Wednesday, September 9, 2020

CCMB Seminar: "Birth defects affecting neuroendocrine function: three bioinformatic vignettes"

4:00 PM to 5:00 PM

This seminar will be web stream only

CCMB Seminar Series – sponsored by DCMB
by Dr. Sally Camper


Birth defects that interfere with craniofacial development can result in cognitive, neurosensory, and neuroendocrine defects that create life-long burdens for care.  The forebrain, midbrain, hindbrain, five facial prominences, and pituitary gland develop between the first and second month of gestation in humans. Genetic defects that disrupt these processes cause a spectrum of disorders that range from holoprosencephaly (HPE) and septo-optic dysplasia (SOD) to pituitary hormone deficiencies.   We screened a large cohort of Argentinean patients with congenital hypopituitarism and related disorders for mutations in known genes and identified novel pathogenic variants and examples of digenic disease.  However, the majority of patients did not receive a molecular diagnosis, indicating the high degree of genetic complexity underlying these disorders and the need for additional gene discovery.  The majority of known hypopituitarism genes were discovered through basic research in pituitary cell lines and mutant mice.  To identify novel regulatory genes for pituitary organogenesis we analyzed differential binding of a key pituitary-specific transcription factor, POU1F1, in cell lines that represent pituitary progenitors and differentiated cells.  We discovered that POU1F1 binding is associated with bZIP transcription factors in progenitors and with bHLH factors in differentiated cells.  We also applied single cell RNA sequencing technology to analyze gene expression during pituitary organogenesis and discovered novel transcription factors that are candidates for driving cell specification as well as unique, rare cell types that are likely differentiation intermediates.  Bioinformatic analyses have played key roles in advancing our knowledge of neuroendocrine birth defects and normal pituitary organogenesis.

Sally Camper, Ph.D.

Margery Shaw Distinguished University Professor of Human Genetics
Professor of Internal Medicine