Dr. Hecht is a board-certified medical geneticist with extensive clinical expertise in common birth defects and gene discovery studies in complex birth defects, including nonsyndromic cleft lip and palate, nonsyndromic clubfoot and single gene disorders such as pseudoachondroplasia, a dwarfing condition.
We have translated our gene discoveries in animal models and defined the mutational effects on the pathophysiology using next-generation technologies. For example, we have shown that genetic variation in CRISPLD2 is associated with human nonsyndromic cleft lip and palate and that perturbation of CRISPLD2 gene expression cause orofacial abnormalities in zebrafish. We continue to identify the genetic pathways in which CRISPLD2 plays a role in craniofacial development using both zebrafish and mice. We are also using next-generation technologies to identify the genetic variation contributing to clefting in families.
Our other research focuses on understanding the molecular mechanisms that contribute to the pathology that underlies pseudoachondroplasia, a dwarfing condition. We have shown that mutations in cartilage oligomeric matrix protein (COMP), a large extracellular matrix protein, are the cause of this dwarfing condition. COMP mutations cause a dominant negative effect such that the mutant protein cannot be exported into the extracellular matrix and is retained in the ER of growth plate chondrocytes. Using our transgenic MT-COMP mouse, we defined the molecular mechanisms that contribute to MT-COMP retention and are assessing therapeutic interventions to reduce the intracellular load of MT-COMP.