686 Bay Street
Toronto, ON M5G 0A4
|Lab Phone||416-813-7654, x4203|
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.
In the News
Learn more: Rotin's lab
Biochemistry and function of the Nedd4 family of ubiquitin ligases
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.
Awards & Distinctions
2004-2011 & 2011-2018 — Canada Research Chair, Tier I
2011 — Woman of Action (WOA) Scientist Award (from the Israel Cancer Research Fund, ICRF)
2003 — Zeller’s Senior Scientist Award (from the Canadian CF Foundation)
1999-2004 — CIHR Investigator
1999 — Premier’s Research Excellence Award (PREA)
1994 — Power of Dreams Research Award (from the Canadian Cf Foundation)
1993-1998 — MRC Scholarship (CIHR New Investigator)
1993 — Elsie Winifred Crann Award (from the University of Toronto)
1988-1991 — MRC Fellowship
1983-1987 — NCIC Studentship Award
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
Neuronal defects and posterior pituitary hypoplasia in mice lacking the receptor tyrosine phosphatase PTPsigma
Wallace MJ, Batt J, Fladd C, Henderson JT, Skarnes W, ROTIN D.
Nature Genet. (1999): 21: 334-8
WW domains of Nedd4 bind to the proline rich PY motifs in the epithelial Na channel deleted in Liddle’s syndrome.
Staub O, Dho S, Henry P, Correa J, Ishikawa T, McGlade J, ROTIN D
EMBO J. (1996): 15: 2371-80