Research

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. There are currently three main areas of research in the lab: development and function of the pituitary gland, auditory and vestibular systems, and skeletal elements.

Pituitary hormone deficiency diseases and adenomas are both common in humans. Many combined hormone deficiencies are caused by transcription factor defects. Lesions in the homeodomain transcription factor gene PROP1 are most prevalent known cause of multiple pituitary hormone deficiencies. The homeodomain transcription factor PITX2 is mutated in patients with Rieger syndrome, which can include growth deficiency. It is a member of a multigene family that exhibits overlapping functions and dosage sensitive effects. We study Prop1, Pitx2, and other pituitary transcription factor genes using genetically engineered mice, stem cells, and zebrafish.

Hearing deficits are common in humans and about half of the cases are estimated to be genetic. Environmental influences such as ototoxic drugs and low iodine diet can contribute to hearing impairment. We are studying the mechanism of action of an unconventional motor myosin MYO15 that causes hearing and balance disorder in humans and mice. In addition, we are studying the genetic factors that influence the sensitivity of cochlear development and function to thyroid hormone insufficiency. This iodinated hormone is critical for neurological and sensory cell development in some genomic contexts, while selected genetic backgrounds have protective gene(s) that we seek to identify.

Skeletal dysplasias are genetically heterogeneous and significant contributors to short stature. Mutations in ~140 genes only account for about half of the 372 known subtypes of skeletal dysplasia. We are studying two recessive, spontaneous mouse mutants with skeletal dysplasia and fertility problems, peewee and chagun to identify the mutant genes, understand the mechanism of action and pathology, and explore therapeutic interventions.