Overview The MGH Program in Nutritional Metabolism was formed in 2002 under the Direction of Dr. Steven Grinspoon, a recognized expert in the nutritional regulation of pituitary function and the metabolic consequences of obesity and fat redistribution. The Program in Nutritional Metabolism, with 8 faculty members, three current fellowship trainees, and a staff of 10 is located in 2800 square feet of newly renovated office space in Charles River Park, adjacent to the Mass General Hospital. The goal of this multidisciplinary program is to study hormonal function, nutrient trafficking, and the metabolic consequences of fat redistribution in a broad number of disease conditions, including undernutrition, obesity and acquired lipodystrophy, for example among HIV-infected patients and children. Faculty members, representing a broad array of interests including neuroendocrinology, pediatric endocrinology, nutrition and radiology, utilize state of the art techniques including insulin clamp, positron emission tomography (PET), magnetic resonance spectroscopy and K-40 isotope studies to determine metabolic function and body composition. Recent studies have investigated the use of a novel hypothalamic peptide to selectively reduce visceral fat in central obesity and a strategy to block inflammation in obesity with TNF-alpha antagonism. Among children with obesity, the relationship of mitochondrial function to insulin resistance is being studied. A major investigative focus on women has permitted the study of the effects of undernutrition on androgen metabolism and the novel use of testosterone in this population. NIH research grants to faculty have permitted a number of noteworthy accomplishments of Program staff, which include, among others:
Dr. Steven Grinspoon, Program Director, is a Professor of Medicine at Harvard Medical School, and a member of the American Society of Clinical Investigation and the Association of American Physicians. He was named Outstanding Investigator of 2005 by the American Federation of Medical Research. Dr. Grinspoon is a recognized expert in the nutritional regulation of pituitary function. His work encompasses a broad focus including the mechanism by which fat regulates neuroendocrine function, the mechanisms of insulin resistance in fat redistribution and acquired lipodystrophy and the role of altered nutrient trafficking in visceral obesity. Dr. Grinspoon was one of the first to recognize the endocrine abnormalities associated with nutritional disturbances in HIV-infected patients and has served to Chair the Department of Health and Human Services Working Group on HIV and Wasting as well as on the World Health Organization, Technical Advisory Group on Nutrition and HIV/AIDS. He Co-Chaired the Research Affairs Committee for the Endocrine Society and Directed the Endocrine Society’s Clinical Investigators Workshop. He has served as the Pfizer Visiting Professor at University of California at Davis and is also the Neuroendocrine Center Clinical Director. Most recently he chaired the AHA State of the Science Conference on Cardiovascular Disease in HIV. Current research focuses on blocking TNF in obesity and use of hypothalamic peptides, including GHRH, to selectively reduce visceral fat. His efforts led to the FDA approval in November 2010 of GHRH as the first therapy to reduce visceral fat in HIV lipodystrophy.
Sara Dolan-Looby,Ph.D, ANP-BC, received her BSN from the University of Vermont, her MSN from the MGH Institute of Health Professions, and completed her Ph.D. at Boston College in 2008. For the past 10 years, Dr. Looby has established a program of research investigating the metabolic complications of HIV among women, specifically cardiovascular disease, reduced bone density, and androgen deficiency in this population. She has published extensively in this area, and was recently awarded a K23 award to investigate the metabolic and psychological manifestations experienced by perimenopausal women with HIV. Her second project funded by the Harvard CFAR is investigating CVD risk, specifically alterations in inflammatory markers and adipokines, and their relationship to body composition among perimenopausal women with HIV. Dr. Looby lectures extensively on HIV infection in women, and is a recognized leader in this field. She is also a volunteer community educator at several AIDS service organizations throughout Massachusetts.
Meghan Feldpausch A.N.P, received her MSN from the MGH Institute of Health Professions. She is working on two studies evaluating the physiological effects of GHRH 1-44 in HIV and obesity.
Katie Fitch, A.N.P. received her BA from the University of Washington and her MSN from the MGH Institute of Health Professions. Ms Fitch has conducted several studies focusing on the assessment of metabolic complications in HIV. Most recently she has completed a study evaluating lifestyle modification and metformin among HIV-infected subjects with the metabolic syndrome and she has recently published the observation that after 1 year of treatment with lifestyle modification and/or metformin, metformin had a significant effect to halt the progression of coronary artery calcification among the participants randomized to metformin. She is currently performing a study evaluating eplerenone, a mineralocorticoid receptor blocker, among HIV-infected patients with increased waist circumference and impaired glucose to determine if blocking the effects of aldosterone will ameliorate cardiovascular risk parameters.
Amy Fleischman, M.D. received her MD from Johns Hopkins and completed her residency and endocrinology fellowship at the Children’s Hospital in Boston. Dr. Fleischman is currently an Assistant Professor of Pediatrics at Harvard Medical School and the Medical Director of the Optimal Weight for Life, obesity clinic at Children's Hospital Boston. and has received numerous awards including the Children’s Hospital Boston Faculty Career Development Fellowship and the Lilly Fellowship Award from the Endocrine Society. Dr. Fleischman has investigated the IKK Beta/NF kappa Beta pathway in inflammation and used salicylates to improve glycemia in high risk young adults. She has investigated the relationship of mitochondrial dysfunction to insulin resistance using MR spectroscopic and DNA techniques. She has shown for the first time using P31 spectroscopy that reduced mitochondrial function in children identifies a specific phenotype characterized by insulin resistance and dyslipidemia, independent of obesity. Her current projects focus on the investigation of mitochondrial dysfunction in pediatric obesity, in home exercise interventions to target high risk children, and telemedicine in pediatric obesity.
Janet Lo, M.D., M.Sc. is an Assistant Professor of Medicine at Harvard Medical School. Her research involves the investigation of cardiovascular disease and fat redistribution in HIV disease. She is currently performing 64 slice CT to compare plaque volume and monocyte activation in HIV vs. non HIV-infected patients and has shown an increased prevalence of subclinical atherosclerosis in HIV infected patients. She recently published an important paper in JAMA demonstrating the long-term effects of physiological Growth Hormone to reduce visceral fat in HIV-infected patients.
Hideo Makimura, M.D., Ph.D. received his MD and PhD degrees from the Mount Sinai School of Medicine in New York City where he studied the role of hypothalamic neuropeptides in the regulation of metabolic phenotype in various mice models. He subsequently completed his Internal Medicine residency at the Beth Israel Deaconess Medical Center and his Endocrinology fellowship at the Massachusetts General Hospital, both in Boston. Dr. Makimura is currently an Assistant Professor of Medicine at Harvard Medical School. He has completed several clinical studies evaluating the role of reduced growth hormone secretion in mediating cardio-metabolic complications of obesity. More recently, he has focused on determining the role of skeletal muscle mitochondria as it relates to cardio-metabolic complications of obesity and is investigating various strategies to improve mitochondrial function in obesity.
Takara Stanley, M.D. is a Pediatric Endocrinologist and Instructor in Pediatrics at MGH. She has recently shown that relative overweight may confound GH stimulation testing in the pediatric outpatient setting and demonstrated the degree to which increased BMI predicts reduced GH responsivity to standardized GH testing in this population. She is now assessing the physiological effects of GHRH1-44 and GH on endogenous GH pulsatility in healthy subjects. In a novel study, she recently demonstrated that blocking TNF-alpha in obesity reduced glucose and improved adiponectin and VCAM.
Martin Torriani, M.D. is an Assistant Professor and holds a primary appointment in the Division of Musculoskeletal Radiology. He is an expert on the quantification of intramyocellular lipid using MR spectroscopy and pioneered the technique at MGH. He has first authored a number of critical papers in the field, including a recent Editorial on the clinical significance of racial differences in intermuscular fat in the American Journal of Clinical Nutrition. He is investigating the novel use of MR to determine the effects of inhibition of lipolysis on IMCL and PET to investigate brown fat in HIV lipodystrophy.
Virginia (Jeanne) Triant, M.D., M.P.H. is an Instructor in Medicine at Harvard Medical School and a physician in the Massachusetts General Hospital (MGH) Infectious Diseases Division. She received her MD from the Yale School of Medicine and MPH from the Harvard School of Public Health. She completed her residency in internal medicine at Brigham and Women's Hospital (BWH) and fellowship in infectious diseases at the combined Partners (MGH/BWH) Program. Her research focuses on the epidemiology of increased cardiovascular disease risk and chronic disease complications among HIV-infected patients, and she has developed a longitudinal HIV cohort with which conduct clinical investigations. In important publications, she has demonstrated a 1.75-fold increase risk of acute myocardial infarction (AMI) in HIV-infected patients compared to non HIV-infected patients in a large healthcare network. She has also shown that CRP is increased and useful to predict AMI in the HIV population and that decreased CD4 cell count is associated with increased AMI risk.
Markella V. Zanni, M.D. is an Instructor of Medicine at Harvard Medical School. Her research centers on the role of inflammation in mediating cardiovascular and metabolic risk in a variety of disease states including HIV and obesity. She has studied the metabolic activity of lipoatrophic fat in patients with HIV lipodystrophy, using 18FDG-PET/CT technology. She has also published on the effects of TNF-alpha antagonism on cardiometabolic parameters in obese subjects, and on the relationship between sCD163 (a monocyte/macrophage activation marker) and insulin resistance in normal-weight and obese subjects.
Ewelinka (Nika) Grzejka, B.S received her degree in Health Management and Policy from The University of New Hampshire. She serves as an Office Manager for the Program and coordinates all grant submissions for funding consideration. She is also responsible for managing the Program's overall financial performance including budgeting and forecasting.
Linda Pronjari, B.S. received her Bachelors of Science degree in Health Management and Policy from The University of New Hampshire.She serves as a staff assistant to Dr. Grinspoon and directs the administrative aspects of the Program.
Mitochondrial Function in Pediatric Obesity
Mitochondrial function may be related to the development of insulin resistance and diabetes mellitus. In this study, we will evaluate glucose metabolism and mitochondrial function using a noninvasive, safe MRI procedure. The 2 visit study is enrolling healthy children ages 8 to 18 years old that are overweight or normal weight.
For more information contact Dr. Amy Fleischman at 617 643-4420 or 617 724-3572
Physiologic Effects of Long Term GHRH1-44 in Abdominal Obesity
Obesity is associated with reduced levels of growth hormone and increased metabolic and cardiovascular disease risk. In this study, we will administer a growth hormone releasing hormone (GHRH1-44) analog to obese subjects with reduced growth hormone to normalize growth hormone levels and to reduce visceral adiposity and improve metabolic and cardiac risk factors. This is a randomized, placebo-controlled, double-blind, interventional study lasting 12 months.
For more information contact Dr. Hideo Makimura at 617-726-1696 or 617- 726-8277.
Prevalence and Metabolic Consequences of Relative Growth Hormone Deficiency in Abdominal Obesity
Obesity is associated with reduced levels of growth hormone as well as increased metabolic and cardiovascular disease risk. In this study, we will evaluate growth hormone levels as well as metabolic and cardiovascular risk factors in lean and obese subjects to determine whether reduced levels of growth hormone are associated with increased metabolic and cardiovascular risk. The study involves three half day visits with an optional fourth visit.
For more information contact Dr. Hideo Makimura 617-724-0248 or 617- 726-8277
Assessment of Cardiovascular Risk in HIV Patients
Past research has shown that individuals with HIV may be at greater risk for heart disease than the general. In this observational study we will follow HIV-infected men and women and HIV-negative men and women every 6 months over a 2 year period. The potential benefits from this study include evaluation of overall body composition, cardiovascular health, glucose tolerance, and insulin metabolism related.
For more information contact Kathleen Fitch, NP at 617-724-8015
Strategies for the Treatment of HIV Associated Metabolic Syndrome
This research study aims to assess the effectiveness of lifestyle modification and drug treatment on HIV associated Metabolic Syndrome. Metabolic syndrome is a cluster of characteristics such as high blood pressure, high cholesterol, large waist circumference, and insulin resistance. Lifestyle modification, including monitored exercise sessions and dietary counseling, and the drug metformin are two strategies that are likely to improve the health status of individuals with HIV associated Metabolic Syndrome. In the study, patients will be randomly assigned to undergo an intensive lifestyle modification program and/or metformin therapy. The potential benefits from this study include improved overall body composition, cardiovascular health, glucose tolerance, and insulin metabolism related to HIV associated Metabolic Syndrome.
For more information contact Kathleen Fitch, NP at 617-724-8015
Short Term Effects of Growth Hormone and Growth Hormone Releasing Hormone in HIV- and Non-HIV Infected Patients
Previous studies suggest that both growth hormone (GH) and growth hormone releasing hormone (GHRH) may be useful treatments for individuals with HIV-infection who have also experienced increased abdominal fat. In this study, we look at the short-term effects GH and GHRH on the brain's own growth hormone secretion as well as glucose metabolism both in HIV-infected men and women and in non-HIV infected healthy men.
For more information, call Takara Stanley, MD, at 617-726-5312.
Subclinical Atherosclerosis in HIV-Infected Men and Women
Cardiovascular risk has been found to be increased in HIV-infected individuals. However, the factors mediating cardiovascular risk in HIV-infected individuals are unclear. In this study, we will examine the prevalence of coronary artery disease in HIV-infected individuals as well as healthy controls. Participants will be assessed by a CT scan of the heart and evaluated for metabolic and inflammatory factors associated with coronary artery disease.
For more information, please call Jeffrey Wei at 617-724-8070 or Dr. Janet Lo 617-724-3425.
Effects of Exercise in Mitochondrial Function in Pediatric Obesity
Overweight pediatric patients with reduced mitochondrial function by P31 spectroscopy will be randomized to a 3 day a week outpatient exercise program using Wii® exercise bicycles.
For more information contact Dr. Amy Fleischman at 617 643-4420 or 617 724-3572
Effects of Statins on Inflammatory Indices in HIV-Infected Patients
HIV-infected subjects with evidence of subclinical atherosclerosis on 64 slice coronary CT angiography will be randomized to atorvostatin or placebo for 12 months. The effects of atorvostatin on plaque progression and coronary inflammation using FDG PET will be determined.
For more information, please call Jeffrey Wei at (617) 724-8070 or Dr. Janet Lo 617-724-3425.
Assessment of Brown Fat in HIV Lipodystrophy
In this study, the presence of brown fat will be assessed in HIV-infected patients with dorsocervical fat accumulation (buffalo hump) using FDG PET and UCP-1 expression testing.
For more information contact Kathleen Fitch, NP at 617-724-8015
Training is a major focus of the Program in Nutritional Metabolism. Dr. Grinspoon, Program Director has been successful in training research fellows in metabolism-related clinical research for over 15 years and received a K-24 mentoring award from the NIH in this regard. In addition, he is the Principal Investigator of a Harvard Wide Training Grant in Nutritional Metabolism. Nine recent fellows have obtained mentored, K grants, six of whom Dr. Martin Torriani, Dr. Amy Fleischman, Dr. Janet Lo, Dr. Virginia Triant, Dr. Sara Looby and Dr. Takara Stanley are now faculty members, investigating effects of increased intramyocellular lipid on insulin resistance in HIV-infected patients (Dr. Martin Torriani), mitochondrial function in pediatric obesity (Dr. Amy Fleischman), subclinical atherosclerosis in HIV disease (Dr. Janet Lo), the incidence of myocardial infarction in HIV (Dr. Virginia Triant), effects of HIV on bone density in menopausal women (Dr. Sara Looby), and effects of TNF-alpha on inflammation in obesity (Dr. Takara Stanley). Dr. Lo has received a Masters Degree from Harvard Medical School in Clinical Investigation and Dr. Triant an M.P.H. from the Harvard School of Public Health. Two recent fellows received National Research Service Awards from the NIH to study the effects of TNF inhibition in the metabolic syndrome (Dr. Markella Zanni) and the effects of GH and GHRH on endogenous GH pulsatility (Dr. Takara Stanley). A prior fellow, Dr. Meininger is now currently a Director for Clinical Research in Metabolism at Merck Pharmaceuticals. Cross-training and fertilization resulting from the rich network of collaborating programs at Harvard is a strength of the Program, which facilitates interdisciplinary training in sophisticated clinical and translational nutrition research techniques through a select group of well-established Program Faculty in related fields of nutrition and metabolism research.
The Program in Nutritional Metabolism serves as the coordinating site and Dr. Grinspoon is the Principal Investigator of the Harvard Training Program in Nutritional Metabolism, an NIH-funded T32 Program. The Training Program offers three NIH-funded training slots for qualified M.D. and Ph.D.'s interested in related research fields. The Executive Steering Committee of the Grant includes Steven Grinspoon, M.D., Joseph Avruch, M.D. (MGH), Alan Walker, M.D. (MGH), Joseph Majzoub, M.D. (Children’s Hospital), Madhu Misra, M.D. (MGH), Jose Florez, M.D. (MGH), Walter Willett, Ph.D. (Harvard School of Public Health).
To Learn More about Training Opportunities, contact Dr. Steven Grinspoon, (617) 724-9109
NUTRITION OBESITY RESEARCH CENTER AT HARVARD
CALL FOR PILOT FEASIBILITY PROJECT (PFP) APPLICATIONS IN NUTRITION, OBESITY
OR RELATED RESEARCH FIELDS
(NEW AND COMPETING RENEWALS)
DEADLINE: April 22, 2015
The Nutrition Obesity Research Center at Harvard (NORC-H) (previously known as Harvard Clinical Nutrition Research Center) will be accepting applications for new pilot/ feasibility projects as well as for competing renewals of currently funded one-year projects for the 20th year (08/01/2015-07/31/2016) of the NIH-supported NORC. Projects will be funded up to $20,000 in the first year with possibility for renewal for a second year.
The specific purpose is to find:
1. Young investigators (senior fellows* or junior faculty) established by research programs relevant to clinical research who are without NIH R01 and R21 grant support (K awardees are encouraged to apply).
2. Established scientists not currently focused on nutrition per se who wish to initiate studies of direct or indirect importance to nutrition, metabolism or obesity.
3. Established nutrition researchers with novel new projects distinctly removed from their currently funded research projects.
Applications should be in the format of an R01, including all the NIH forms and budget pages, with the text portion of the grant limited to 3-5 pages single-spaced (NIH PHS 398). For anyone planning to submit a continuation, please be certain to detail the progress you have made in the first year, as well as your plans for the proposed second year.
In addition, please suggest 3 or 4 individuals who might be able to review your application knowledgeably. These individuals can be from within or outside the Nutrition Obesity Research Center, but should not be current collaborators. Please include their full names, mailing addresses, telephone and fax numbers and e-mail address.
All applications should be received in the NORC office by April 22, 2015. Please submit electronically to Ewelinka ‘Nika’ Grzejka at firstname.lastname@example.org . FOR A COMPLETE APPLICATION GO TO THE NORC WEBSITE
For any science related questions please contact Dr. Steven Grinspoon, Co-Director of the NORC and Director of the Pilot Feasibility Program at 617-724-9109
* Fellows must be in the final year of training and must have a documented commitment to a faculty appointment by a sponsoring division or department.
PublicationsView recent publications from the Program in Nutritional Metabolism. Some full text articles may require a subscription.
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Dr. Steven Grinspoon
Director, MGH Program in Nutritional Metabolism
Ewelinka Grzejka, B.S