CCMT Seminar Series - Nov. 28, 2022

The Raymond G. Perelman Center for Cellular and Molecular Therapeutics presents a Lecture Series:

Using Cell-Specific Epigenetics to Discover the Genetic Basis of Amyotrophic Lateral Sclerosis

Speaker

Jonathan Cooper-Knock, MD, PhD

Consultant Neurologist and Senior Lecturer

Sheffield Institute for Translational Neuroscience

University of Sheffield, UK

Description of Research

Amyotrophic lateral sclerosis (ALS) is an archetypal complex disease with a polygenic architecture. Despite high heritability, the latest ALS genome-wide association study (GWAS) identified a genetic risk factor in <10% of patients. We previously applied ATAC-seq to profile chromatin accessibility within normal motor neurons (MNs). By focusing on regulatory regions in MNs, our machine learning method reduced the search space by >90% and uncovered 690 ALS risk genes, corresponding to 35% of SNP-based heritability. In contrast to standard GWAS, we were able to identify a genetic risk factor in >50% of sporadic ALS patients. Now we are using single-cell multiome profiling of motor cortex tissue to discover ALS genetic drivers associated with the complete set of CNS cell-types.

Host

Ophir Shalem, PhD

Please email shalemo@chop.edu if you would like to meet with the speaker.