Faculty Research Interests
Paul A. Boepple, MD |Publications
My research contributions have focused on the neuroendocrine maturation of human puberty and the modulation of childhood and adolescent growth through the interactions between the reproductive and growth hormone axes. Investigations have predominantly employed clinical models of human puberty, including children with sexual precocity, adolescents with delayed puberty, and adults with deficiencies of gonadotropin-releasing hormone. In addition to providing physiological insights, the data we compiled in our studies of children with precocious puberty (CPP) were the basis for the first FDA approval of the use of GnRH agonists for this indication. Since that approval in 1991, GnRH agonist therapy of children with CPP has become the standard of care around the world. Subsequently, investigations undertaken with colleagues in the MGH Reproductive Endocrine Unit helped elucidate the complex interaction of GnRH, sex steroids, and inhibin in the differential regulation of LH and FSH in the human male through the study of a variety of clinical research models (children with CPP before, during, after treatment with GnRH agonists; men with GnRH deficiency before and after restoration of a normal, adult testosterone levels by administration of pulsatile GnRH; adult male volunteers before and after short-term, reversible “biochemical castration” achieved by high-dose ketoconazole). I continue to contribute to clinical research studies in the MGH Reproductive Endocrine Unit that characterize the phenotype/genotype correlations in adult subjects with hypogonadotropic hypogonadism and then seek insights into the genetic basis for variations in pubertal timing and reproductive disorders. Most recently, sequencing of a set of genes known to underlie GnRH deficiency was undertaken in patients with delayed puberty and hypothalamic amenorrhea.
Lynne L. Levitsky, MD |Publications
My major clinical research work focuses on the continuation of the TODAY study, an NIH-funded trial of treatments for type 2 diabetes in children and Adolescents. We have demonstrated that the “fat paradox”, the protective effect of obesity on complications of diabetes, extends to retinopathy in the young. The mechanism of this effect, looking at important metabolic factors, is presently being examined. The patients in this trial are being followed into adulthood so that the natural history of type 2 diabetes in young people can be elucidated. I also am involved with a study of the effects of videogame usage on exercise and fitness in children.
Michelle Katz, MD, MPH |Publications
Dr. Michelle Katz conducts clinical and health services research as an Assistant Investigator within the Section on Clinical, Behavioral and Health Outcomes Research at the Joslin Diabetes Center in Boston, MA. Her research focuses on improving the health and well-being of youth with type 1 diabetes and their families. She is currently investigating improvements in management of cardiovascular risk factors in youth with type 1 diabetes.
Deborah Mitchell, MD |Publications
Dr. Mitchell's research is concerned with factors which promote optimal bone growth and mineralization during childhood and adolescence, with a goal of preventing osteoporosis and fractures in adults. She is currently investigating bone accrual and microarchitecture in children with type 1 diabetes, a condition known to increase the risk of bone fragility. Her goal is to better understand why patients with diabetes are at increased risk of fracture in order to be able to design and test therapies to strengthen bones in this population. In addition, Dr. Mitchell is interested in rare disorders of calcium and phosphate metabolism including hypoparathyroidism, pseudohypoparathyroidism, and X-linked hypophosphatemic rickets. In particular, her research has demonstrated extremely high rates of kidney disease among patients treated for hypoparathyroidism. Ongoing studies are investigating determinants of renal disease in this population as well as novel, targeted therapies.
Madhusmita Misra, MD, MPH |Publications
Dr. Misra’s research to date has focused on clarifying neuroendocrine and bone alterations in conditions that span the nutritional spectrum from nutritional deprivation (anorexia nervosa) to excess (obesity). Data from the Pediatric Endocrine-Neuroendocrine-Sports Endocrine Laboratory (Misra Lab) has contributed greatly to the understanding of low bone mass accrual in teenagers with anorexia nervosa, and in addition to low bone density, the group has reported impaired bone microarchitecture and decreased bone strength in this population, and an increased risk for fracture compared to healthy girls. Dr. Misra has worked on therapeutic strategies to optimize bone mass in adolescents with anorexia nervosa, and demonstrated the efficacy of physiologic estrogen replacement in increasing bone accrual. She has also demonstrated the efficacy of IGF-1 replacement over the short-term in increasing bone formation. Dr. Misra is currently studying whether rhIGF-1 given with physiologic estrogen replacement further increases bone accrual rates to allow for ‘catch-up’ to occur (not seen with estrogen replacement alone). Finally, through another grant, the group is exploring whether alterations in food motivation pathways in specific brain regions underlie restricting, bingeing, and purging in girls with low-weight eating disorders, and whether these alterations are associated with long-term outcomes. Dr. Misra also studies teenage athletes to understand the impact of subtle energy deficit states on the hypothalamic-pituitary-gonadal (H-P-G) axis and bone accrual, and her studies indicate that adipokines and certain appetite regulating peptides affected by energy status are possible mediators of the association between low fat mass and suppression of the H-P-G axis in amenorrheic athletes, and may contribute to low bone density. Another grant has examined therapeutic strategies to optimize bone health in female amenorrheic athletes in the critical teenage years, when disruption of bone accrual may lead to permanent deficits in peak bone mass, an important determinant of long-term bone health. At the other end of the nutritional spectrum, the Misra Lab has examined neuroendocrine predictors of site specific fat depots in adolescents with obesity, an important determinant of the metabolic syndrome, and the implication of specific macronutrients on hunger and food intake. The group is currently examining the impact of bariatric surgery on bone outcomes in adolescents and young adults. Other areas of research include major depressive disorders and autism spectrum disorders. Dr. Misra’s work with investigators at the Lurie Center for Autism has shown lower bone density in peripubertal boys with autism compared with typically developing controls, and a higher risk of certain types of fracture in children and adults with autism spectrum disorders compared with controls. She is currently principal investigator and co-investigator of several NIH studies.
Website:MGH Adolescent Neuroendocrine Unit
Eray Savgan-Gurol, MD |Publications
Dr. Savgan-Gurol has worked on maternal vitamin D gene polymorphisms that may predispose to premature birth, and on techniques used to assess regional body composition to best determine clinical and DXA surrogates for visceral and subcutaneous fat and intramyocellular lipid, as analyzed by MRI and MRS techniques. She is currently working on a project examining endocrine consequences of proton beam radiation administered for treatment of pediatric brain tumors.
Vibha Singhal, MD |Publications
Dr. Singhal’s research interests include investigations of causes and treatments of obesity and its complications. Her goal is to eventually find a personalized treatment for obesity in children which is a multifactorial and complex disorder. She envisions streamlining the care of patients with obesity so that they can have a medical home to solve their weight struggles at Mass General. She is currently NIH funded to explore the changes in insulin secretion after weight loss surgery in adolescents and young adults. Dr. Singhal also has interest in evaluation of bone outcomes in extremes of spectrums – anorexia nervosa to severe obesity. She has evaluated the role of different fat depots – visceral, subcutaneous, marrow and brown fat and their contribution to bone and metabolic consequences in various disease states like athletic triad and anorexia and is actively researching the impact of obesity on developing bone.
Manasi Sinha, MD |Publications
Dr. Sinha’s research interests include insulin delivery methods in patients with Type 1 diabetes. She is currently working with Dr. Steven Russell on studies in children using the closed loop system of insulin delivery (the bionic pancreas).
Takara Stanley, MD |Publications
My research interest is the clinical investigation of metabolic and endocrine perturbations associated with abnormal body composition, particularly in HIV-infection and obesity. I have worked on projects investigating growth hormone dynamics in patients with HIV lipodystrophy, with special attention to the effects of exogenous Growth Hormone (GH) and Growth Hormone Releasing Hormone (GHRH) on endogenous growth hormone secretion, insulin sensitivity, and ectopic fat accumulation in liver and muscle. I am currently involved in projects investigating the effects of GH on liver fat content in young adults, and the effects of GHRH on nonalcoholic fatty liver disease and steatohepatitis in adults. Additionally, I work on characterizing endocrine aspects of Williams Syndrome, with recent work showing that individuals with Williams may have reduced bone density and reduced lean mass.