PRECLINICAL & TRANSLATIONAL RESEARCH
Cancer Computational Biology group
JOSE A. SEOANE
Principal Investigator
Biosketch
The Cancer Computational Biology group leverages epi(genetic) cancer datasets to discover the molecular mechanism involved in cancer initiation, progression, drug resistance and metastasis in order to improve patient outlooks.
Through the group’s work, we have shown how the genes that modify the chromatin structure are associated with chemotherapy resistance in breast cancer (Nature Medicine, 2019). Our goal is to understand how these epigenetic modifications affect drug resistance and how epigenetic drugs can be used to target tumor suppressor genes.
We are also interested in how the machine learning-based integration of multi-omic datasets can aid in the discovery of new cancer subgroups and biomarkers as well as the prediction of outcome and drug response.
We have participated in multiple international consortiums, including The Cancer Genome Atlas, the Human Tumor Atlas Network, Cancer Target Discovery and Development and, most recently, AURORA (metastatic breast cancer multi-omic cohort).
RESEARCH LINES
- Role of chromatin regulatory elements in drug response and metastasis
- New epigenetic synthetic lethality-based therapeutic options
- Patient stratification using multi-omic analysis
- New epigenetic biomarkers of drug response
STRATEGIC GOALS
- Understand the role of chromatin regulatory elements in drug response and metastasis
- Discover new epigenetic biomarkers of drug response
- Improve therapeutic options by combining epigenetic drugs with other agents
PROJECTS
Targeting synthetic lethality in Chromatin Regulatory Genes for gastrointestinal cancer treatment. Ref PID2020-115097RA-I00. Agencia Estatal de Investigación. 9/2021-8/2025. PI: Jose A. Seoane
Ramon y Cajal Grant. Agencia Estatal de Investigación. 2021-2025.
TEAM
- Principal Investigator
- Jose A. Seoane
- Postdoctoral fellows
- Silvana Maas
- Graduate students
- Arnau Llinas
- Mª José Fariñas
- Master’s degree student
- Odei Blanco
PUBLICATIONS
- DCIS genomic signatures define biology and correlate with clinical outcome: a Human Tumor Atlas Network (HTAN) analysis of TBCRC 038 and RAHBT cohorts
Siri H. Strand, Belén Rivero-Gutiérrez, Kathleen E. Houlahan, Jose A. Seoane, Lorraine King, …,Christina Curtis, Rob Tibshirani, Robert Michael Angelo, Allison Hall, Kouros Owzar, Kornelia Polyak, Carlo Maley, Jeffrey R. Marks, Graham A. Colditz, E. Shelley Hwang, Robert B. West
bioRxiv, June 2021
10.1101/2021.06.16.448585 - CRISPR screens in cancer spheroids identify 3D growth-specific vulnerabilities
Kyuho Han, Sarah E. Pierce, Amy Li, Kaitlyn Spees, Grace R. Anderson, Jose A. Seoane, Yuan-Hung Lo, Michael Dubreuil, Micah Olivas, Roarke A. Kamber, Michael Wainberg, Kaja Kostyrko, Marcus R. Kelly, Maryam Yousefi, Scott W. Simpkins, David Yao, Keonil Lee, Calvin J. Kuo, Peter K. Jackson, Alejandro Sweet-Cordero, Anshul Kundaje, Andrew J. Gentles, Christina Curtis, Monte M. Winslow, Michael C. Bassik
Nature, 580(7801):136-141, April 2020
URL: www.nature.com/articles/s41586-020-2099-x - Convergent mutations in tissue-specific regulatory regions reveal novel cancer drivers
Nasa Sinnott-Armstrong, Jose A. Seoane, Jonathan K. Pritchard, Christina Curtis, Michael P. Snyder
bioRxiv, November 2020
URL:https://www.biorxiv.org/content/10.1101/2020.08.21.239954v1.abstract - Chromatin regulators mediate anthracycline sensitivity in breast cancer
Jose A. Seoane, Jacob G. Kirkland, Jennifer L. Caswell-Jin, Gerald R. Crabtree, Christina Curtis
Nature Medicine, 25(11):1721-1727, November 2019
URL: www.nature.com/articles/s41591-019-0638-5 - Dynamics of breast-cancer relapse reveal late-recurring ER-positive genomic subgroups
Oscar M. Rueda, Stephen-John Sammut, Jose A. Seoane, Suet-Feung Chin, Jennifer L. Caswell-Jin, Maurizio Callari, Rajbir Batra, Bernard Pereira, Alejandra Bruna, H. Raza Ali, Elena Provenzano, Bin Liu, Michelle Parisien, Cheryl Gillett, Steven McKinney, Andrew R. Green, Leigh Murphy, Arnie Purushotham, Ian O. Ellis, Paul D. Pharoah, Cristina Rueda, Samuel Aparicio, Carlos Caldas, Christina Curtis
Nature, 567(7748):399-404, March 2019
URL: www.nature.com/articles/s41586-019-1007-8 - Assessment of ERBB2/HER2 status in HER2-equivocal breast cancers by FISH and 2013/2014 ASCO-CAP guidelines
Michael F. Press, Jose A. Seoane, Christina Curtis, Emmanuel Quinaux, Roberta Guzman, Guido Sauter, Wolfgang Eiermann, John R. Mackey, Nicholas Robert, Tadeusz Pienkowski, John Crown, Miguel Martin, Vicente Valero, Valerie Bee, Yanling Ma, Ivonne Villalobos, Dennis J. Slamon
JAMA Oncology, 5(3):366-375, March 2019
URL:jamanetwork.com/journals/jamaoncology/article-abstract/2718266 - The chromatin accessibility landscape of primary human cancers
Science, 362(6413), October 2018
URL: https://science.sciencemag.org/content/362/6413/eaav1898.abstract - Canonical correlation analysis for gene-based pleiotropy discovery
Jose A. Seoane, Colin Campbell, Ian N. M. Day, Juan P. Casas, Tom R. Gaunt
PLoS Computational Biology, 10(10), October 2014
URL: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003876 - A pathway-based data integration framework for prediction of disease progression
Jose A. Seoane, Ian N. M. Day, Tom R. Gaunt, Colin Campbell
Bioinformatics, 30(6):838-845, Mar. 2014
URL: https://academic.oup.com/bioinformatics/article-abstract/30/6/838/285849