DENNIS HAZELETT LABORATORY

Originally trained as a geneticist in the field of developmental biology, I have a broad background in both experimental and computational biology. I rely on a systems-biology approach involving the analysis and synthesis of next-generation sequencing data. My most recent contributions are highlighted by efforts to annotate and draw inference from the functional consequences of genetic associations from genome-wide association studies (GWAS) for prostate cancer, Hodgkins lymphoma and ovarian cancers. Toward this goal, I integrated GWAS and next-generation sequencing data from my collaborators with public datasets such as1000 genomes and the Encyclopedia of DNA elements (ENCODE) to infer new diseases variants outside of transcribed sequences. I have recently begun independent efforts as a principle investigator at Cedars-Sinai Medical Center, using novel approaches to achieve a greater understanding of the relationship between the regulatory code and genetic disease variants.

SIMON COETZEE

 Research Bioinformatician II

I began my career doing bioinformatics analysis of GWAS data as part of the U19 GAME-ON consortium at USC. Since then, I have focused on the functional consequences of non-protein coding risk regions within the context of many complex diseases. To this end, we developed a software program called FunciSNP, which is an R/Bioconductor tool integrating functional non-coding datasets with genetic association studies to identify candidate regulatory SNPs (Coetzeeet al., 2012). I have worked on analyzing and interpretation of large genomic datasets, including next-generation sequencing from internal collaborations and downloaded from public datasets such as 1000 genomes, The Encyclopedia of DNA Elements (ENCODE), NIH Epigenomics Roadmap, and The Cancer Genome Atlas. At Cedars-Sinai, I am working with Dr. Ben Berman and Dr. Dennis Hazelett to develop automation tools for analysis and functional annotation of genetic variants from large genome and epigenome sequencing projects. I am also continuing my development of novel algorithms for the analysis of gene regulatory sequences

PUBLICATIONS

Bauer H, Meier A, Hild M, Stachel S Economides A, Hazelett D, Harland RM, Hammershchmidt M: Follistatin and Noggin are excluded from the zebrafish organizer. Dev Biol 1998 vol. 204 pp. 488-507. PMID: 9882485

Hazelett DJ, Bourouis M, Walldorf U, Treisman JE: decapentaplegic and wingless are regulated by eyes absent and eyegone and interact to direct the pattern of retinal differentiation in the eye disc. Development 1998 vol. 125 (18) pp. 3741-51. PMID: 9716539

Zaffran-Maurel C, Hazelett DJ, Lee JD, Benlali A, Treisman JE: The genetic control of early eye development in Drosophila. Dev Biol 1999 vol. 210 pp. 224

Benlali A, Draskovic I, Hazelett DJ, Treisman JE: act up controls actin polymerization to alter cell shape and restrict Hedgehog signaling in the Drosophila eye disc. Cell 2000 vol. 101 (3) pp. 271-81. PMID: 10847682

Janody F, Lee JD, Jahren N, Hazelett DJ, Benlali A, Miura GI, Draskovic I, Treisman JE: A mosaic genetic screen reveals distinct roles for trithorax and polycomb group genes in Drosophila eye development. Genetics 2004 vol. 166 pp. 187-200. PMID: 15020417

Hazelett DJ, Weeks JC: Segment-specific muscle degeneration is triggered directly by a steroid hormone during insect metamorphosis. J Neurobiol 2005 vol. 62 pp.164-77. PMID: 15452849

Hazelett DJ, Lakeland DL, Weiss JB: Affinity density: a novel genomic approach to the identification of transcription factor regulatory targets. Bioinformatics 2009 vol. 25 (13) pp. 1617-24. PMID: 19401399

Morton DB, Clemens-Grisham R, Hazelett DJ, Vermehren-Schmaedick A: Infertility and male mating behavior deficits associated with Pde1c in Drosophila melanogaster. Genetics 2010 vol. 186 (1) pp. 159-65. PMID: 20551439

Pratt EB, Wentzell JS, Maxson JE, Courter L, Hazelett D, Christian JL: The cell giveth and the cell taketh away: an overview of Notch pathwy activation by endocytic trafficking of ligands and receptors. Acta Histochem 2011 vol. 113 (3) pp. 248-55. PMID: 20122714

Hazelett DJ, Chang JC, Lakeland DL, Morton DB: Comparison of parallel high-throughput RNA sequencing between knockout of TDP-43 and its overexpression reveals primarily nonreciprocal and nonoverlapping gene expression changes in the central nervous system of Drosophila. G3 (Bethesda) 2012 vol. 2 (7) pp. 789-802. PMID: 22870402

Hazelett DJCoetzee SG, Coetzee GA: A rare variant, which destroys a FoxA1 site at 8q24, is associated with prostate cancer risk. Cell Cycle 2013 vol. 12 pp. 379-80. PMID: 23255135

Chang JC, Hazelett DJ, Stewart JA, Morton DB: Motor neuron expression of the voltage-gated calcium channel cacophony restores locomotion defects in a Drosophila, TDP-43 loss of function model of ALS. Brain Res 2013 pii: S0006-8993 (13) 01514-X. PMID: 2427519

Hazelett DJ, Rhie SK, Gaddis M, Yan C, Lakeland DL, Coetzee SG; Ellipse/GAME-ON consortium; Practical consortium, Henderson BE, Noushmehr H, Cozen W, Kote-Jarai Z, Eeles RA, Easton DF, Haiman CA, Lu W, Farnham PJ, Coetzee GA: Comprehensive functional annotation of 77 prostate cancer risk loci. PLoS Gen 2014 vol. 10 e1004102. PMID: 24497837

Rhie SK, Hazelett DJ, Coetzee SG, Yan C, Noushmehr H, Coetzee GA: Nucleosome positioning and histone modifications define relationships between regulatory elements and nearby gene expression in breast epithelial cells. BMC Genomics 2014 vol. 15 (1) pp. 331. PMID: 24885402

Cozen W*, Timofeeva MN*, Li D*, Diepstra A*, Hazelett D*, Delahaye-Sourdeix M* and 59 additionla authors: A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus. Nat Commun 2014 vol. 5 pp. 3856. PMID: 24920014

Al Olama AA, Kote-Jarai Z, Berndt SI, Conti D, Schumacher F, Han Y, Benlloch S, Hazelett DJ and 160 additional authors: A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet 2014 vol. 46 pp. 1103-9. PMID: 25217961

Kuchenbaecker K, Ramus S, Tyrer J, Shen H, Lawrenson K, Beesley J, Lee J, Spindler T, Lin Y, Pejovic T, Bean Y, Li Q, Coetzee S, Hazelett D, and 68 additional authors: Identification of six novel, common variant susceptibility loci for invasive epithelial ovarian cancer. Nat Genet 2015 vol. 47 pp. 164-71. PMID: 25581431

Jeong S, Patel N, Edlund C, Hartiala J, Hazelett DJ, Itakura T, Avery RL, Davis JL, Flynn HW, Lalwani G, Puliafito C, Wafapoor H, Hijikata M, Keicho N, Gao X, Argueso P, Allayee H, Coetzee GA, Pletcher MT, Conti DV, Schwartz SG, Eaton AM, Fini ME: Identification of a novel mucin gene HCG22 associated with steroid-induced ocular hypertension. Invest Opthalmol Vis Sci 2015 vol. 56 (4):2737-48. PMID: 25813999

Coetzee SG*, Shen H*, Hazelett DJ*,  and 21 additional authors: Regulatory profiling of ovarian cancer precursor tissues and functional annotation of cancer susceptibility loci Hum Mol Gen 2015 vol. 24 (13):3595-607. PMID: 25804953

Al Olama AA, Dadaev T, Hazelett DJ and 74 additional authors. Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans. Hum Mol Gen 2015 vol. 24 (19):5589-602. PMID: 26025378

Han Y*, Hazelett DJ* and 80 additional authors. Integration of multiethnic fine mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions. Hum Mol Gen 2015 vol. 24 (19):5603-18. PMID: 26823525

Coetzee SG, Coetzee GA, Hazelett DJ. MotifbreakR: an R/Bioconductor package for predicting variant effects at transcription factor binding sites. Bioinformatics 2015 vol. 31 (23):3847-9. PMID: 26272984

Lawrenson K, Iversen ES, Tyrer J, Weber RP, Concannon P, Hazelett DJ, and 152 additional authors. Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer. Carcinogenesis 2015 vol. 36 (11):1341-53. PMID: 26424751

Hazelett DJ, Conti DV, Han Y, Al Oloma AA, Easton D, Eeles RA, Kote-Jarai Z, Haiman CA and Coetzee GA. Reducing GWAS complexity. Cell Cycle 2016 vol. 15 (1):22-24. PMID: 26771711

Han Y, Rand KA, Hazelett DJ and 62 additional authors. Prostate Cancer Susceptibility in Men of African Ancestry at 8q24. J Natl Cancer Inst 2016 108 (7):pii PMID: 26823525

Rand KA, Song C, Dean E, Serie DJ, Curtin K, + 99 additional authors, Hazelett DJ, Cozen W, Haiman CA. A meta-analysis of multiple myeloma risk regions in African and European ancestry populations identifies putatively functional loci. CEBP 2016

Coetzee SG, Brundin P, Hazelett DJ, Coetzee GA. Parkinson’s Disease Risk Functionality. Scientific Reports 2016 6:30509. 

Kar S, Adler E, Tyrer J, Hazelett D and 19 other authors. Enrichment of putativ PAX8 target genes at serous epithelial ovarian cancer susceptibility loci. British Journal of Cancer 2016. 

Amos C, Dennis J, Wang Z, 17 additional authors, Hazelett DJ, and 63 additional authors. The OncoArray Consortium: a Network for Understanding the Genetic Architecture of Common Cancers. CEBP 2016. 

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