Thomas Peter Maniatis

I am interested in connecting basic science with the understanding of disease mechanisms.  This interest started with our studies of globin genes in the 1980s, when we developed and applied gene cloning approaches to identify mutations that cause the genetic disease b-thalassaemia.  This work led to the first identification of single base mutations that cause RNA splicing defects.  Our work on interferon gene expression led to the discovery of the role of the ubiquitin-proteosome pathway in the activation of interferon expression.  This led to the development of proteosome inhibitors to treat cancer.  Our current efforts are directed towards understanding the role of single cell diversity in brain wiring in our studies of the protocadherin gene cluster.  Sequence variants in this gene cluster have been implicated in genetic studies of autism by others. Finally, we have taken genetic and genomic approaches to the study of disease mechanisms in the neurodegenerative disease ALS (or Lou Gherig's disease).  This has led to a focus on the role of neuroinflammation in the disease.