Fellows in the Pediatric Endocrinology Fellowship Program at MassGeneral Hospital for Children have the opportunity to work with faculty whose interests include the neuroendocrine maturation of human puberty and modulating transcription factor function in the pancreatic beta cell.
- Pediatric Endocrinology Fellowship
Faculty Research Interests
Paul A. Boepple, MD
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
My laboratory was the first to describe the use of alternative substrates to glucose by the neonatal primate brain, and to document gluconeogenesis in fetal life. We now work on modulating transcription factor function in the pancreatic beta cell in order to reconstruct the beta cell in other cell types. We have developed a “superpromoter” transcription factor which enhances action in cell types cognate with beta cells. 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 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. We also will be participating in studies of long-acting growth hormone products in children with growth hormone deficiency.
Michelle Katz, MD, MPH
My research interests surround improving health care practice and delivery to diminish the impact of type 1 diabetes on families and to decrease the rate of diabetes complications. In a national data set, I have studied the association of health care delivery consistent with the medical home model with a family's ability to continue working, decrease out-of-pocket medical expenses, and diminish financial and time-related demands. To follow-up this research, I am validating an original survey on the family impacts of diabetes. I worked on a studies to determine if frequent outreach to patients in addition to psycho-education improves diabetes related quality of life and glycemic control (A1c), the optimal insulin regimen to decrease the frequency of severe hypoglycemia in contemporary adolescents with type 1 diabetes, and the associations between high fat and low fiber diets and glycemic control in type 1 diabetes. I am currently evaluating the contributions of weight status and glycemic control to cholesterol in youth and young adults with type 1 diabetes. In addition, I am a co-investigator on a longitudinal study looking at improving adherence with continuous glucose monitoring in youth with type 1 diabetes and the site Primary Investigator on a study to improve glycemic control in overweight youth with type 1 diabetes with metformin plus insulin.
Rose Marino, MD
Dr. Marino has worked with Dr. Baron’s group at the NIH in characterizing the physiology and endocrine regulation of the growth plate. She has demonstrated that catch-up growth after hypothyroidism is consequent to delayed growth plate senescence. Her current research interests lie in examining the endocrine consequences of proton beam radiation therapy administered for treatment of pediatric brain tumors. She is also looking at the natural history of the endocrine manifestations in adrenal leukodystrophy.
Madhusmita Misra, MD, MPH
My research to date has focused on clarifying neuroendocrine, body composition and bone alterations in conditions that span the nutritional spectrum from nutritional deprivation (anorexia nervosa) to excess (obesity). My research has contributed significantly to the understanding of low bone mass accrual in teenagers with anorexia nervosa, and in addition to low bone density, I have reported impaired bone microarchitecture and decreased bone strength in this population, and an increased risk for fractures compared to healthy girls. I have worked on therapeutic strategies to optimize bone accrual in adolescents with anorexia nervosa, and have demonstrated the efficacy of physiologic estrogen replacement in increasing bone accrual, although complete catch-up does not occur, likely because other hormonal alterations persist. I have demonstrated that rhIGF-1administration over the short-term in replacement doses is effective in increasing bone formation rates in adolescents with anorexia nervosa, and our group is currently examining the impact of IGF-1 with physiologic estrogen replacement on bone in this condition. Finally, through a recently funded grant, we will explore 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.
More recently, I have expanded my work to teenage athletes in order to understand the impact of subtle energy deficit states on the hypothalamo-pituitary-gonadal (H-P-G) axis and bone accrual, and my 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. My current grant aims at developing 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, I have examined neuroendocrine predictors of site specific fat depots in obese adolescents, an important determinant of the metabolic syndrome, and the implication of specific macronutrients on hunger and food intake. I am currently principal investigator and co-investigator of various NIH studies.
David Rhoads, PhD
We have two major research interests. First, in an effort to engineer cells capable of regulated insulin secretion, we are examining strategies to exploit pancreatic β-cell transcription factors to reconstruct this function in other cell types. To this end, we are engineering key transcription factor genes able to convert (reprogram) cells toward β-cell functionality. In an important advance, we developed a technique to boost native gene promoter activities several hundred-fold. Driving engineered genes with “augmented” native promoters is anticipated to preserve innate control of expression and avoid the untoward side-effects observed with the strong, constitutive viral promoters in current gene therapy vectors. Ultimately, incorporating intrinsic control mechanisms could greatly expand the therapeutic potential of gene transfer protocols. Second, in collaboration with a bariatric surgeon at Brigham and Women’s Hospital, we are characterizing mechanisms by which Roux-en-Y gastric bypass (RYGB) improves metabolic function within days of surgery, independent of weight loss. The increasing incidence of obesity and associated type 2 diabetes (DM2) is an urgent health crisis. Currently, bariatric surgery is the only proven weight-loss therapy, with RYGB providing the best outcomes and, remarkably, rapidly resolving or improving DM2 when present in obese bariatric patients. To understand this metabolic benefit, we are examining intestinal glucose sensing and absorption, known to be dysregulated in obesity and DM2, as central to the effect of RYGB. We have shown that RYGB restores regulation in a rodent surgical model. Current efforts are directed to determine how this occurs and to reproduce beneficial changes pharmacologically. These studies are hoped to reveal less invasive alternatives suitable for a wider range of patients and/or to enhance surgical outcomes.
Eray Savgan-Gurol, MD
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.
Nicole Sherry, MD
Dr. Sherry's research interests include type 1 diabetes, especially research related to immune therapy to alter the autoimmune response in type 1 diabetes. She is the principal investigator in several Phase I/II/III trials involving novel immune modulatary therapies in recent onset type 1 diabetes. She is also a co-investigator in the development of a drug delivery device currently in trials in adolescents and adults with type 1 diabetes at MGH. This is a device that responds to glucose concentrations to automatically avoid both high and low blood glucose, a so-called artificial endocrine pancreas. It uses frequent measurements of blood glucose concentration along with subcutaneous delivery of both rapid-acting insulin and glucagon (to raise blood glucose, if necessary) as directed by a computer algorithm. She is involved in the Type 1 Diabetes Exchange, an information exchange designed to drive a better understanding of the disease, improve care and accelerate new therapies for type 1 diabetes through the promotion of collaborative research and data sharing, as well as the TODAY study (Treatment Options for type 2 Diabetes in Adolescents and Youth). She is interested in research involving practice improvements to improve quality and safety of diabetes care in the MGHfC inpatient and outpatient settings.
Takara Stanley, MD
My research interest is the clinical investigation of metabolic and endocrine perturbations associated with abnormal body composition, particularly in HIV-infection and in pediatric obesity. I am particularly interested in the interactions between growth hormone dynamics and body composition, ectopic fat accumulation, lipid metabolism, glucose homeostasis. I have worked on projects investigating growth hormone dynamics in patients with HIV lipodystrophy, with special attention to the effects of exogenous Growth Hormone and Growth Hormone Releasing Hormone (GHRH) on endogenous growth hormone secretion, insulin sensitivity, and ectopic fat accumulation in liver and muscle. I am also interested in the process of evaluating growth hormone deficiency in children, the effect of body composition on endogenous GH secretion, and the use of growth hormone in pediatric populations, including children with Prader Willi, small for gestational age, and Turner syndrome. My recent work focuses on metabolic and endocrine associations with nonalcoholic fatty liver disease and the effects of augmenting growth hormone to ameliorate hepatic steatosis and steatohepatitis.
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