Jimmy Holder, PhD, MD

I am a physician-scientist and neurogeneticist specializing in profound neurodevelopmental disorders. My work spans bench research focusing on regulatory mechanisms of neurodevelopmental disorder causing genes, deep clinical phenotyping and therapeutic clinical trials for neurodevelopmental disorders. My lab focuses on the post-translational regulation of SHANK3 protein stability. Haploinsufficiency of SHANK3 causes the profound neurodevelopmental disorder Phelan-McDermid syndrome. While multiple approaches have been proposed to boost SHANK3 abundance, our group has focused on discovering the molecular regulation of SHANK3 protein stability as a therapeutic entry point. We have proposed that this approach could be generalizable for dosage sensitive genes.

My clinical research focuses on deep phenotyping developmental synaptopathies including Phelan-McDermid syndrome and SYNGAP1-Related Disorder, now through the Developmental Synaptopathy Consortium. I have served as a site PI for multiple therapeutic clinical trials including three for Phelan-McDermid syndrome and one for Sanfilippo syndrome using a genetic medicine.