George Lab
Cancer Genomics and Molecular Oncology
Our research focus:
The focus of our research is to understand the biological processes of cancer, and to study the evolutionary adaption of tumors under chemotherapy and immunotherapy. Emphasis is placed on tumors of the lung, and on tumors of the head and neck, which both account for the most common cancers worldwide. Recent work is focused on neuroendocrine lung tumors, of which small cell lung cancer (SCLC) is a particularly malignant lung tumor with a very poor 5-year survival rates of less than 5%. Unfortunately, to date no actionable therapeutic targets have been identified, and current treatment options include chemotherapy, and most recently a combination with immunotherapy.
Our goals:
We perform large-scale genomic and molecular profiling studies of human patient tumors in order to characterize the molecular mechanisms that determine cancer growth and progression, and therapy response. We take a multi-disciplinary approach in order to increase our knowledge on cancer. The main goal is to uncover mechanistic links to therapy efficacies, and to discover novel therapeutic approaches for cancer patients.
Our approach:
Our research methods are centered on the use of state-of-the-art technologies for genome sequencing and single cell profiling. We perform computational studies on large-scale data sets, as well as functional and molecular biological characterization of patient-derived cell culture systems and mouse models. The aim is to shed light on the genomic complexity of cancer and its impact on the micro-environment and therapy response. Our successes include the first comprehensive landmark study on the genomics of SCLC and related neuroendocrine lung tumors (George et al., Nature, 2015; George et al., Nat Communications, 2018).
Principal Investigator
Most important publications
- Poirier, John T., Julie George, Taofeek K. Owonikoko, Anton Berns, Elisabeth Brambilla, Lauren A. Byers, David Carbone, Huanhuan J. Chen, Camilla L. Christensen, Caroline Dive, Anna F. Farago, Ramaswamy Govindan, Christine Hann, Matthew D. Hellmann, Leora Horn, Jane E. Johnson, Young S. Ju, Sumin Kang, Mark Krasnow, James Lee, Se Hoon Lee, Jonathan Lehman, Benjamin Lok, Christine Lovly, David MacPherson, David McFadden, John Minna, Matthew Oser, Keunchil Park, Kwon Sik Park, Yves Pommier, Vito Quaranta, Neal Ready, Julien Sage, Giorgio Scagliotti, Martin L. Sos, Kate D. Sutherland, William D. Travis, Christopher R. Vakoc, Sarah J. Wait, Ignacio Wistuba, Kwok Kin Wong, Hua Zhang, Jillian Daigneault, Jacinta Wiens, Charles M. Rudin, and Trudy G. Oliver. “New Approaches to SCLC Therapy: From the Laboratory to the Clinic.” Journal of Thoracic Oncology 15(4):520–40, (2020)
- Rudin CM, Poirier JT, Byers LA, Dive C, Dowlati A, George J, Heymach JV, Johnson JE, Lehman JM, MacPherson D, Massion PP, Minna JD, Oliver TG, Quaranta V, Sage J, Thomas RK, Vakoc CR, Gazdar AF. Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data, Nature Reviews Cancer. 19(5):289–297, (2019)
- George J (co-corresponding), Walter V, Peifer M, Alexandrov LB, Seidel D, Leenders F, Maas L, Müller C, Dahmen I, Delhomme TM, Ardin M, Leblay N, Byrnes G, Sun R, Reynies AD, McLeer-Florin A, Bosco G,
Malchers F, Menon R, Altmüller J, Becker C, Nürnberg P, Achter V, Lang U, Schneider PM , Bogus M, Soloway MG, Wilkerson MD, Cun Y, McKay JD, Moro-Sibilot D, Brambilla CG, Lantuejoul S, Lemaitre N, Soltermann A, Weder W, Tischler V, Brustugun OT, Lund-Iversen M, Helland A, Solberg S, Ansén S, Wright G, Solomon B, Roz L, Pastorino U, Petersen I, Clement JH, Sänger J, Wolf J, Vingron M , Zander T, Perner S, Travis WD, Haas SA, Olivier M, Foll M, Büttner R, Hayes DN,
Brambilla E, Fernandez-Cuesta L, Thomas RK. Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors, Nature Communications. 13, (2018).
- Drapkin B, George J (co-first), Christensen CL, Mino-Kenudson M, Dries R, Sundaresan T, Phat S, Myers DT, Zhong J, Igo P, Hazar-Rethinam MH, Licausi JA, Gomez-Caraballo M, Kem M, Jani KN, Azimi R, Abedpour N, Menon R, Lakis S, Heist RS, Büttner R, Haas S, Sequist LV, Shaw AT, Wong K.-K., Hata AN, Toner M, Maheswaran S, Haber DA, Peifer M, Dyson N, Thomas RK, Farago AF. Genomic and functional fidelity of small cell lung cancer patient-derived xenografts, Cancer Discovery. 26, (2018).
- George J, Saito M2, Tsuta K, Iwakawa R, Shiraishi K, Scheel AH, Uchida S, Watanabe SI, Nishikawa R, Noguchi M, Peifer M, Jang SJ, Petersen I, Büttner R, Harris CC, Yokota J, Thomas RK, Kohno T, Genomic amplification of CD274 (PD-L1) in small cell lung cancer. Clinical Cancer Research. 274, (2016).
- George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, Leenders F, Lu X, Fernández-Cuesta L, Bosco G, Müller C, Dahmen I, Jahchan NS, Park KS, Yang D, Karnezis AN, Vaka D, Torres A, Wang MS, Korbel JO, Menon R, Chun SM, Kim D, Wilkerson M, Hayes N, Engelmann D, Pützer P, Bos M, Michels S, Vlasic I, Seidel D, Pinther B, Schaub P, Becker C, Janine Altmüller J, Yokota J, Kohno T, Iwakawa R, Tsuta K, Noguchi M, Muley T, Hoffmann H, Schnabel PA, Petersen I, Yuan Chen Y, Soltermann A, Tischler V, Choi CM, Kim YH, Massion PP, Zou Y, Jovanovic D, Kontic M, Wright GM, Russell PA, Solomon B, Koch I, Lindner M, Muscarella LA, la Torre A, Field JK, Jakopovic M, Knezevic J, Castaños-Vélez E, Roz L, Pastorino U, Brustugun OT, Lund-Iversen M, Thunnissen E, Köhler K, Schuler M, Botling J, Sandelin M, Sanchez-Cespedes M, Salvesen HB, Achter V, Ulrich Lang U, Bogus M, Schneider PM, Zander T, Ansén S, Hallek M, Wolf J, Vingron M, Yatabe Y, Travis WD, Nürnberg P, Reinhardt C, Perner S, Heukamp L, Büttner R, Haas SA, Brambilla E, Peifer M, Sage J, Thomas RK. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015 Aug 6;524(7563):47-53.
- M. Schultheis, A. H. Scheel, L. Ozretić, J. George (co-first), R. K. Thomas, T. Hagemann, T. Zander, J. Wolf, and R. Buettner, PD-L1 expression in small cell neuroendocrine carcinomas, European Journal of Cancer, vol. 51, no. 3, pp. 421–6, Feb. 2015.
- Fernandez-Cuesta L, Sun R, Menon R, George J, Lorenz S, Meza-Zepeda LA, Peifer M, Plenker D, Heuckmann JM, Leenders F, Zander T, Dahmen I, Koker M, Schöttle J, Ullrich RT, Altmüller J, Becker C, Nürnberg P, Seidel H, Böhm D, Göke F, Ansén S, Russell PA, Wright GM, Wainer Z, Solomon B, Petersen I, Clement JH, Sänger J, Brustugun OT, Helland Å, Solberg S, Lund-Iversen M, Buettner R, Wolf J, Brambilla E, Vingron M, Perner S, Haas SA, Thomas RK. Identification of novel fusion genes in lung cancer using breakpoint assembly of transcriptome sequencing data, Genome Biology, vol. 16, no. 1, p. 7, Jan. 2015.
- Fernandez-Cuesta L, Peifer M, Lu X, Sun R, Ozretić L, Seidel D, Zander T, Leenders F, George J, Müller C, Dahmen I, Pinther B, Bosco G, Konrad K, Altmüller J, Nürnberg P, Achter V, Lang U, Schneider PM, Bogus M, Soltermann A, Brustugun OT, Helland Å, Solberg S, Lund-Iversen M, Ansén S, Stoelben E, Wright GM, Russell P, Wainer Z, Solomon B, Field JK, Hyde R, Davies MP, Heukamp LC, Petersen I, Perner S, Lovly CM, Cappuzzo F, Travis WD, Wolf J, Vingron M, Brambilla E, Haas SA, Buettner R, Thomas RK. Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids. Nature Communications 2014 Mar 27;5:3518.
- Peifer M, Fernández-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, Plenker D, Leenders F, Sun R, Zander T, Menon R, Koker M, Dahmen I, Müller C, Di Cerbo V, Schildhaus HU, Altmüller J, Baessmann I, Becker C, de Wilde B, Vandesompele J, Böhm D, Ansén S, Gabler F, Wilkening I, Heynck S, Heuckmann JM, Lu X, Carter SL, Cibulskis K, Banerji S, Getz G, Park KS, Rauh D, Grütter C, Fischer M, Pasqualucci L, Wright G, Wainer Z, Russell P, Petersen I, Chen Y, Stoelben E, Ludwig C, Schnabel P, Hoffmann H, Muley T, Brockmann M, Engel-Riedel W, Muscarella LA, Fazio VM, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman DA, Snijders PJ, Cappuzzo F, Ligorio C, Damiani S, Field J, Solberg S, Brustugun OT, Lund-Iversen M, Sänger J, Clement JH, Soltermann A, Moch H, Weder W, Solomon B, Soria JC, Validire P, Besse B, Brambilla E, Brambilla C, Lantuejoul S, Lorimier P, Schneider PM, Hallek M, Pao W, Meyerson M, Sage J, Shendure J, Schneider R, Büttner R, Wolf J, Nürnberg P, Perner S, Heukamp LC, Brindle PK, Haas S, and Thomas RK. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nature Genetics 2012 Oct;44(10):1104-10.