Hieter, Phil - University of British Columbia - Department of Biochemistry and Molecular Biology

个人简介

John Hopkins University, 1981, PhD

研究领域

The major focus of our laboratory is the molecular biology of eukaryotic chromosome transmission. Genetic and molecular approaches are used to study determinants that control the mitotic and meiotic segregation of chromosomes in the yeast Saccharomyces cerevisiae. Genetic perturbation causing a chromosome instability (CIN) phenotype in cancer cells is now widely recognized to be a major predisposing condition in cancer initiation and/or progression. S. cerevisiae has proven to be an excellent experimental organism for the study of mitotic cell division and the chromosome transmission cycle. One line of research is aimed at identifying genes that encode or regulate the function of kinetochore proteins that directly interact with centromeric DNA. A second line of research involves analysis of a large reference collection of mutants that are defective in chromosome segregation and that define genes required for kinetochore function, sister chromatid cohesion, chromosome structure, and control of cell cycle progression at mitosis. A third line of research focuses on the Anaphase Promoting Complex (APC), which acts as an E3 activity in the ubiquitination of key cell cycle regulatory proteins (eg., mitotic cyclins) that regulate transition from metaphase to anaphase and exit from mitosis. The results of our proposed research will provide a basic understanding of the mechanisms of chromosome transmission, and will therefore be directly relevant to an understanding of cancer mechanisms. The results may also be useful in developing strategies for cancer therapy and for sub-classification of tumors based on their CIN mutational spectrum.

近期论文

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Hamza A1, Tammpere E1, Kofoed M1, Keong C1, Chiang J1, Giaever G1, Nislow C1, Hieter P2. Complementation of Yeast Genes with Human Genes as an Experimental Platform for Functional Testing of Human Genetic Variants. Genetics. 2015 Sep 9. PMID: 26354769. Bailey ML1, Singh T1, Mero P2, Moffat J2, Hieter P3. Dependence of Human Colorectal Cells Lacking the FBW7 Tumor Suppressor on the Spindle Assembly Checkpoint. Genetics. 2015 Sep 8. PMID: 26354767. Kofoed M1, Milbury KL2, Chiang JH3, Sinha S3, Ben-Aroya S4, Giaever G3, Nislow C3, Hieter P5, Stirling PC6. An Updated Collection of Sequence Barcoded Temperature-Sensitive Alleles of Yeast Essential Genes. G3 (Bethesda). 2015 Jul 14;5(9):1879-87. PMID: 26175450. Hieter P1, Boycott KM2. Understanding rare disease pathogenesis: a grand challenge for model organisms. Genetics. 2014 Oct;198(2):443-5. PMID: 25316782. Chan YA1, Hieter P2, Stirling PC3. Mechanisms of genome instability induced by RNA-processing defects. Trends Genet. 2014 Jun;30(6):245-53. PMID: 24794811. Chan YA1, Aristizabal MJ2, Lu PY2, Luo Z3, Hamza A1, Kobor MS4, Stirling PC5, Hieter P6. Genome-wide profiling of yeast DNA:RNA hybrid prone sites with DRIP-chip. PLoS Genet. 2014 Apr 17;10(4):e1004288. PMID: 24743342. Li X1, O’Neil NJ1, Moshgabadi N1, Hieter P2. Synthetic cytotoxicity: digenic interactions with TEL1/ATM mutations reveal sensitivity to low doses of camptothecin. Genetics. 2014 Jun;197(2):611-23. PMID: 24653001. Huang Y1, Minaker S, Roth C, Huang S, Hieter P, Lipka V, Wiermer M, Li X. An E4 ligase facilitates polyubiquitination of plant immune receptor resistance proteins in Arabidopsis. Plant Cell. 2014 Jan;26(1):485-96. PMID: 24449689. Bailey ML1, O’Neil NJ, van Pel DM, Solomon DA, Waldman T, Hieter P. Glioblastoma cells containing mutations in the cohesin component STAG2 are sensitive to PARP inhibition. Mol Cancer Ther. 2014 Mar;13(3):724-32. PMID: 24356817. Stirling PC1, Shen Y, Corbett R, Jones SJ, Hieter P. Genome destabilizing mutator alleles drive specific mutational trajectories in Saccharomyces cerevisiae. Genetics. 2014 Feb;196(2):403-12. PMID: 24336748. Sajesh BV1, Bailey M, Lichtensztejn Z, Hieter P, McManus KJ. Synthetic lethal targeting of superoxide dismutase 1 selectively kills RAD54B-deficient colorectal cancer cells. Genetics. 2013 Nov;195(3):757-67. PMID: 24002644. Bhavsar AP1, Brown NF, Stoepel J, Wiermer M, Martin DD, Hsu KJ, Imami K, Ross CJ, Hayden MR, Foster LJ, Li X, Hieter P, Finlay BB. The Salmonella type III effector SspH2 specifically exploits the NLR co-chaperone activity of SGT1 to subvert immunity. PLoS Pathog. 2013;9(7):e1003518. PMID: 23935490. Braberg H1, Jin H, Moehle EA, Chan YA, Wang S, Shales M, Benschop JJ, Morris JH, Qiu C, Hu F, Tang LK, Fraser JS, Holstege FC, Hieter P, Guthrie C, Kaplan CD, Krogan NJ. From structure to systems: high-resolution, quantitative genetic analysis of RNA polymerase II. Cell. 2013 Aug 15;154(4):775-88. PMID: 23932120. Price JC1, Pollock LM, Rudd ML, Fogoros SK, Mohamed H, Hanigan CL, Le Gallo M, Program NI, Zhang S, Cruz P, Cherukuri PF, Hansen NF, McManus KJ, Godwin AK, Sgroi DC, Mullikin JC, Merino MJ, Hieter P, Bell DW. Sequencing of candidate chromosome instability genes in endometrial cancers reveals somatic mutations in ESCO1, CHTF18, and MRE11A. PLoS One. 2013 Jun 3;8(6):e63313. PMID: 23755103. van Pel DM1, Stirling PC, Minaker SW, Sipahimalani P, Hieter P. Saccharomyces cerevisiae genetics predicts candidate therapeutic genetic interactions at the mammalian replication fork. G3 (Bethesda). 2013 Feb;3(2):273-82. PMID: 23390603. van Pel DM1, Barrett IJ, Shimizu Y, Sajesh BV, Guppy BJ, Pfeifer T, McManus KJ, Hieter P. An evolutionarily conserved synthetic lethal interaction network identifies FEN1 as a broad-spectrum target for anticancer therapeutic development. PLoS Genet. 2013;9(1):e1003254. PMID: 23382697. O’Neil NJ1, van Pel DM, Hieter P. Synthetic lethality and cancer: cohesin and PARP at the replication fork. Trends Genet. 2013 May;29(5):290-7. PMID: 23333522. Minaker SW1, Filiatrault MC, Ben-Aroya S, Hieter P, Stirling PC. Biogenesis of RNA polymerases II and III requires the conserved GPN small GTPases in Saccharomyces cerevisiae. Genetics. 2013 Mar;193(3):853-64. PMID: 23267056. Le Gallo M1, O’Hara AJ, Rudd ML, Urick ME, Hansen NF, O’Neil NJ, Price JC, Zhang S, England BM, Godwin AK, Sgroi DC; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Hieter P, Mullikin JC, Merino MJ, Bell DW. Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes. Nat Genet. 2012 Dec;44(12):1310-5. PMID: 23104009. McLellan JL1, O’Neil NJ, Barrett I, Ferree E, van Pel DM, Ushey K, Sipahimalani P, Bryan J, Rose AM, Hieter P. Synthetic lethality of cohesins with PARPs and replication fork mediators. PLoS Genet. 2012;8(3):e1002574. PMID: 22412391. Stirling PC1, Chan YA, Minaker SW, Aristizabal MJ, Barrett I, Sipahimalani P, Kobor MS, Hieter P. R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants. Genes Dev. 2012 Jan 15;26(2):163-75. PMID: 22279048. Stirling PC1, Crisp MJ, Basrai MA, Tucker CM, Dunham MJ, Spencer FA, Hieter P. Mutability and mutational spectrum of chromosome transmission fidelity genes. Chromosoma. 2012 Jun;121(3):263-75. PMID: 22198145. Bell DW1, Sikdar N, Lee KY, Price JC, Chatterjee R, Park HD, Fox J, Ishiai M, Rudd ML, Pollock LM, Fogoros SK, Mohamed H, Hanigan CL; NISC Comparative Sequencing Program, Zhang S, Cruz P, Renaud G, Hansen NF, Cherukuri PF, Borate B, McManus KJ, Stoepel J, Sipahimalani P, Godwin AK, Sgroi DC, Merino MJ, Elliot G, Elkahloun A, Vinson C, Takata M, Mullikin JC, Wolfsberg TG, Hieter P, Lim DS, Myung K. Predisposition to cancer caused by genetic and functional defects of mammalian Atad5. PLoS Genet. 2011 Aug;7(8):e1002245. PMID: 21901109. Stirling PC1, Bloom MS, Solanki-Patil T, Smith S, Sipahimalani P, Li Z, Kofoed M, Ben-Aroya S, Myung K, Hieter P. The complete spectrum of yeast chromosome instability genes identifies candidate CIN cancer genes and functional roles for ASTRA complex components. PLoS Genet. 2011 Apr;7(4):e1002057. PMID: 21552543. Davies AH1, Barrett I, Pambid MR, Hu K, Stratford AL, Freeman S, Berquin IM, Pelech S, Hieter P, Maxwell C, Dunn SE. YB-1 evokes susceptibility to cancer through cytokinesis failure, mitotic dysfunction and HER2 amplification. Oncogene. 2011 Aug 25;30(34):3649-60. PMID: 21423216.