Rose-Mary Boustany
I completed medical school/pediatric residency at the American University of Beirut Medical Center (AUBMC), Adult/Pediatric Neurology/Neurogenetics/Neurochemistry at Mass General Hospital, moving to Duke in ‘88 to Pediatrics/Neurology/Genetics/Genome Science/Cellular & Molecular Biology. Still a Duke Adjunct Professor of Pediatrics. My focus is advancing clinical/basic knowledge in neurogenetic disorders. Returned ‘06 to AUBMC to train scientists/physician-scientists, enhance capacity building as Chair of Abuhaidar Neuroscience Institute/Chair, Psychiatry establishing pediatric psychiatry/inpatient psych/neuro-ICU/microarray units at AUBMC. Presently, Division Chief, Pediatric Neurology/Director of Neurogenetics & Professor of Pediatrics/Adolescent Medicine, Biochemistry/Molecular Genetics & founder of the AUBMC Special Kids Clinic. I helped identify 3 NCL genes, uncovered apoptosis/dysregulated sphingolipid trafficking as mechanisms of neurodegeneration in CLN3 disease; CLN3 overexpression as biomarker for cancer; established flupirtine as neuroprotective in NCL cells & CLN3-/- post-mitotic neurons; an anterograde defect in galactosylceramide transfer to lipid rafts in CLN3 disease treating Cln3 Δex7/8 knock-in mice; confirmed high ceramide in CLN3/CLN2 brain & defined molecular impact of CLN3 expression in vitro on cell ceramide/cell death; defined a conserved motif 291VYFAE295 as antiapoptotic & as a structural galactosylceramide lipid raft binding domain. Also, determined anterograde GalCer trafficking as impaired in CLN3-deficient cells with GalCer deficit increasing ceramide/promoting apoptosis. We established that GalCer diminished apoptosis in vitro/vivo lowering ceramide. We proved elevated expression of CLN3 mRNA/protein in cancer cell lines/in colon & breast cancer in Lebanon. We confirmed antiapoptotic flupirtine maleate as neuroprotective in NCL cells & a Cln3 knock-in mouse abrogating apoptosis/lowering ceramide & improving neurological behavior. Presently exploring impact of other flupirtine maleate derivatives as treatment for CLN3/CLN6 disease. Over the past few years have identified a series of novel autism genes specific for the Lebanese population.
Abstracts this author is presenting: