We鈥檝e moved
The Rosalind and Morris Goodman Cancer Institute can now be found at
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Ian Watson, Ph.D.
Academic title(s):
Associate Professor/Professeur Associ茅
Rosalind and Morris Goodman Cancer Institute
Department of Biochemistry
Faculty of Medicine and Health Sciences
平特五不中
Selected publications:
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- Nguyen TT, Ramsay L, Ahanfeshar-Adams M, Lajoie M, Schadendorf D, Alain T, Watson IR. Mutations in the IFN纬-JAK-STAT Pathway Causing Resistance to Immune Checkpoint Inhibitors in Melanoma Increase Sensitivity to Oncolytic Virus Treatment. Clinical Cancer Research. 2021 Jun 15;27(12):3432-3442. doi: 10.1158/1078-0432.CCR-20-3365. Epub 2021 Feb 16.
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- Alkallas R, Lajoie M, Moldoveanu D, Hoang KV, Lefrancois P, Lingrand M, Ahanfeshar-Adams M, Watters K, Spatz A, Zippin JH, Najafabadi HS, Watson IR. Multi-omic analysis reveals new driver mutations and a sex-specific tumor suppressor in cutaneous melanoma. Nature Cancer 1, 635鈥�652 (2020).听.
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- Dankner M, Lajoie M, Moldoveanu D, Nguyen TT, Savage P, Rajkumar S, Huang X, Lvova M, Protopopov A, Vuzman D, Hogg D, Park M, Guiot MC, Petrecca K, Mihalcioiu C, Watson IR, Siegel PM, Rose AAN. Dual MAPK inhibition is an effective therapeutic strategy for a subset of class II BRAF mutant melanoma. Clinical Cancer Research. 2018 Dec 15;24(24):6483-6494. doi: 10.1158/1078-0432.CCR-17-3384. Epub 2018 Jun 14.
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- Dankner M, Rose AAN, Rajkumar S, Siegel PM, Watson IR. Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations. Oncogene. 2018 Jun;37(24):3183-3199. doi: 10.1038/s41388-018-0171-x. Epub 2018 Mar 15. *Corresponding author
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- Somasundaram R, Zhang G, Fukunaga-Kalabis M, Perego M, Krepler C, Xu X, Wagner C, Hristova D, Zhang J, Tian T, Wei Z, Liu Q, Garg K, Griss J, Hards R, Maurer M, Hafner C, Mayerh枚fer M, Karanikas G, Jalili A, Bauer-Pohl V, Weihsengruber F, Rappersberger K, Koller J, Lang R, Hudgens C, Chen G, Tetzlaff M, Wu L, Frederick DT, Scolyer RA, Long GV, Damle M, Ellingsworth C, Grinman L, Choi H, Gavin BJ, Dunagin M, Raj A, Scholler N, Gross L, Beqiri M, Bennett K, Watson I, Schaider H, Davies MA, Wargo J, Czerniecki BJ, Schuchter L, Herlyn D, Flaherty K, Herlyn M, Wagner SN. Tumor-associated B-cells induce tumor heterogeneity and therapy resistance. Nature Communications. 2017 Sep 19;8(1):607. doi: 10.1038/s41467-017-00452-4.
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- Rose AA, Annis MG, Frederick DT, Biondini M, Dong Z, Kwong LN, Chin L, Keler T, Hawthorne T, Watson IR, Flaherty KT, Siegel PM. MAPK Pathway Inhibitors Sensitize BRAF Mutant Melanoma to an Antibody-Drug Conjugate Targeting GPNMB. Clinical Cancer Research. 2016 Dec 15;22(24):6088-6098. doi: 10.1158/1078-0432.CCR-16-1192. Epub 2016 Aug 11.
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- Rajkumar S. and Watson IR. (2016). Molecular characterisation of cutaneous melanoma: creating a framework for targeted and immune therapies. British Journal of Cancer. 2016 Jul 12;115(2):145-55. doi: 10.1038/bjc.2016.195. *Corresponding author.
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- Cancer Genome Atlas Research Network*. Comprehensive Genomic Characterization of Cutaneous Melanoma. Cell. 2015 Jun 18;161(7):1681-96. doi:10.1016/j.cell.2015.05.044. *Co-corresponding authors and project co-Chairs: *Ian R. Watson, Jeffrey E. Gershenwald, Lynda Chin.
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Current research:
Melanoma is the deadliest form of skin cancer. Detected in its earliest stages, melanoma is highly curable; however, the 5-year survival rate declines drastically for regional and distant metastatic disease. Recently, melanoma has emerged as the latest success story for both genomics- and immune-guided targeted therapy. Cutaneous melanoma is characterized by hotspot mutations in the mitogen-activated protein kinase (MAPK) regulators, BRAF and NRAS, found in approximately 50% and 25% of patients, respectively. The identification of these oncogenic mutations has led to the development of small molecule inhibitors targeting MAPK kinase kinases (MEK) and BRAF in melanoma. Although antitumor responses to MAPK targeted therapies have been dramatic, they are rarely durable. Furthermore, novel therapies targeting inhibitory immune checkpoint proteins have recently shown impressive clinical efficacy; nevertheless, biomarkers that predict response remain unclear.
For the past four years, I have led a number of multi-institutional collaborations (Hodis, Watson et al., 2012 Cell), which include The Cancer Genome Atlas project (TCGA, 2015 Cell), to characterize the melanoma genome and perform integrative analysis with multiple data platforms at the DNA, RNA, and protein levels. Our work has identified a number of novel significantly mutated genes in melanomas, which possess hotspot mutations in coding and non-coding regions. Based on the frequency and correlation of the most frequently significantly mutated genes, we established a framework for genomic classification into one of four subtypes: mutant BRAF, RAS, NF1, and Triple-WT (wild-type) melanomas.
In an attempt to improve on the current diagnostic and treatment modalities employed in the clinic, my lab will address the following questions:
What is the biological function and therapeutic relevance of novel significantly mutated genes discovered in our melanoma genome- and exome-sequencing studies?听
How can we target melanomas lacking BRAF and RAS hotspot mutations and prioritize such strategies in the context of immunotherapies?听
What are the mechanisms that mediate response and resistance to MAPK-targeted and immunotherapy?
To tackle these problems, my lab will employ computational approaches,听in vivo听models and biochemical techniques studying patient samples, cell lines, and melanoma mouse models.