John McPherson
Ontario Institute for Cancer Research
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Publication
Featured researches published by John McPherson.
The EMBO Journal | 2004
John McPherson; Laura Tamblyn; Andrew Elia; Eva Migon; Amro Shehabeldin; Elzbieta Matysiak-Zablocki; Bénédicte Lemmers; Leonardo Salmena; Anne Hakem; Jason Fish; Farah Kassam; Jeremy A. Squire; Benoit G. Bruneau; M. Prakash Hande; Razqallah Hakem
The Drosophila melanogaster warts/lats tumour suppressor has two mammalian counterparts LATS1/Warts‐1 and LATS2/Kpm. Here, we show that mammalian Lats orthologues exhibit distinct expression profiles according to germ cell layer origin. Lats2−/− embryos show overgrowth in restricted tissues of mesodermal lineage; however, lethality ultimately ensues on or before embryonic day 12.5 preceded by defective proliferation. Lats2−/− mouse embryonic fibroblasts (MEFs) acquire growth advantages and display a profound defect in contact inhibition of growth, yet exhibit defective cytokinesis. Lats2−/− embryos and MEFs display centrosome amplification and genomic instability. Lats2 localizes to centrosomes and overexpression of Lats2 suppresses centrosome overduplication induced in wild‐type MEFs and reverses centrosome amplification inherent in Lats2−/− MEFs. These findings indicate an essential role of Lats2 in the integrity of processes that govern centrosome duplication, maintenance of mitotic fidelity and genomic stability.
Genome Integrity | 2010
Helena Sumantrai Mistry; Laura Tamblyn; Hussein Butt; Daniel Sisgoreo; Aileen Gracias; Meghan Larin; Kalpana Gopalakrishnan; Manoor Prakash Hande; John McPherson
BackgroundDNA double-strand breaks (DSBs) caused by ionizing radiation or by the stalling of DNA replication forks are among the most deleterious forms of DNA damage. The ability of cells to recognize and repair DSBs requires post-translational modifications to histones and other proteins that facilitate access to lesions in compacted chromatin, however our understanding of these processes remains incomplete. UHRF1 is an E3 ubiquitin ligase that has previously been linked to events that regulate chromatin remodeling and epigenetic maintenance. Previous studies have demonstrated that loss of UHRF1 increases the sensitivity of cells to DNA damage however the role of UHRF1 in this response is unclear.ResultsWe demonstrate that UHRF1 plays a critical role for facilitating the response to DSB damage caused by γ-irradiation. UHRF1-depleted cells exhibit increased sensitivity to γ-irradiation, suggesting a compromised cellular response to DSBs. UHRF1-depleted cells show impaired cell cycle arrest and an impaired accumulation of histone H2AX phosphorylation (γH2AX) in response to γ-irradiation compared to control cells. We also demonstrate that UHRF1 is required for genome integrity, in that UHRF1-depleted cells displayed an increased frequency of chromosomal aberrations compared to control cells.ConclusionsOur findings indicate a critical role for UHRF1 in maintenance of chromosome integrity and an optimal response to DSB damage.
Cancer Letters | 2016
Alyssa L. Smith; Najmeh Alirezaie; Ashton A. Connor; Michelle Chan-Seng-Yue; Robert Grant; Iris Selander; Claire Bascuñana; Ayelet Borgida; Anita Hall; Thomas Whelan; Spring Holter; Treasa McPherson; Sean P. Cleary; Gloria M. Petersen; Atilla Omeroglu; Emmanouil Saloustros; John McPherson; Lincoln Stein; William D. Foulkes; Jacek Majewski; Steven Gallinger; George Zogopoulos
The genetic basis underlying the majority of hereditary pancreatic adenocarcinoma (PC) is unknown. Since DNA repair genes are widely implicated in gastrointestinal malignancies, including PC, we hypothesized that there are novel DNA repair PC susceptibility genes. As germline DNA repair gene mutations may lead to PC subtypes with selective therapeutic responses, we also hypothesized that there is an overall survival (OS) difference in mutation carriers versus non-carriers. We therefore interrogated the germline exomes of 109 high-risk PC cases for rare protein-truncating variants (PTVs) in 513 putative DNA repair genes. We identified PTVs in 41 novel genes among 36 kindred. Additional genetic evidence for causality was obtained for 17 genes, with FAN1, NEK1 and RHNO1 emerging as the strongest candidates. An OS difference was observed for carriers versus non-carriers of PTVs with early stage (≤IIB) disease. This adverse survival trend in carriers with early stage disease was also observed in an independent series of 130 PC cases. We identified candidate DNA repair PC susceptibility genes and suggest that carriers of a germline PTV in a DNA repair gene with early stage disease have worse survival.
Clinical Chemistry | 2009
Eleftherios P. Diamandis; Karl V. Voelkerding; Rade Drmanac; David B. Agus; John McPherson
In 1980, Fred Sanger and Walter Gilbert were awarded the Nobel Prize in Chemistry for discovering novel ways for sequencing nucleic acids. In 2003, the human genome sequence was published, an effort that involved more than 3000 scientists from 6 countries. The work took 13 years to complete, at a cost of nearly
Bioinformatics | 2014
Carson Holt; Bojan Losic; Deepa Pai; Zhen Zhao; Quang Trinh; Sujata Syam; Niloofar Arshadi; Gun Ho Jang; Johar Ali; Tim Beck; John McPherson; Lakshmi Muthuswamy
3 billion. Only 6 years later, nucleic acid sequencing technologies have advanced to a stage in which a human genome can be sequenced within weeks at a cost of
Toxicological Sciences | 2012
Stephanie L. Ondovcik; Laura Tamblyn; John McPherson; Peter G. Wells
50 000 or less. These new sequencing technologies are about a million times more efficient than standard Sanger sequencing. Now, people are talking about the
Cell Reports | 2017
Mauricio Medrano; Laudine Communal; Kevin R. Brown; Marcin P. Iwanicki; Josee Normand; Joshua Paterson; Fabrice Sircoulomb; Paul M. Krzyzanowski; Marian Novak; Sasha A. Doodnauth; Fernando Suarez Saiz; Jane Cullis; Rima Al-awar; Benjamin G. Neel; John McPherson; Ronny Drapkin; Laurie Ailles; Anne Marie Mes-Massons; Robert Rottapel
1000 genome, and there is an X Prize worth
Toxicology and Applied Pharmacology | 2013
Stephanie L. Ondovcik; Laura Tamblyn; John McPherson; Peter G. Wells
10 million for sequencing 100 human genomes within 10 days at a cost of <
Cancer Research | 2016
Michael Fraser; Theodorus van der Kwast; John McPherson; Colin C. Collins; Yves Fradet; Bernard Têtu; Alain Bergeron; Robert G. Bristow; Paul C. Boutros
10 000 per genome. International organizations are sequencing thousands of cancer genomes to find novel genetic changes, and individuals with money are paying for genomewide association studies in hopes of preventing diseases to which they are predisposed. Although the technologies for high-throughput sequencing are here and although they are being perfected in terms of accuracy and reduced costs, many questions are being raised. Some of these questions are explored below with leading scientists from academia and industry. Karl V. Voelkerding2 : Calculating the cost for sequencing a human genome needs to incorporate the level of sequencing “completeness” or “coverage” that will be required to accurately characterize both sequence and structural variation. Reagent and wet bench labor costs for sequencing a human genome should approach
Cancer Research | 2016
Syed H. Zaidi; Catie Grasso; Jasmine Mu; Eve Shinbrot; Marios Giannakis; Charles Connolly; Ivan Borozan; Hermann Brenner; Peter T. Campbell; Andrew T. Chan; Jenny Chang-Claude; Mengmeng Du; Vincent Ferretti; Amy J. French; Charles S. Fuchs; Steven Gallinger; Levi A. Garraway; Andrea Gsur; Marc J. Gunter; Tabitha A. Harrison; Michael Hoffmeister; Li Hsu; Wen-Yi Huang; Jeroen R. Huyghe; Mathieu Lemire; Elaine R. Mardis; John McPherson; Polly A. Newcomb; Lincoln Stein; Wei Sun
5000 or less within three to five years, depending on the technology. It is difficult to price the costs for bioinformatic analysis, currently a lengthy and extensive process that varies depending on the questions being asked. New computational algorithms will definitely streamline this process. Beyond …