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Raúl Rabadán

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Raúl Rabadán
Born1974 (age 50–51)
Alma materAutonomous University of Madrid (Ph.D. 2001)
Scientific career
FieldsTheoretical physics
Computational biology
Genomics
Mathematical biology
InstitutionsColumbia University
Institute for Advanced Study
CERN
Websiterabadanlab.org

Raúl Rabadán (born 1974) is a Spanish-American theoretical physicist and computational biologist. He is currently the Gerald and Janet Carrus Professor in the Department of Systems Biology, Biomedical Informatics and Surgery at Columbia University. He is the director of the Program for Mathematical Genomics at Columbia University and previously the director of the Center for Topology of Cancer Evolution and Heterogeneity (2015-2021). He is also the co-leader of the Cancer Genetics and Epigenetics Program at the Herbert Irving Comprehensive Cancer Center at Columbia University. At Columbia, he leads a highly interdisciplinary team of researchers from the fields of mathematics, physics, computer science, engineering, and medicine, with the common goal of solving pressing biomedical problems through quantitative computational models. Rabadan's current interest focuses on uncovering patterns of evolution in biological systems—in particular, viruses and cancer.

Career

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Rabadan is an expert on mathematical approaches to biological systems, genomics of cancer and infectious diseases. He received his PhD in string theory phenomenology, specifically the physics of string compactifications and intersecting D-brane configurations in the Universidad Autonoma de Madrid, Spain. From 2001 to 2003, Rabadan was a fellow at the Theoretical Physics Division at CERN, the European Organization for Nuclear Research, in Geneva, Switzerland. In 2003 he joined the Physics Group of the School of Natural Sciences at the Institute for Advanced Study, Princeton, NJ. He studied the information paradox of black holes in the context of the Anti-de Sitter/Conformal Field Theory duality, and has proposed several experiments to search for axions. Since 2005 he has focused his research program on theoretical and computational problems in biology. In 2006 he joined The Simon's Center for Systems Biology at The Institute for Advanced Study, Princeton, NJ.

Since 2008 Rabadan has been a professor at Columbia University, in New York. He has applied quantitative approaches to modeling and understanding the dynamics of biological systems through the lens of genomics. He has focused his research on the evolution of two of such biological systems: cancer and infectious diseases. In particular, he has been working on the identification of driver mechanisms of evolutionary processes, characterization of key process dynamics to elucidate interactions. Rabadan is interested in understanding the evolution of infectious agents through the analysis of their genome, in particular RNA viruses like influenza and coronaviruses. His work in this area includes elucidating the origin of the influenza A virus subtype H1N1.[1][2]

Since 2010 most of Rabadan's work has focused on cancer genomics mostly on three different areas; Genomics of hematological malignancies, brain tumors, and uncovering the role of non-coding RNAs and splicing variants in cancer. His work on hematological malignancies has led to the identification of driver alterations in hairy cell leukemia,[3] diffuse large B-cell lymphoma,[4][5] T-cell acute lymphoblastic leukemia,[6][7] chronic lymphocytic leukemia,[8][9][10][11] splenic marginal zone lymphoma[12] among others. He has been working on identifying driver alterations in glioblastomas[13][14], longitudinal studies of brain tumor evolution under standard therapy[15] and immunotherapies[16], uncovering the role of clonal heterogeneity in brain tumors[17], mapping the role of pharmacogenomics in precision oncology therapies[18]. He has also been involved in studying the role of non-coding RNA and splicing mutations in cancer [19][20][21][22].

He has been leading an active program to bring tools from computer science, physics and mathematics into the study of biological systems. He has been working on the application of topological data analysis to large scale genomic data and transcriptomic single cell data[23][24][25][26][27] . He has recently developed foundational models to understand cell type specific transcriptional programs in human cells[28].

Rabadan's scientific work has led to more than 200 peer-reviewed scientific publications, including in high impact factor journals (New England Journal of Medicine, Nature, Science, Nature Genetics, Nature Medicine, Cell, among others). Several of his results have been featured by the international press, including CNN, the Washington Post, the New York Times, the Wall Street Journal, the Associated Press, Reuters International, and The Economist.

Books

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In 2020 Rabadan together with Andrew Blumberg, a topologist at the University of Texas, published a book Topological Data Analysis for Genomics and Evolution in Cambridge University Press. The books explores biology in the age of Big Data. This book introduces the central ideas and techniques of topological data analysis and its specific applications to biology, including the evolution of viruses, bacteria and humans, genomics of cancer, and single cell characterization of developmental processes.

In 2020 Rabadan published Understanding Coronavirus in Cambridge University Press. The book provides a concise and accessible introduction provides answers to the most common questions surrounding coronavirus for a general audience, including an introduction about the origin and evolution of this virus, the relation to SARS and other respiratory viruses, among other.

References

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  1. ^ Trifonov, V., Khiabanian, H., Greenbaum, B. & Rabadan, R. The origin of the recent swine influenza A(H1N1) virus infecting humans. Euro Surveill 14 (2009).
  2. ^ Trifonov, V.; Khiabanian, H.; Rabadan, R. (2009). "Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus". N Engl J Med. 361 (2): 115–119. doi:10.1056/NEJMp0904572. PMID 19474418.
  3. ^ Tiacci, E.; et al. (2011). "BRAF mutations in hairy-cell leukemia". N Engl J Med. 364 (24): 2305–2315. doi:10.1056/NEJMoa1014209. PMC 3689585. PMID 21663470.
  4. ^ Pasqualucci, L.; et al. (2011). "Inactivating mutations of acetyltransferase genes in B-cell lymphoma". Nature. 471 (7337): 189–195. Bibcode:2011Natur.471..189P. doi:10.1038/nature09730. PMC 3271441. PMID 21390126.
  5. ^ Pasqualucci, L.; et al. (2011). "Analysis of the coding genome of diffuse large B-cell lymphoma". Nat Genet. 43 (9): 830–837. doi:10.1038/ng.892. PMC 3297422. PMID 21804550.
  6. ^ Van Vlierberghe, P.; et al. (2010). "PHF6 mutations in T-cell acute lymphoblastic leukemia". Nat Genet. 42 (4): 338–342. doi:10.1038/ng.542. PMC 2847364. PMID 20228800.
  7. ^ Tzoneva, G.; et al. (2013). "Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL". Nat Med. 19 (3): 368–371. doi:10.1038/nm.3078. PMC 3594483. PMID 23377281.
  8. ^ Rossi, D. et al. Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood 119, 521-529, doi:10.1182/blood-2011-09-379966 (2012).
  9. ^ Rossi, D.; et al. (2012). "Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia". Blood. 121 (8): 1403–1412. doi:10.1182/blood-2012-09-458265. PMC 3578955. PMID 23243274.
  10. ^ Rossi, D.; et al. (2011). "Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness". Blood. 118 (26): 6904–6908. doi:10.1182/blood-2011-08-373159. PMC 3245210. PMID 22039264.
  11. ^ Jiguang Wang, Hossein Khiabanian, Davide Rossi, Giulia Fabbri, Valter Gattei, Francesco Forconi, Luca Laurenti, Roberto Marasca, Giovanni Del Poeta, Robin Foà, Laura Pasqualucci, Gianluca Gaidano, Raul Rabadan. Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia. eLife 2014 Dec 11; doi:10.7554/eLife.02869 PMID 25496728.
  12. ^ Rossi, D.; et al. (2012). "The coding genome of splenic marginal zone lymphoma:activation of NOTCH2 and other pathways regulating marginal zone development". J Exp Med. 209 (9): 1537–1551. doi:10.1084/jem.20120904. PMC 3428941. PMID 22891273.
  13. ^ Singh, D. et al. Transforming Fusions of FGFR and TACC Genes in Human Glioblastoma. Science, doi:10.1126/science.1220834.
  14. ^ Veronique Frattini, Vladimir Trifonov, Joseph Minhow Chan, Angelica Castano, Marie Lia, Francesco Abate, Stephen T. Keir, Alan X. Ji, Pietro Zoppoli, Francesco Niola, Carla Danussi, Igor Dolgalev, Paola Porrati, Serena Pellegatta, Adriana Heguy, Gaurav Gupta, David J. Pisapia, Peter Canoll, Jeffrey N. Bruce, Roger E. McLendon, Hai Yan, Ken Aldape, Gaetano Finocchiaro, Tom Mikkelsen, Gilbert G. Privé, Darell D. Bigner, Anna Lasorella, Raul Rabadan, Antonio Iavarone. The integrated landscape of driver genomic alterations in glioblastoma. Nature Genetics 2013 Aug 5. doi:10.1038/ng.2734. PMC 3677224.
  15. ^ Jiguang Wang, Emanuela Cazzato, Erik Ladewig, Veronique Frattini, Daniel S. Rosenbloom, Sakellarios Zairis, Francesco Abate, Zhaoqi Liu, Oliver Elliott, Yong-Jae Shin, Jin-Ku Lee, In-Hee Lee, Woong-Yang Park, Marica Eoli, Andrew Blumberg, Anna Lasorella, Do-Hyun Nam, Gaetano Finocchiaro, Antonio Iavarone, Raul Rabadan, Clonal Evolution of Glioblastoma under Therapy, Nature Genetics 2016 June 6. doi:10.1038/ng.3590.
  16. ^ Zhao J, Chen AX, Gartrell RD, Silverman AM, Aparicio L, Chu T, Bordbar D, Shan D, Samanamud J, Mahajan A, Filip I, Orenbuch R, Goetz M, Yamaguchi JT, Cloney M, Horbinski C, Lukas RV, Raizer J, Rae AI, Yuan J, Canoll P, Bruce JN, Saenger YM, Sims P, Iwamoto FM, Sonabend AM, Rabadan R. Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma. doi:10.1038/s41591-019-0349-y.
  17. ^ Lee, Jin-Ku; Wang, Jiguang; Sa, Jason K; Ladewig, Erik; Lee, Hae-Ock; Lee, In-Hee; Kang, Hyun Ju; Rosenbloom, Daniel S; Camara, Pablo G; Liu, Zhaoqi; van Nieuwenhuizen, Patrick; Jung, Sang Won; Choi, Seung Won; Kim, Junhyung; Chen, Andrew (April 2017). "Spatiotemporal genomic architecture informs precision oncology in glioblastoma". Nature Genetics. 49 (4): 594–599. doi:10.1038/ng.3806. ISSN 1061-4036. PMC 5627771. PMID 28263318.
  18. ^ Lee, Jin-Ku; Liu, Zhaoqi; Sa, Jason K.; Shin, Sang; Wang, Jiguang; Bordyuh, Mykola; Cho, Hee Jin; Elliott, Oliver; Chu, Timothy; Choi, Seung Won; Rosenbloom, Daniel I. S.; Lee, In-Hee; Shin, Yong Jae; Kang, Hyun Ju; Kim, Donggeon (October 2018). "Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy". Nature Genetics. 50 (10): 1399–1411. doi:10.1038/s41588-018-0209-6. ISSN 1061-4036. PMC 8514738. PMID 30262818.
  19. ^ E. Pefanis, J. Wang, G. Rothschild, J. Lim, J. Chao, R. Rabadan, AN. Economides, U. Basu. Antisense non-coding RNA transcription targets AID to divergently transcribed genes in the B cell genome. Nature 514, 389–393 ( co-corresponding authors).
  20. ^ Evangelos Pefanis, Jiguang Wang, Gerson Rothschild, Junghyun Lim, David Kazadi, Jianbo Sun, Alexander Federation, Jaime Chao, Oliver Elliott, Zhi-Ping Liu, Aris N. Economides, James E. Bradner, Raul Rabadan, Uttiya Basu. RNA Exosome-Regulated Long Non-Coding RNA Transcription Controls Super-Enhancer Activity. Cell 2015 May; doi:10.1016/j.cell.2015.04.034
  21. ^ Arnes, Luis; Liu, Zhaoqi; Wang, Jiguang; Maurer, Carlo; Sagalovskiy, Irina; Sanchez-Martin, Marta; Bommakanti, Nikhil; Garofalo, Diana C; Balderes, Dina A; Sussel, Lori; Olive, Kenneth P; Rabadan, Raul (March 2019). "Comprehensive characterisation of compartment-specific long non-coding RNAs associated with pancreatic ductal adenocarcinoma". Gut. 68 (3): 499–511. doi:10.1136/gutjnl-2017-314353. ISSN 0017-5749. PMC 6086768. PMID 29440233.
  22. ^ Liu, Zhaoqi; Yoshimi, Akihide; Wang, Jiguang; Cho, Hana; Chun-Wei Lee, Stanley; Ki, Michelle; Bitner, Lillian; Chu, Timothy; Shah, Harshal; Liu, Bo; Mato, Anthony R.; Ruvolo, Peter; Fabbri, Giulia; Pasqualucci, Laura; Abdel-Wahab, Omar (1 June 2020). "Mutations in the RNA Splicing Factor SF3B1 Promote Tumorigenesis through MYC Stabilization". Cancer Discovery. 10 (6): 806–821. doi:10.1158/2159-8290.CD-19-1330. ISSN 2159-8274. PMC 8188517. PMID 32188705.
  23. ^ Chan, J. M.; Carlsson, G.; Rabadan, R. (2013). "Topology of viral evolution". Proc Natl Acad Sci U S A. 110 (46): 18566–18571. Bibcode:2013PNAS..11018566C. doi:10.1073/pnas.1313480110. PMC 3831954. PMID 24170857.
  24. ^ K. Emmett, R. R. Characterizing Scales of Genetic Recombination and Antibiotic Resistance in Pathogenic Bacteria Using Topological Data Analysis. Lecture Notes in Computer Science (LNCS) (2014).
  25. ^ Camara, Pablo G.; Rosenbloom, Daniel I. S.; Emmett, Kevin J.; Levine, Arnold J.; Rabadan, Raul (2016). "Fine-scale resolution of human recombination using topological data analysis". Cell Systems. 3 (1): 83–94. doi:10.1016/j.cels.2016.05.008. PMC 4965322. PMID 27345159.
  26. ^ S. Zairis, A. Blumberg, H. Khiabanian, R. Rabadan. Moduli spaces of phylogenetic trees describing tumor evolutionary patterns. Lecture Notes in Computer Science (LNCS) 2014. Volume 8609, pp 528-539. 2.
  27. ^ Rizvi, Abbas H.; Camara, Pablo G.; Kandror, Elena K.; Roberts, Thomas J.; Schieren, Ira; Maniatis, Tom; Rabadan, Raul (June 2017). "Single-cell topological RNA-seq analysis reveals insights into cellular differentiation and development". Nature Biotechnology. 35 (6): 551–560. doi:10.1038/nbt.3854. ISSN 1546-1696. PMC 5569300. PMID 28459448.
  28. ^ Fu, Xi; Mo, Shentong; Buendia, Alejandro; Laurent, Anouchka P.; Shao, Anqi; Alvarez-Torres, Maria del Mar; Yu, Tianji; Tan, Jimin; Su, Jiayu; Sagatelian, Romella; Ferrando, Adolfo A.; Ciccia, Alberto; Lan, Yanyan; Owens, David M.; Palomero, Teresa (8 January 2025). "A foundation model of transcription across human cell types". Nature. doi:10.1038/s41586-024-08391-z. ISSN 0028-0836.
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