PGNB Research Programs

Program Officials: Andrew Bremer, Karen Winer, Dan Raiten

Branch efforts in this area include basic research on growth-promoting peptides, hypothalamic-releasing factors and their influence on growth, pubertal maturation, obesity, and other aspects of physiologic development; studies to understand disorders of linear growth, bone accrual, and pubertal maturation, as well as genetic determinants of skeletal deformities.

Program Officials: Andrew Bremer, Karen Winer

Studies in this research area focus on the underlying molecular physiology of congenital and acquired pituitary, thyroid, adrenal, and gonadal disorders, as well as diabetes, obesity, and the metabolic syndrome in children, in addition to the development of new therapies for these disorders.

Program Officials: Andrew Bremer, Dan Raiten

The branch studies the complex nutritional relationships between the mother and her fetus, the placental transfer of nutrients, and the role of nutrition in infant development. Research interests focus on the nutrient requirements of normal, premature, and growth-restricted infants, and on the contributions of human milk and its components to optimal infant nutrition. Studies are encouraged to assess how maternal factors affect milk composition and lactation performance.

The branch also supports studies on the effects of nutrition on growth, the onset of puberty, and the etiology, consequences, and prevention of obesity and hyperlipidemia in childhood and adolescence. Special emphasis is placed on studying molecular and biochemical aspects of nutrition, particularly in relationship to the growth of cells, tissues, organ systems, and individuals.

Additional focus includes cultural and behavioral determinants of food selection and eating behavior, particularly as they impact health promotion, disease prevention, and the etiology of eating disorders. Studies also include behavioral and neuroendocrine factors in taste, olfaction, satiety, and the control of food intake and on the behavioral and cognitive consequences of nutritional deficiencies and imbalances.

The program further emphasizes the development of new non-invasive methods for assessing nutritional status, particularly during infancy, adolescence, pregnancy, and lactation.

Program Officials: Andrew Bremer, Dan Raiten

The burdens of obesity, cardiovascular disease, diabetes, and osteoporosis continue to increase in this country and abroad. These chronic conditions are the products of gene-environmental interactions, which have their roots in utero or infancy/childhood and are difficult or impossible to reverse in adulthood. Analyses of high-throughput “-omic” data enable investigators to identify the origins of these diseases, to develop biomarkers that predict disease susceptibility, and to identify targets for interventions. PGNB encourages research that focuses on detecting the earliest aberrations in molecular and biochemical pathways that lead to disease later in life.

The branch’s broad portfolio on issues related to preventing chronic diseases emphasizes a continued need for research on childhood biomarkers for disease later in life, as well as steps which can be taken during childhood to mitigate or prevent conditions, such as atherosclerosis, metabolic syndrome, diabetes, obesity, and osteoporosis. Decision science may be useful in translating evidence-based information about childhood risk factors for these diseases into clinical practice and public health interventions.

Epigenetics is also an area of research that will help advance the branch’s interest in the molecular biology of growth and development. Epigenetic changes serve as markers of longitudinal changes during growth and development and of exposure to nutrients, stress, and xenobiotics in the environment. Gaining a better understanding of epigenetic processes could also inform an understanding of the developmental origins of health and disease. The relationship between epigenetics and the origins of health and disease is so complex that it becomes a problem of systems biology.

Program Officials: Andrew Bremer, Layla Esposito

Research priorities in this area are obesity, hyperlipidemia, and insulin resistance in childhood and adolescence. Special emphasis is placed on developing methods for detecting individuals with diabetes in childhood and for developing successful techniques of immunomodulation to prevent or mitigate the body's immune attack on the pancreatic beta cell. Similarly, studies of obesity and hyperlipidemia focus on the etiology, consequences, and prevention of childhood obesity and hyperlipidemia. Studies of calcium intake during adolescence and the prevention of osteoporosis later in life are also encouraged.

• Obesity: The branch has provided long-term support to scientists who are working to elucidate the genetic, environmental, and behavioral origins of obesity, including recent initiatives on prevention and treatment of childhood obesity. PGNB also leads an NICHD working group on obesity, including the origins and consequences of maternal obesity during pregnancy.
• Diabetes: Branch initiatives have successfully investigated continuous glucose monitoring devices and novel therapies mitigating hypoglycemia in children with type 1 diabetes mellitus (T1DM).
• Osteoporosis: Osteoporosis is a major public health problem in the United States. The origins of osteoporosis begin in childhood as bone mass accrued during childhood and adolescence determine peak bone mass in young adulthood. PGNB initiated the Bone Mineral Density (BMD) in Childhood Study (BMDCS), a longitudinal study of bone accretion to further understand this topic. Normal reference bone mass measurements play a crucial role in the diagnosis of osteoporosis in adults and deficient bone accrual in children. The study aimed to establish normal values of bone mineral content and BMD in 2,000 healthy American children, between ages 5 and 19 years, by dual X-ray absorptiometry (DXA).

As the logical extension of this work, there is a need to develop preventive strategies and therapeutic agents for pediatric bone disorders. The long-term goal is to determine ways to maximize peak bone mass and thereby reduce the burden of osteoporosis later in life.

The branch encourages studies of interventions to ameliorate bone density decrements among children with severe chronic illness, such as childhood cancer survivors or children with HIV/AIDS. Studies of genetic determinants of bone mass accrual and peak bone mass are also encouraged. Topics of programmatic interest further include the study of fat-muscle-bone interactions during childhood and adolescence and the novel regulators of bone formation.