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.
Ishita Jindal, MD
Dr. Jindal’s research interests include clinical investigations of the association of sleep and obesity in children. Her research has demonstrated that sleep parameters such as poor sleep quantity and quality are associated with decreased physical activity and energy expenditure in children. In addition, she is also interested in investigating cardiometabolic outcomes in children with obesity and youth onset diabetes. She is currently examining knowledge, attitudes, practices and beliefs of physicians for management of obesity with weight loss surgery in children and adolescents.
Jacqueline Maya, MD
Dr. Maya’s interests lie in understanding modifiable risk factors that contribute to the development of childhood obesity to work towards interventions that decrease the risk of developing diabetes and other long term cardiometabolic complications over the life course. Her research focuses on identifying children that are most at risk as early as possible to intervene using targeted preventative approaches, with a focus on obesity risk factors during the prenatal period.
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 weight spectrum from anorexia nervosa to the female athlete with amenorrhea to obesity. She has also worked on bone outcomes in children with autism spectrum disorder and type 1 diabetes. Studies from the Pediatric Endocrine-Neuroendocrine-Sports Endocrine Laboratory (Misra Lab) have contributed greatly to the understanding of low bone density and impaired bone accrual in teenagers with anorexia nervosa and athletes with amenorrhea, and the pathophysiology underlying these changes. Dr. Misra has worked on therapeutic strategies to optimize bone mass in adolescents and young adult women with these conditions, and demonstrated the efficacy of physiologic estradiol replacement administered as the transdermal patch (with cyclic progesterone) (but not the oral contraceptive pill) in increasing bone accrual. She has also demonstrated the efficacy of IGF-1 replacement over the short-term in increasing bone formation in young women with anorexia nervosa; however, addition of recombinant IGF-1 to young women receiving physiologic estradiol replacement with cyclic progesterone does not further improve bone outcomes. Through another grant, the group is exploring whether alterations in food motivation pathways in specific brain regions and alterations in appetite regulating peptides underlie restricting, bingeing, and purging behaviors in girls with low-weight eating disorders, and whether these alterations are associated with long-term outcomes. Dr. Misra (with Dr. Eddy) is also studying the impact of estrogen replacement on cognitive flexibility and reward responsiveness in young hypoestrogenic women with restrictive eating patterns.
At the other end of the weight spectrum, the Misra Lab has examined neuroendocrine determinants of site specific fat depots in adolescents with obesity, an important predictor of the metabolic syndrome, and the implication of specific macronutrients on hunger and food intake. The group has reported on the deleterious effect of sleeve gastrectomy on bone outcomes in adolescents and young adults with obesity, and is also examining the impact of gastric bypass on these outcomes. With her collaborators (Drs. Bredella and Lawson), Dr. Misra is examining the efficacy of intranasal oxytocin as a weight loss therapy in adolescents with obesity.
Dr. Misra’s work with investigators at the Lurie Center for Autism has demonstrated lower bone density in peripubertal and pubertal boys with autism spectrum disorder (ASD) compared with typically developing controls, and a higher risk of certain kinds of fracture in children and adults with ASD. She is collaborating with Drs. Neumeyer and Lawson at the Lurie Center and the Neuroendocrine Unit of MGH on a study examining the osteoanabolic role of intranasal oxytocin in children with ASD. She is also working with Drs. Mitchell and Bouxsein on a study examining bone accrual in children and young adults with type 1 diabetes.
Dr. Misra is currently the principal investigator or co-investigator of several NIH and DoD 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 optimize the care of children and adolescents with this chronic multifactorial and complex disorder. She leads the pediatric obesity program at the MGH Weight center and the obesity pharmacotherapy program in the division of pediatric endocrinology. Her efforts involve streamlining the care of patients by optimizing the referral of these patients in a timely manner, provide education to trainees and colleagues for stage appropriate management of pediatric obesity and 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 was funded by NIH to explore the changes in insulin secretion after weight loss surgery in adolescents and young adults and is currently collaborating on other projects like evaluating the role of oxytocin hormone in adolescents with obesity.
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.
Swathi Sethuram, MD
Dr. Sethuram is dedicated to clinical research. Her work has focused on several topics, including a clinical trial of growth hormone and its effects on repetitive behavior outcomes in children with Phelan Mcdermid Syndrome, a rare form of autism. She has also studied the effects of endocrine disruptors, phthalates, on play behavior in children, as well as the association of prenatal maternal sex hormones and play behavior in children at four years of age.
A.Kemal Topaloglu, MD
The activities of the hypothalamo-pituitary–gonadal (HPG) axis from late embryo to young adulthood provide essential inputs to human development. Dr. Kemal Topaloglu’s goal has been to gain full insight into the central regulation of the HPG axis throughout human life stages and particularly to determine what drives pubertal onset. Over the past 15 years, with the collaboration of his dear colleagues, Dr. Topaloglu has identified and seminally reported several genes associated with pubertal failure. The most notable of these are TAC3 (encoding neurokinin B), TACR3 (encoding the neurokinin B receptor), and KISS1 (encoding kisspeptin), which were instrumental in defining our current understanding of the GnRH pulse generator as the KNDy (Kisspeptin/NKB/Dynorphin) neurons in the hypothalamic arcuate nucleus. The neuropeptides, kisspeptin, and neurokinin B (encoded by TAC3 and KISS1, respectively), along with dynorphin, constitute the KNDy cells, in which each peptide had a distinct role: NKB as the start signal, kisspeptin as the output driving GnRH and dynorphin as the stop signal terminating each pulse. The reactivation of the KNDy cells at the beginning of the second decade of human life underlies the start of puberty, a major life event denoting the end of the childhood (juvenile) life stage and the beginning of another, adolescence (and subsequently young adulthood). This new life stage is characterized by developing secondary sex characteristics, psychosocial identity, and maturing reproductive capacity. Although we now roughly know the identity and inner mechanisms of the GnRH pulse generator, the stimulus that reactivates it after a prolonged quiescence during childhood to start puberty remains an enigma. Identification of such stimulus represents his current research challenge. Insufficiency of the HPG often results in delayed/absent puberty, which is a major cause of distress among affected adolescents. As a clinician, he is particularly interested in caring for children and adolescents with puberty problems.
Janaki Vakharia, MD
Dr. Vakharia’s interests are focused on improving health care delivery for young adults with chronic endocrine conditions as they transition to the adult health care setting and understanding the gaps in endocrine providers’ knowledge and resources for caring for complex young adult patients. She has designed a novel care model for young adults with diabetes that focuses on patients’ diabetes care, mental health, and overall well-being as they transition to the adult care setting. Dr. Vakharia has conducted a mixed methods pilot feasibility study on this model, and plans to continue with quality improvement, observational, and qualitative studies to better understand how to support and enhance comprehensive care for young adults with diabetes and other chronic endocrine conditions.
Rachel Whooten, MD
I am a board-certified pediatric endocrinologist with a strong interest in how health behavior like physical activity, nutrition, and sleep can be targeted to prevent endocrine complications of childhood obesity. I completed my clinical and research fellowship within the Divisions of Pediatric Endocrinology and General Academic Pediatrics at Massachusetts General Hospital, with concurrent participation in the Harvard Pediatric Health Services Research and Institute for Healthcare Improvement Fellowships as well as completion of an MPH at the Harvard School of Public Health. I am currently a junior faculty member within the Department of Pediatrics at MGH, continuing my work in both General Academic Pediatrics and Endocrinology. My prior research has focused on strategies for the implementation of physical activity promoting policies, primarily within school-based settings.
To date, I have focused on community-based physical activity policies and interventions in childcare and school settings, as well as developing early life obesity prevention initiatives. This work has provided experience in community-based physical activity programs, qualitative analyses, and the importance of engaging with community partners to develop sustainable interventions. My current work examines the development of a common endocrine condition (polycystic ovary syndrome, or PCOS) with significant morbidity among young females and examines how physical activity behaviors may impact PCOS development.