Clinical utility of MS molecular phenotypes of MS
My group at the Centre for Immunology aims to translate immunogenetic findings from discovery to clinical practice. We have used genome wide association studies to identify genetic variants which affect risk of multiple sclerosis, hepatitis C infection and response to drugs. We have used transcriptomic, flow cytometric and cell culture approaches to investigate why genetic variants affect the immune response. This has identified pathogenic processes which we now propose to investigate further, leveraging off the genetic findings. We are located in the new Westmead Millennium Building, co-located with the Centre for Virology and the Storr Liver Unit. Our director is Prof Graeme Stewart, and we closely collaborate with Prof Steve Vucic, who runs the MS clinic at Westmead Hospital. We also collaborate with immunologists at the Garvan Institute, nationally (eg the ANZgene consortium) and internationally (eg. the International Multiple Sclerosis Genetics Consortium). We offer 3 projects for postgraduate studies.
MS is an autoimmune disease where pathogenesis is driven by immune cells crossing the blood brain barrier and orchestrating an immune attack against the myelin sheath of oligodendrocytes. Therapies targeting immune cell subsets are the current mainstay of MS clinical management. Based on the MS risk genes, we have identified three molecular phenotypes in MS, and now propose to test their clinical utility. They may allow personalisation of therapy, monitoring of therapeutic success, or present new therapeutic options. The phenotypes are 1. RPS6hi; 2. EOMES/TBX21 low; and 3. ZMIZ1/ZFP36L2 low. The techniques utilized will be generation, curation and application of biobanks, genotyping, flow cytometry, RTPCR, methylation, cell subset sorting and culture. Projects to examine the correlation of these molecular phenotypes with clinical phenotypes, immune cell subsets, genetic variation and viral infection are suggested.
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