Description:

Naiara Aquizu, Ph.D., Assistant Professor, Department of Pathology and Laboratory Medicine and Center for Cellular and Molecular Therapeutics at CHOP and UPENN

Abstract:

Our lab studies genetic and epigenetic mechanisms of brain disorders that affect children with the ultimate goal to improve diagnosis and treatment strategies. In this talk, I will first show how our experimental work in the lab led us identify SNX13 variants as the cause of a perinatal onset spinocerebellar ataxia and intellectual disability syndrome. Furthermore, using forward genetic approaches followed by functional studies in model organisms and human pluripotent stem cells, we recently identified gain and loss of function variants in EZH1 as the basis of overlapping neurodevelopmental syndromes. While EZH1 is the underexplored catalytic member of the Polycomb Repressive Complex 2 (PRC2), its paralogue, EZH2, has well established roles in the epigenetic transmission of transcriptionally repressed programs that guarantee multicellular organism development and cellular homeostasis. Therefore, in the second part of my talk, I will show our recent work unlocking non redundant functions of EZH1 on PRC2-mediated epigenetic regulation of the nervous system development and our efforts uncovering pathogenic mechanisms and therapeutic strategies of these disorders.