SUMMARY
Ethylin W. Jabs, M.D., focuses on clinical and molecular research concerning genomic conditions such as structural craniofacial and limb anomalies. Her research team has elucidated the phenotype and genotype for more than 50 rare or complex conditions including the identification of mutations in homeobox and helix-loop-helix transcription factors, fibroblast growth factor receptors, and connexins. These studies reveal the pathogenetic mechanisms of these mutations.
Dr. Jabs' research finds signaling pathways, expression and regulatory networks involved in regular or unusual developmental processes as well as phenotype-genotype correlations. Based on these findings, therapeutic strategies are being evaluated in mouse models.
Focus areas
- Genomics of craniosynostosis. Dr. Jabs' research increases understanding of the molecular basis of craniosynostosis, which is the premature fusion of skull bones that can lead to secondary neurological conditions. She performs whole-genome sequencing in individuals with craniosynostosis and identifies pathogenetic variants. Dr. Jabs develops mouse models with these variants and studies the impact of dysmorphology, the transcriptome and the proteome in the developing skull in vivo.
- Genomics of oral clefting. Dr. Jabs created a biobank of samples from people with malformation syndromes. She collaborated with her colleagues extensively to identify the molecular basis of oral clefting including cleft lip with or without cleft palate, mandibulofacial dysostosis, and Pierre Robin complex. Dr. Jabs' research team works to elucidate the temporospatial processes involved in the development of these craniofacial features and the contribution of irregular signaling in the epithelium and mesenchyme of the developing oral complex.
- Genomics of genetic limb conditions. Dr. Jabs studies limb reduction in a cohesinopathy mouse model of Roberts syndrome. Her research group found that the irregular limb development is mediated by p53-dependent cell cycle arrest, DNA damage, cell death and an inflammatory leukotriene signaling pathway that culminates with vascular disruption. Treatment with pifithrin-alpha, a p53 inhibitor, decreased hemorrhage in affected limbs. Among the genes involved in the pathogenetic process, there is enrichment for genes implicated in thalidomide embryopathy and other genetic limb reduction conditions suggesting an underlying vascular etiology among these conditions.
Significance to patient care
Facial and limb differences can have significant physical, psychosocial and financial burdens for individuals and their families. Research in understanding the genetic causes of these conditions provides information to develop genetic diagnostic testing for these conditions and insights to guide medical and surgical management and treatment.
Professional highlights
- Chair, Department of Clinical Genomics, Mayo Clinic, 2023-present.
- Icahn School of Medicine at Mount Sinai, New York:
- Adjunct professor of genetics and genomic sciences, 2023-present.
- Professor of developmental genetics, 2018-2023.
- Adjunct professor of genetic medicine, Johns Hopkins University, Baltimore, Maryland, 2019-present.
- Member, Johns Hopkins Society of Scholars, 2014.
- Member, Association of American Physicians, 2011.
- Member, American Society for Clinical Investigation, 1995.