Our laboratory is interested in understanding fundamental mechanisms of transcription and RNA splicing in the nervous system, and how these mechanisms bear on neuronal connectivity and neurodegenerative diseases. Interest in neuronal connectivity arose from our discovery of a remarkable organization of a large cluster of genes encoding cell surface cadherin-like proteins called protocadherins. This unusual gene organization leads to the generation of enormous individual cell surface diversity at the synapse through a mechanism that involves stochastic promoter choice and alternative RNA splicing. We are studying the detailed mechanisms of promoter choice, and are using gene knock out methods to investigate the function of protocadherins. We are also using embryonic stem cell differentiation and deep sequencing methods to study transcription, RNA splicing, protein-RNA interactions, and microRNAs in ALS disease models. This involves studies of SOD1, FUS and TDP43 mouse models, and human patient derived iPS cells. Our current focus is in understanding the role of astrocyte/motor neuron interactions in ALS disease mechanisms. In addition, we are interested in the role of the immune system in ALS, and are investigating the role of microglia in ALS disease mechanisms.
Ye,J., Chen, S. and Maniatis, T.
Cardiac glycosides are potent inhibitors of interferon-beta gene expression. Nature Chem. Biol. 7(1):25-33. (2011)
Schalm S.S., Ballif B.A., Buchanan S.M., Phillips G.R., and Maniatis T.
Phosphorylation of protocadherin proteins by the receptor tyrosine kinase Ret. Proc Natl Acad Sci U S A. 107(31):13894-9-. (2010)
Chiu I.M., Phatnani H., Kuligowski M., Tapia J.C., Carrasco M.A., Zhang M., Maniatis T., and Carroll M.C.
Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice. Proc Natl Acad Sci U S A. 106(49):20960-5. (2009)
Di Giorgio F.P., Carrasco M.A., Siao M.C., Maniatis T., and Eggan K.
Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci. 10(5):608-14. (2007)
Makeyev E.V., Zhang J., Carrasco M.A., and Maniatis T.
The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell. 3 27(3):435-48. (2007)