with a sedentary lifestyle has led to an epidemic of obesity, a consequence of which is a dramatic rise in the incidence of type II diabetes mellitus, a malfunction in insulin-regulated metabolism. At the cellular level, type II diabetes is characterized by failure of insulin to act in liver, muscle and fat. The Pilch lab studies aspects of insulin signaling and action in the latter two tissues. Current studies seek to understand pathways involved in pathophysiological states such as diabetes:
- Insulin resistance in muscle (and fat) derives from the failure of insulin to activate the tissue-specific glucose transporter GLUT4 and involve the physiological role of cell surface (plasma membrane) micro-domains called caveolae that are particularly abundant in these tissues.
- Continued study on other aspects of adipocyte and muscle cell biology, as well as the effect of exercise to understand the interplay between glucose and fat metabolism
- The interplay between adipocytes and muscle required for overall metabolic homeostasis
Dr. Quatromoni holds positions in the Nutrition, Department of Health Sciences, College of Health and Rehabilitation Sciences at the Sargent College of Boston University and the Department of Epidemiology, and Department of Social & Behavioral Sciences at the Boston University School of Public Health. Research interests include:
- School-based health promotion and nutrition education
- Child, adolescent, and adult obesity
- Diet and chronic disease, specifically cardiovascular disease and metabolic disease
- Sports nutrition
- Eating disorders prevention and treatment
- Dietary assessment
Dr. Ramachandran is a senior investigator at The Framingham Heart Study, which is a long-standing ongoing longitudinal epidemiological cohort study. Over the years, careful monitoring of the Framingham Study population has led to:
- The identification of major CVD risk factors, as well as valuable information on the effects of these factors such as blood pressure, blood triglyceride and cholesterol levels, age, gender, and psychosocial issues.
- Risk factors for other physiological conditions such as dementia have been and continue to be investigated.
- In addition, the relationships between physical traits and genetic patterns are being studied.
Dr. Ray’s research interests include:
- The structural biology of the vitamin D and estrogen endocrine systems
- Structure of hormone receptors, structure-activity relationship studies
- Proteomic/combinatorial approaches to develop drugs for cancers of prostate and breast
- Novel approaches to site-specific delivery of cancer drugs.
Dr. Ruderman’s research focus is on the effects of insulin, exercise, and fuels on cellular metabolism, signal transduction and most recently, gene expression. Reserach over the past 10 years includes:
- Examining malonyl CoA fuel sensing and signaling mechanism and its regulation by AMPK.
- Proposed that dysregulation of this mechanism, leading to increases in fatty acid esterification and/or the generation of reactive O2 species, plays a causal role in the pathogenesis of many forms of insulin resistance in skeletal muscle and the early endothelial cell damage that antedates atherosclerosis in diabetes.
- Examines the notion that activation of AMPK prevents this dysregulation and, perhaps independently, B-mediated gene expression) in skeletal muscle, endothelial cells, and adipocytes.
- The techniques employed by the Ruderman laboratory include reporter gene assays, adenoviral gene transfer (cultured vascular cells), immunofluorescence microscopy, protein separation, enzyme analysis, and metabolite determination by spectrophotometric and chromatographic methods.
- The models used include incubated tissues, cultured cells, intact rodents and, in some collaborative efforts, humans.
Mitochondrial oxidative damage plays a key role in degeneration, aging and metabolic diseases. The goal of the Shirihai lab (currently located at UCLA) is to determine how damage is prevented or contained, how dysfunctional mitochondria are recognized and removed, and how mitochondrial networks participate in these processes. Current research includes two disease models in which oxidative damage to mitochondria play a key role in the development of pathology:
- In diabetes, nutrient-induced oxidative damage has been shown to be a major mediator of endocrine dysfunction and β-cell loss.
- In bone marrow, oxidative damage induced by iron and hemeintermediates, leads to the development of sideroblastic anemia and myelodysplastic syndrome.
By tagging and tracking individual mitochondria in intact β-cells the lab discovered the existence of a quality control mechanism that relies on both fusion and fission.
Following mitochondrial fission some daughter units depolarize. These units display a lower likelihood for subsequent fusion and are apparent targets of autophagy. Moreover, this model predicts that the inhibition of mitochondrial dynamics (MtDy) by Gluco-lipo-toxicity (GLT) may have a cumulative effect and result in an increased portion of dysfunctional units over time.
Dr. Tornheim has spent year studying the spontaneous oscillatory behavior of glycolysis in muscle extracts. These oscillations involve the regulatory properties of the key control enzyme, phosphofructokinase, which was therefore the object of related kinetic studies. Current research in the lab includes:
- Testing the hypothesis that such oscillatory behavior of glycolysis and the ATP/ADP ratio underlies glucose-stimulated oscillations in intracellular free Ca2+ and insulin secretion in pancreatic islets. Such oscillations can increase the potency of insulin, and loss or derangement of these oscillations may contribute to the development of type 2 diabetes.
- Determining fuel metabolism and AMP-activated protein kinase in vascular tissue, muscle and other tissues.
In collaboration with other members of the Diabetes and Metabolism Unit, research on the metabolic changes that may be responsible for the frequently occurring vascular complications of diabetes.
The Zhang lab focuses on how insulin signaling networks and innate immunity regulate metabolic functions. Current research in the lab includes:
- Studying a protein called CDP138 and the signaling networks related to glucose and lipid metabolism.
- Exploring the role of neutrophils and neutrophil elastase in the development of obesity-related adipose inflammation, insulin resistance, and cardiovascular dysfunction.