个人简介

BSc University of British Colubmia PhD Pharmacology, University of Alberta PDF Molecular Evolution, State University of New York

研究领域

High-throughput DNA Sequencing, Genomics

The main focus in our lab (located at the BC Cancer Agency Genome Sciences Centre) is understanding and potentiating the anti-cancer immune response. Increasingly cancer is being seen as a disease of immune failure, and in the field considerable effort is being focused on evoking and/or potentiating anti-tumor immunity. In our group, we are taking many approaches in both patient and animal studies to isolate and expand tumor-specific T cells, and to genetically engineer them for improved efficacy. We also develop high-throughput genomic, proteomic and bioinformatic methods to probe the cellular immune system, with a focus on antigen discovery. In addition to immunology, we also touch on aspects of microbiome research, brain research and evolutionary biology in our group.

近期论文

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Brown SD, Hapgood G, Steidl C, Weng AP, Savage KJ, Holt RA. Defining the clonality of peripheral T cell lymphomas using RNA-seq. Bioinformatics 2016 December Martin SD, Brown SD, Wick DA, Nielsen JS, Kroeger DR, Twumasi-Boateng K, Holt RA, Nelson BH. Low mutation burden in ovarian cancer may limit the utility of neoantigen-targeted vaccines. PloS one. 2016 May 18;11(5):e0155189 Brown SD, Raeburn LA, Holt RA. Profiling tissue-resident T cell repertoires by RNA sequencing. Genome Medicine. 2015 Nov 30;7(1):125 Holt RA. Immunogenomics: a foundation for intelligent immune design. Genome Medicine. 2015 Nov 19;7(1):116 The Cancer Genome Atlas Research Network. Genomic Classification of Cutaneous Melanoma. Cell. 2015 Jun 18;161(7):1681-96 Gibb EA, Warren RL, Wilson GE, Brown SD, Robertson G, Morin GB and Holt RA. Activation of an endogenous retrovirus-associated long non-coding RNA in human adenocarcinoma. Genome Medicine. 2015 Mar 5;7(1):22. Sharma G and Holt RA. T-cell epitope discovery technologies. Human Immunology. 2014 Jun;75(6):514-519. Brown SD, Warren RL, Gibb E, Martin SD, Nelson BH, Holt RA. Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Research. 2014 May;24(5):743-50. PMID: 24782321. Wick D, Webb JR, Nielsen JS, Martin S, Kroeger DR, Milne K, Castellarin M, Twumasi-Boating K, Watson PH, Holt RA, Nelson BH. Surveillance of the tumor mutanome by T cells during progression from primary to recurrent ovarian cancer. Clinical Cancer Research. 2014 Mar 1;20(5):1125-34. Woodsworth DJ, Castellarin M, Holt RA. Sequence analysis of T-cell repertoires in health and disease. Genome Medicine. 2013 Oct 30;5(10):98. Watson CT, Steinberg KM, Huddleston J, Sudmant P, Warren RL, Malig M, Schein J, Willsey JA, Joy JB, Scott JK, Graves, Wilson RK, Holt RA, Eichler EE, Breden F. Complete haplotype sequence of the human immunoglobulin heavy-chain variable, diversity, and joining genes and characterization of allelic and copy-number variation. American Journal of Human Genetics. 2013 Apr 4;92(4):530-46. Warren RL, Choe G, Freeman DJ, Castellarin M, Munro S, Moore R, Holt RA. Derivation of HLA types from shotgun sequence datasets. Genome Medicine. 2012 Dec 10;4(12):95. Castellarin M, Milne K, Zeng T, Tse K, Mayo M, Zhao YJ, Webb JR, Watson PH, Nelson BH, Holt RA. Clonal evolution of high-grade serous ovarian carcinoma from primary to recurrent disease. Journal of Pathology. 2013 March 229(4):515-524 The Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012 Jul 18; 478(7407):330-7. Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, Barnes R, Watson P, Allen-Vercoe E, Moore RA, Holt RA. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Research. 2012 Feb;22(2):299-306. Moore RA, Warren RL, Freeman JD, Gustavsen JA, Chenard C, Friedman JM, Suttle CA, Zhao Y, Holt RA. The sensitivity of massively parallel sequencing for detecting candidate infectious agents associated with human tissues. PLoS One. 2011;6(5):e19838. Warren RL, Freeman JD, Zeng T, Choe G, Munro S, Moore R, Webb JR, Holt RA. Exhaustive T- cell repertoire sequencing of human peripheral blood samples reveals signatures of antigen selection and a directly measured repertoire size of at least 1 million clonotypes. Genome Research. 21(5):790-7. 2011 Gardy JL et al. Whole Genome Sequencing and Social Network Analysis of a Tuberculosis Outbreak. New England Journal of Medicine. 364(8):730-9. 2010 Jones SJM et al. Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors. Genome Biology. 9;11(8):R82. 2010 Mead CL, Kuzyk MA, Moradian A, Wilson GM, Holt RA, Morin GB. Cytosolic protein interactions of the schizophrenia susceptibility gene dysbindin. Journal of Neurochemistry. 113(6):1491-1503. 2010