Research Interest: I am interested in using genetic, genomic, and proteomic data to understand and model the biology of cancer and to develop methods to effectively deploy therapeutic agents in the age of molecularly guided medicine. Members of my lab use a combination of conventional molecular biology, high throughput genomic and proteomic assays, and bioinformatic analyses in their work.
Cancer Genomics: My group participates in numerous collaborations to understand the effects of genome aberrations in cancer. These efforts include development of new methodologies for identifying changes in the cancer genome, systematic integration of multiple genomic data types (copy number, expression, and mutation) to better understand the process by which cancer develops, and the application of cell line systems as models for the genetic heterogeneity within cancers. Two major recent thrusts are the systematic characterization of cancer genomes as part of The Cancer Genome Atlas (TCGA Network, Nature, 2011) and the development and application of methods to reconstruct tumor evolution (Durinck et al. Cancer Discover, 2011). We aim to push these analyses forward in continued analysis of ovarian cancer genomes as well as kidney and breast cancer genomes.
Modeling of Signaling Systems: In collaboration with Sach Mukherjee (NKI) the group is developing methods for computationally modeling the signaling that occurs in cancer cells. The idea behind the current work is to create Bayesian estimates of signaling systems from both dynamic and static signaling processes.
Immune System Therapies: It has been observed that the survival of breast cancer patients is related to the presence of immune system signatures and T cell infiltrates in a patient’s tumors. The hypothesis is that stimulating the immune system can be an effective mode of therapy. In collaboration with Peter Lee at Stanford and Jill Kapler at Nationwide Jewish we aim to develop approaches to stimulate the natural immune response in breast cancer patients.
We are funded in these efforts by the NCI Centers for Cancer Systems Biology (icbp.nci.nih.gov/), The Cancer Genome Atlas (cancergenome.nih.gov), a DoD Multi-team award, the Bay Area Breast SPORE, collaborations with private industry, and the Knight Cancer Center at OHSU.
P.T. Spellman, G. Sherlock, M. Q. Zhang, V. R. Iyer, K. Anders, M. B. Eisen, P. O. Brown, D. Botstein and B. Futcher. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Molecular Biology of the Cell 9: 3273-97, 1998.
M. B. Eisen, P.T. Spellman, P. O. Brown and D. Botstein. Cluster analysis and display of genome-wide expression patterns. Proceedings of the National Academy of Sciences, U.S.A. 95: 14863-8, 1998.
D. T. Ross, U. Scherf, M. B. Eisen, C. M. Perou, C. Rees, P. Spellman, V. Iyer, S. S. Jeffrey, M. Van de Rijn, M. Waltham, A. Pergamenschikov, J. C. Lee, D. Lashkari, D. Shalon, T. G. Myers, J. N. Weinstein, D. Botstein and P. O. Brown. Systematic variation in gene expression patterns in human cancer cell lines. Nature Genetics 24: 227-35, 2000.
R.M. Neve, K. Chin, J. Fridlyand, J. Yeh, F.L. Baehner, T. Fevr, L. Clark, N. Bayani, J.P. Coppe JP, F. Tong, T. Speed, P.T. Spellman, S. DeVries, A. Lapuk, N.J. Wang, W.L. Kuo, J.L. Stilwell, D. Pinkel, D.G. Albertson, F.M. Waldman, F. McCormick, R.B. Dickson, M.D. Johnson, M. Lippman, S. Ethier, A. Gazdar, J.W. Gray. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 6:515-27. 2006
Y. Wang, M. Moorhead, G. Karlin-Neumann, N. Wang, J. Ireland, S. Lin, C. Chen, L.M. Heiser, K. Chin, L. Esserman, J.W. Gray, P.T. Spellman. M. Faham. Performance of Molecular Inversion Probes (MIP) in Allele Copy Number Determination. Genome Biology. 8:R246. 2007
The Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008
S. Durinck, J. Bullard, P.T. Spellman, S. Dudoit. GenomeGraphs: Integrated genomic visualization with R. BMC Bioinformatics. 2009
H. Bengtsson, A. Ray, P. Spellman, T.P. Speed. A single-sample method for normalizing and combining full-resolution copy numbers from multiple platforms, labs and analysis methods. Bioinformatics. 2009
L.M. Heiser, N.J. Wang, C.L. Talcott, K.R. Laderoute, M. Knapp, Y. Guan, Z. Hu, S. Ziyad, B.L. Weber, S Laquerre, J.R. Jackson, R.F. Wooster, W.L. Kuo, J.W. Gray, P.T. Spellman. Genome Biology. 2009
S. Durinck, P.T. Spellman, W. Huber. Mapping Identifiers for the Integration of Genomic Datasets with the R/Bioconductor package biomaRt. Nature Protocols. 2009
International Cancer Genome Consortium. International network of cancer genome projects. Nature. 2010.
E.A. Collisson, A. Sadanandam, P. Olson, W.J. Gibb, M. Truitt, S. Gu, J. Cooc, J. Weinkle, G.E. Kim, L. Jakkula, H.S. Feiler, A.H. Koh, A.B. Olshen, K.L. Danenberg, M.A. Tempero, P.T. Spellman, D. Hanahan, and J.W. Gray. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat. Med. 2011
TCGA Network, P.T. Spellman corresponding author. Integrative Genomic Analyses of Ovarian Carcinoma. Nature. In press.
S. Durinck, C. Ho, N.J. Wang, W. Liao, L.R. Jakkula, E.A. Collisson, J. Pons, S.W. Chan, E.T. Lam, C. Chu, K. Park, S.W. Hong, J.S. Hur, N. Huh, I.M. Neuhaus, S.S. Yu, R.T. Grekin, T.M. Mauro, J.E. Cleaver, P.Y. Kwok, P.E. LeBoit, G. Getz, K. Cibulskis, J.C. Aster, H. Huang, E. Purdom, J. Li, L. Bolund, S. Arron, J.W. Gray, P.T. Spellman*, R.J. Cho* (*corresponding authors). Temporal Dissection of Tumorigenesis in Primary Cancers. Cancer Discovery. In press.