[S-02] Genetic and neuropathological approach decipher the molecular mechanism of idiopathic central nervous system demyelinating diseases

[S-02-1] Susceptibility to multiple sclerosis: from genetic risk to immune dysfunction in at-risk individuals

Philip L. De Jager (Center for Translational & Computational Neuroimmunology and Multiple Sclerosis Center, Department of Neurology, Columbia University Medical Center)

Genome-wide association studies (GWAS) on multiple sclerosis (MS) in Caucasians have identified various risk genes, which are mainly related to immune functions. Molecular pathways leading to inflammatory demyelination are now becoming clearer. The first Japanese GWAS, enrolling more than 1,000 MS and neuromyelitis optica spectrum disorders (NMOSD) patients, has revealed the distinct risk genes from those in Caucasians, many of which are related to neuroglial functions. Molecular-immunopathological studies have also identified critical changes of glial cells in these conditions. Therefore, the aim of this symposium is to decipher the mechanisms of the MS and NMOSD by integrating the functions of the discovered genetic risk factors and the pathologically-proven molecular changes, with special attention on the demyelinating disorders more frequently encountered in Asians, such as NMOSD and Baló’s concentric sclerosis.

Dr. De Jager is a practicing neurologist with subspecialty training in clinical neuroimmunology and expertise in molecular biology, functional immunology, statistical genetics and computational biology. He leads data generation and the Analysis Team for national and international collaborations exploring the genetic, epigenomic, transcriptomic, and immunologic architecture of neurodegenerative diseases. The focus is the study of the inflammatory component of these diseases in studies ranging from basic susceptibility gene discovery efforts from patient materials to testing novel biometric technologies to better capture measures of patient function. Dr. De Jager recently established a new Division of Neuroimmunology in the Department of Neurology at Columbia University that brings together the clinical neuroimmunology practice with a new Center for Translational & Computational Neuroimmunology. This Center is focused on efforts to characterize and target the neuro-immunologic component of neurodegenerative diseases such as AD, MS, and PD. To execute these projects, he applies modern methods of human neuroimmunology, statistical genetics, deep quantitative neurophenotyping, single cell analyses and systems biology in studies that center on human samples from deeply characterized study participants. All projects are executed in a team-based approach with multiple local, national, and international collaborators as needed.