Genetic and Environmental Determinants of Pubertal Development
- Natalie D. Shaw, M.D., MMSc.
- Tel 984-287-3716
- P.O. Box 12233Mail Drop A2-03Durham, N.C. 27709
Natalie Shaw, M.D., MMSc., heads the Pediatric Neuroendocrinology Group and holds a secondary appointment in NIEHS Reproductive and Developmental Biology Laboratory.
The Pediatric Neuroendocrinology Group has three major research foci:
- To investigate the contributions of body weight, abnormal sleep patterns, and other environmental factors to irregular menstrual cycles in adolescent girls during the first few years after menarche (a girl's first period).
While irregular menstrual cycles are a common part of female development, a subset of teens never make the critical transition to normal menstrual cycles. By investigating the physiologic and pathophysiologic underpinnings of irregular menstrual cycles in adolescent girls in the 1-2 years after their first menses, the Pediatric Neuroendocrinology Group intends to identify those girls who are at high-risk for reproductive dysfunction as adults. Girls with pathologic menstrual cycle patterns would then be encouraged to seek early treatment to prevent future hormonal and metabolic complications.
- To determine the influence of obesity on pubertal timing in girls.
Over the past decade, there has been an alarming trend toward earlier breast development in girls. The contemporaneous obesity epidemic has led to speculation that obesity may be driving early puberty. However, questions remain about the validity of reports of early puberty among obese girls due to the difficulty in distinguishing fatty tissue from breast tissue by palpation in this population. The physiological basis for early puberty among obese girls is also unknown.
The group initiated the NIEHS Body Weight & Puberty Study in 2016 to investigate pubertal development in obese compared with normal weight girls using more robust methods such as breast ultrasonography. Study procedures also include blood draws, DXA (for body composition), hand x-ray (for bone age), transabdominal (pelvic) ultrasounds, and anthropometrics (height, weight, BMI, waist-hip ratio). Nearly 80 girls have enrolled in this study which remains open to enrollment and is being conducted at the NIEHS Clinical Research Unit.
- To determine the genetic architecture of Bosma Arhinia Microphthalmia Syndrome, a rare syndromic form of hypogonadism.
Patients with Bosma syndrome are born without an external nose (arhinia) and with small or absent eyes (microphthalmia or anophthalmia). They also don’t undergo puberty and are infertile (hypogonadotropic hypogonadism). This condition is extremely rare, with fewer than 100 cases reported worldwide in the past century. Working with scientists at Harvard University, Duke University, and the University of Edinburgh, the group determined that mutations in the gene SMCHD1 are the primary genetic cause of Bosma syndrome. The group is now working to identify additional genetic and environmental factors that contribute to this syndrome.
Shaw received a B.S. from Cornell University, an M.D. from the State University of New York (SUNY) at Buffalo, and a Masters in Medical Sciences (MMSc) from Harvard Medical School. She completed her pediatrics residency at Children's Hospital of Pittsburgh, a pediatric endocrinology fellowship at Boston Children's Hospital, and a clinical research fellowship in the Reproductive Endocrine Unit at Massachusetts General Hospital.
In 2015, Shaw was one of five junior investigators selected as a Lasker Clinical Research Scholar by the National Institutes of Health. The Lasker program is a joint partnership between the NIH and the Lasker Foundation designed to support a small number of exceptional clinical researchers in the early stages of their careers. Its goal is to promote the development of physician-scientists as they transition to fully independent positions. When Shaw joined NIEHS Sep. 2015, she became the first Lasker Scholar in the history of the institute.
Relevance to NIEHS Mission
This work will identify environmental and genetic factors that produce normal or aberrant pubertal development. The underlying biological pathways will then be dissected using clinical investigative tools in pediatric subjects. The results of these studies will inform strategies to prevent and/or treat common pubertal disorders such as precocious puberty, delayed puberty, and irregular menses.