The overarching goal of our research is to understand the causes of birth defects, including the genes involved and the mechanisms of pathological manifestations, to develop molecular diagnostics, and explore treatment efficacy. Our research is focused on understanding the genetic control of hypothalamus and pituitary gland development and function and how mutations cause growth insufficiency, hypothyroidism, delayed puberty, infertility, metabolic abnormalities, and abnormal stress response. The pituitary gland and hypothalamus are located in the midline of the developing fetus, and birth defects affecting these organs can present with syndromic features affecting the face, brain, vision, hearing, and sense smell, as well as structural defects in other organ systems. Congenital hypopituitarism is a common, genetically heterogeneous disorder, that is part of a spectrum spanning from holoprosencephaly and septo-optic dysplasia to isolated growth hormone deficiency and hypogonadotropic hypogonadism.
Over 30 genes have been implicated in congenital hypopituitarism, but 70-80% of patients have no molecular diagnosis. We seek to identify additional genes that contribute to this important class of birth defects, as part of an international collaboration with pediatric endocrinologists and geneticists. We use cell cultures and animal models to test the function of variants of unknown significance that we find in patients and to understand the pathophysiology of disease associated with lesions in novel genes.