Rotin, Daniela - University of Toronto - Department of Biochemistry

个人简介

Daniela Rotin completed her PhD with Dr. Ian Tannock at the Ontario Cancer Institute, Toronto, followed by two Postdoctoral Fellowships, first at the Hospital for Sick Children, Toronto, with Dr. Sergio Grinstein, working on ion transport, and then with Dr. Joseph Schlessinger in NYU Medical Center in NY, working on Signal Transduction. She has been an Independent Investigator at the Cell Biology Program, the Hospital for Sick Children , Toronto, since 1992, where she is now a Senior Scientist, as well as a Professor at the Biochemistry Department, University of Toronto.

研究领域

My laboratory has been studying the ubiquitin system, particularly the Nedd4 family of E3 ubiquitin ligases. We are studying the biochemistry, structure and function of these E3 ligases, as well as their physiological functions using cells and model organisms. Moreover, we have developed proteomic methodologies to globally identify substrates for E3 ubiquitin ligases and have subsequently focused our studies on some of the membrane proteins that were identified in these screens (eg the sodium channel ENaC, the FGF receptor, and several others). These studies are relevant to human diseases such as hypertension, cystic fibrosis (CF) and cancer.Other related project in the lab focus on two other membrane proteins: CFTR, the protein that is mutated in CF, for which we are developing assays and small molecules that can rescue the major mutation in this disease, and PTPsigma, a tyrosine phosphatase that malfunctions in Inflammatory Bowel Disease.

近期论文

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Tyrosine phosphorylation of Nedd4-1 activates its ubiquitin ligase activity Persaud A, Alberts P, Mari S, Tong J, Murchie R, Maspero E, Safi F, Moran MF, Polo S, ROTIN D. Science Signal. (2014) Oct; 7: ra95 Protein tyrosine phosphatase σ targets apical junction complex proteins in the intestine and regulates epithelial permeability Murchie R, Guo CH, Persaud A, Muise A, ROTIN D Proc. Natl. Acad. Sci. USA (2014) Jan 14; 111: 2: 693-8. Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function Persaud A, Alberts P, Hayes M, Guettler S, Clarke I, Sicheri F, Dirks P, Ciruna B, ROTIN D. EMBO J. (2011) Jul 15; 30: 16: 3259-73 Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like disease. Kimura T, Kawabe H, Jiang C, Zhang W, Xiang YY, Lu C, Salter MW, Brose N, Lu WY, ROTIN Proc. Natl. Acad. Sci. USA (2011) Feb 22; 108: 8: 3216-21 Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays Persaud A, Alberts P, Amsen EM, Xiong X, Wasmuth J, Saadon Z, Fladd C, Parkinson J, ROTIN D Mol. Syst. Biol. (2009) Dec 1; 5: 333. Physiological functions of the HECT family of ubiquitin ligases ROTIN D and Kumar S. Nat. Rev. Mol. Cell Biol. (2009) June; 10: 6: 398-409. Use of kinase inhibitors to correct ΔF508-CFTR function Trzcinska-Daneluti AM, Nguyen L, Jiang C, Fladd C, Uehling D, Prakesch M, Al-awar R, ROTIN D. Mol. Cell. Proteomics (2012) Sep; 11: 9: 745-57 Protein Tyrosine Phosphatase sigma is associated with Ulcerative Colitis. Muise A, Walters T, Wine E, Griffiths A, Duerr R, Turner D, Regueiro M, Ngan BY, Sherman P, Siverberg M, ROTIN D. Curr. Biol. (2007): 17: 1212-18