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Bradley P. Coe, PhD

Graduate Student Alumni & Research Associate (Currently postdoctoral fellow with Dr. Evan Eichler)

bcoe@bccrc.ca   675 West 10th Avenue, Vancouver, B.C., V5Z 1L3, Canada 

| BCCA | BCCRC | Integrative Oncology | Cancer Genetics | Wan Lam Lab | Brad Coe |


Bradley Coe 


Research Interests

  • Genomics of Small Cell Lung Cancer
  • Technology Development
  • Bioinformatics
  • Sequencing and Microarrays

Lung cancer accounts for the majority of cancer deaths in Canada. 25% of the yearly cases can be attributed to a particular variant called Small Cell Lung Cancer (SCLC). Patients who are diagnosed with SCLC are presented with a very poor prognosis. In fact, only 10% of patients survive past 5 years. This survival statistic has seen little improvement over the past several decades and new targets for therapy and diagnosis of the disease are desperately needed.

Small Cell Lung Cancer has been a challenge to research study for two reasons. First, SCLC samples are difficult to obtain since they are rarely surgically resected. Secondly, the type of cell from which SCLC develops is not known, making it difficult to define normal gene expression (RNA) levels for comparison against that of the tumour. I will overcome the gene expression level problem by focussing on changes found in the DNA rather than the RNA found in SCLC cells. Most alterations in RNA levels can be traced to the gain or loss of the specific DNA segments which contain the instructions for producing the functional gene product. Analysis of DNA has the significant advantage that the source cell is not needed for establishing a baseline as any human tissue can be used. Sample acquisition has been arranged through collaboration with national and international groups that are experts in SCLC pathology.

In order to identify the genes which are specific to the aggressive nature of SCLC I will compare the DNA profiles I generate for SCLC with profiles I will generate for similar types of lung cancer which are less aggressive. This is made possible by a new genome comparison technology developed in our laboratory. I have developed bioinformatics tools to distinguish the alterations present in the less aggressive lung cancers. The outcome of this project will be a list of genes which may contribute to aggressiveness.

This list of genes will both serve to enhance our knowledge of the biology of SCLC as well as identify potential targets for future therapeutics. Additionally these alterations will immediately be utilizable as diagnostic markers to assist in the classification and diagnosis of this disease.

In addition to studying SCLC, my work also focuses on the continued development of array CGH and analysis tools for genomic and transcriptomic data to better understand the genomic status of tumours and normal samples. Recently I have begun to apply sequence based methodologies (SAGE and "Next-Gen Sequencing") to understanding the complex regulation of gene expression beyond what can be determined by microarray analysis, by incorporating the analysis of splice variants (novel and know), allele specific expression, mutations, and expression of novel sequences.  


Publications

  1. Cooper GM*, Coe BP*, Girirajan S*, Rosenfeld JA, Vu TH, Baker C, Williams C, Stalker H, Hamid R, Hannig V, Abdel-Hamid H, Bader P, McCracken E, Niyazov D, Leppig K, Thiese H, Hummel M, Alexander N, Gorski J, Kussmann J, Shashi V, Johnson K, Rehder C, Ballif BC, Shaffer LG, Eichler EE (2011) A copy number variation morbidity map of developmental delay. Nature Genetics 43(9):838-46. * equal contribution.
  2. Alkan C, Coe BP, Eichler EE (2011) Genome structural variation discovery and genotyping. Nature Reviews Genetics 12(5):363-76.
  3. Tucker T, Montpetit A, Chai D, Chan S, Chénier S, Coe BP, Delaney A, Eydoux P, Lam WL, Langlois S, Lemyre E, Marra M, Qian H, Rouleau GA, Vincent D, Michaud JL, Friedman JM (2011) Comparison of genome-wide array genomic hybridization platforms for the detection of copy number variants in idiopathic mental retardation. BMC Medical Genomics 4:25, 1-10.
  4. Chari R, Lonergan KM, Pikor LA, Coe BP, Zhu CQ, Chan THW, MacAulay C, Tsao MS, Lam S, Ng RT, Lam WL (2010) A sequence-based approach to identify reference genes for gene expression analysis.  BMC Medical Genomics 3:32, 1-11. 
  5. Lockwood WW, Chari R, Coe BP, Thu KL, Garnis C, Malloff CA, Campbell JM, Williams AC, Hwang D, Chang QZ, Buys TPH, Yee J, English J, MacAulay C, Tsao MS, Gazdar AF, Minna JD, Lam S, Lam WL (2010) Integrative genomic analyses identify BRF2 as a novel lineage specific oncogene in lung squamous cell carcinoma. PLoS Medicine 7(7): e1000315, 1-14.
  6. Coe BP, Chari R, MacAulay C, Lam WL (2010) FACADE: A fast and sensitive algorithm for the segmentation and calling of high resolution array CGH data. Nucleic Acids Research. Epub ahead of print 2010 Jun 15.
  7. Chari R, Coe BP, Vucic EA, Lockwood WW, Lam WL (2010) An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer. BMC Systems Biology 4: 67, 1-14.
  8. Chari R, Thu KL, Wilson IM, Lockwood WW, Lonergan KM, Coe BP, Malloff CA, Gazdar AF, Lam S, Garnis C, MacAulay CE, Alvarez CE, Lam WL (2010) Integrating the multiple dimensions of genomic and epigenomic lanscapes of cancer. Cancer and Metastasis Reviews 29: 73-93.
  9. Lonergan, KM, Chari R, Coe BP, Wilson IM, Tsao MS, Ng RT, MacAulay C, Lam S, Lam WL (2010) Transcriptome profiles of carcinoma-in-situ and invasive non-small cell lung cancer as revealed by SAGE. PLoS ONE 5: e9162, 1-22.
  10. Vucic EA, Thu KL, Williams AC, Lam WL, Coe BP (2010) Copy number variations in the human genome and strategies for analysis. Methods in Molecular Biology 628:103-17.
  11. Thu KL, Lam WL, Coe BP (2009) The emerging role of copy number variation in cancer. Cell Science 6: 98, 1-23.
  12. Coe BP, Lockwood WW, Chari R, Lam WL (2009) Comparative Genomic Hybridization on BAC Arrays. Methods in Molecular Biology 556: 7-19.
  13. Chari R, Coe BP, Wedseltoft C, Benetti M, Wilson IM., Vucic EA., MacAulay C, Ng RT, Lam WL (2008) SIGMA2: A system for the integrative genomic multi-dimensional analysis of cancer genomes, epigenomes, and transcriptomes. BMC Bioinformatics 9:422, 1-12.
  14. Campbell JM*, Lockwood WW*, Buys THP, Chari R, Coe BP, Lam S, Lam WL (2008) Integrative genomic and gene expression analysis of chromosome 7 identified novel oncogene loci in non-small cell lung cancer. Genome 51: 1032-1039.
  15. Coe BP, Chari R, Lockwood WW, Lam WL (2008) Evolving strategies for global gene expression analysis of cancer. Journal of Cellular Physiology 217: 590-597,
  16. Aviel-Ronen S, Coe BP, Lau SK, Zhu CQ, Strumpf D, Santos GC, Shepard FA, Jurisica I, Lam WL, Tsao MS. (2008) The genetic signature of invasion and poor prognosis that defines lung adenocarcinoma with bronchioloalveolar features.Proceedings of the National Academy of Sciences. 105: 10155-10160
  17. Chi B, DeLeeuw RJ, Coe BP, Ng RT, MacAulay C, Lam WL (2008) MD-SeeGH: a platform for integrative analysis of multidimensional data. BMC Bioinformatics 20(9): 243
  18. Coe BP, Ylstra, B, Carvalho B, Meijer GA, MacAulay C, Lam WL, (2008) Comment re: a comparison of DNA copy number profiling platforms. Cancer Research 68(10): 4010
  19. Wang J-C, Coe BP, Lomax B, MacLeod P, Parslow M, Schein JE, Lam WL, Eydoux P (2008) Inverted duplication with terminal deletion of 5p and no cat-like cry. American Journal of Medical Genetics 146A(9): 1173-9
  20. Lockwood WW, Chari R, Coe BP, Girard L, MacAulay C, Lam S, Gazdar AF, Minna JD, Lam WL (2008) DNA amplification is a ubiquitous mechanism of oncogene activation in lung and other cancers. Oncogene 27: 4615-4624
  21. Buys TPH, Wilson IM, Coe BP, Lee EHL, Kennett JY, Lockwood WW, Tsui IFL, Shadeo A, Chari R, Garnis C, Lam WL. (2008) ″Detailed comparisons of cancer genomes″ in comparative genomics: fundamental and applied perspectives (Brown JR, ed.), CRC Press ⁄ Taylor and Francis, LLC. Boca Raton, FLA, pp. 245-59.
  22. Buys TP, Wilson IM, Coe BP, Lockwood WW, Davies JJ, Chari R, DeLeeuw RJ, Shadeo A, MacAulay C, and Lam WL. (2008) ″Key features of BAC array production and usage″ in DNA microarrays (Methods Express Series) (Schena M, ed), Scion Publishing, Ltd., Bloxham, pp 85-115. 
  23. Coe BP, Ylstra B, Carvalho B, Meijer GA, MacAulay C, Lam WL (2007) Resolving the resolution of array CGH. Genomics. 89(5): 647-53
  24. Coe BP*, Lockwood WW*, Girard L, Chari R, MacAulay C, Lam S, Gazdar AF, Minna JD, Lam WL (2006) Differential regulation of cell cycle pathways in small cell and non-small cell lung cancer. British Journal of Cancer. 94(12): 1927-1935 * These Authors Contributed Equally
  25. Coe BP, Lee EH, Chi B, Girard L, Minna JD, Gazdar AF, Lam S, MacAulay C, Lam WL (2006) Gain of a region on 7p22.3, containing MAD1L1, is the most frequent event in small-cell lung cancer cell lines. Genes Chromosomes Cancer. 45(1): 11-19
  26. Chari R, Lockwood WW, Coe BP, Chu A, Macey D, Thomson A, Davies JJ, MacAulay C, Lam WL. (2006) SIGMA: A system for the integrative genomic microarray analysis of cancer genomes. BMC Genomics. 27(7): 324
  27. Lockwood WW, Coe BP, William AC, MacAulay C, Lam WL. (2006) Whole genome tiling path array CGH analysis of segmental copy number alterations in cervical cancer cell lines. International Journal Cancer. 120(2): 436-443
  28. Aviel-Ronen S, Zhu CQ, Coe BP, Liu N, Watson SK, Lam WL, Tsao MS (2006) Large fragment Bst DNA polymerase for whole genome amplification of DNA from formalin-fixed paraffin-embedded tissues. BMC Genomics 12(7): 312
  29. Khojasteh M, Coe BP, Shah S, Ward RK, Lam WL, MacAulay C (2006) A novel algorithm for the analysis of array CGH data.IEEE Conference on Acoustics, Speech, and Signal Processing (II):1020-1032.
  30. Coe BP, Henderson LJ, Garnis C, Tsao-MS, Lam S, Minna J, MacAulay C, Lam WL (2005) High resolution chromosome 5p array CGH analysis of small cell lung carcinoma cell lines. Genes Chromosomes and Cancer. 542(3): 308-313.
  31. Henderson LJ, Coe BP, Gazdar AF, Minna JD, Lam S, MacAulay C, Lam WL (2005) Genomic and gene expression profiling of minute alterations of chromosome arm 1p in small-cell lung carcinoma cells. British Journal of Cancer. 92(8): 1553-1560
  32. Garnis C*, Coe BP*, Lam S, MacAulay C, Lam WL (2005) Improved array resolution reduces tissue microdissection requirement for array CGH. Genomics. 85(6): 790-793 * These Authors Contributed Equally
  33. Chi B, deLeeuw R, Coe BP, MacAulay C, Lam WL (2003) SeeGH A software tool for visualization of whole genome array comparitive genomic hybridization data. BMC Bioinformatics 5(1): 13,1-6
  34. Ishkanian AS, Malloff C, Watson S, deLeeuw R, Chi B, Coe BP, Snijders A, Albertson DG, Pinkel D, Marra M, Ling V, MacAulay C, Lam WL (2003) A Tiling Resolution DNA microarray with complete coverage of the human genome. Nature Genetics 36(3): 299-303
  35. Garnis C, Coe BP, Zhang L, Rosin MP, Lam WL (2003) Overexpression of LRP12, a gene contained within an 8q22 amplicon identified by high-resolution array CGH analysis of oral squamous cell carcinomas. Oncogene 23(14): 2582-2586
  36. Garnis C, Coe BP, Ishkanian A, Zhang L, Rosin MP, Lam WL (2003) Novel regions of amplification on 8q distinct from the MYC locus and frequently altered in oral dysplasia and cancer. Genes Chromosomes and Cancer 39(1): 93-98

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| BCCA | BCCRC | Integrative Oncology | Cancer Genetics | Wan Lam Lab | Brad Coe |