SUBJECT: | Ph.D. Proposal Presentation |
BY: | Liana Hatoum |
TIME: | Tuesday, January 17, 2023, 10:30 a.m. |
PLACE: | Whitaker Ford Building, 3115 |
TITLE: | Longitudinal Magnetic Resonance Angiography to Quantify Arterial Remodeling in Sickle Cell Disease |
COMMITTEE: | Dr. Manu O. Platt, Chair (BME) Dr. Edward A. Botchwey (BME) Dr. Spencer H. Bryngelson (College of Computing) Dr. Rudolph L. Gleason (ME) Dr. John N. Oshinski (BME) Dr. Alessandro Veneziani (Mathematics, Emory) |
SUMMARY
Sickle cell disease (SCD) is a genetic blood disorder affecting 100,000 Americans. People living with SCD experience deteriorating disease progression with accelerated damage to carotid and cerebral arteries occurring as early as 2 years old. 11% of children with SCD suffer an overt stroke and 37% will suffer a silent stroke. Hematopoietic stem cell transplant (HSCT) is currently the only known cure for SCD. Children may continue to be at risk for strokes and other complications after HSCT. The pathogenesis of how arterial damage is initiated, and progresses is not fully understood. Recent studies have shown using a humanized sickle cell transgenic mouse model that cathepsin K, a powerful protease, is upregulated in SCD and mediates elastin and collagen degradation in the arterial wall. In those studies, expansive remodeling was observed in the common carotid arteries associated with aneurysms and weakened artery mechanics. The central hypothesis of this proposal is that chronic inflammation in SCD stimulates cathepsin K overexpression leading to pathological expansive arterial remodeling that can cause accelerated progression of aneurysms and hemorrhagic strokes. |