The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Pediatrics
School of Dentistry
Associate Dean for Research
These studies focus on identifying genes contributing to nonsyndromic cleft lip and palate (NSCLP) and nonsyndromic clubfoot, which are two common birth defects. These birth anomalies affect 1/1000 live births, 4,000 newborns in Texas and 135,000 worldwide per year and are associated with significant morbidity. Very little is known about the etiology but we have shown that they have a genetic component. We are using GWAS, sequencing and functional approaches in a family-based dataset to identify the genetic variation underlying these birth anomalies. The results may allow development of screening strategies to identify individuals at high risk to have affected children.
These studies focus on understanding how mutations in cartilage specific genes affect cartilage and linear bone growth. We have previously demonstrated that mutations in cartilage oligomeric matrix protein (COMP) cause two dwarfing conditions, pseudoachondroplasia and multiple epiphyseal dysplasia. COMP is a large extracellular matrix protein whose function is unknown. We have shown that COMP mutations have a dominant negative effect on protein folding such that the mutant protein cannot be exported into the extracellular matrix. We have generated a transgenic MT-COMP mouse and have defined the natural history of the chondrocyte pathology and shown that cellular stress is greatly increased. We are using FDA approved drugs to reduce cellular stress mechanisms. Our preliminary studies are encouraging as reduced cellular stress allows for export of COMP into the extracellular matrix.
Education & Training
Ph.D. - The University of Texas School of Public Health at Houston - 1988