Dysfunctional RNA binding proteins in MS

The long-term goal of research in the Levin Lab is to better understand the cause of neurodegeneration, a salient feature and cause of permanent disability in progressive multiple sclerosis (MS) patients. For more than 20 years, we have studied the function of the RNA binding protein heterogeneous nuclear ribonuclearprotein A1(hnRNP A1-‘A1’), with a focus on ‘M9’. M9 is A1’s nucleocytoplasmic transport domain and is required for transport of A1 between the nucleus and cytoplasm. Our lab has discovered that MS patients make antibodies to M9 and the brains and lymphocytes of MS patients contain somatic DNA mutations within M9. Using a number of molecular, invitro and invivo techniques, our data indicates that DNA  mutations within M9 and autoimmunity to M9 result in A1 dysfunction and subsequent neuronal and axonal degeneration. Using this model, we examine potential mechanisms of neurodegeneration in MS resulting from A1 dysfunction.