Roel Verhaak, PhD
Professor of Neurosurgery; Professor, Department of Neurosurgery
Research & Publications
Biography
Locations
Research Summary
We are a cancer biology lab with a research focus on brain tumors and gliomas/glioblastomas in particular. We study the processes of glioma-related tumor evolution and treatment resistance. We use high-throughput sequencing, computational analysis and functional studies in our research. We have previously identified extrachromosomal oncogene DNA amplifications as playing a particularly important role in tumor evolution of not just gliomas, but all cancers. We are developing new therapies for cancer through targeting of extrachromosomal DNA amplifications.
Coauthors
Research Interests
Astrocytoma; Glioblastoma; Oligodendroglioma; Diffuse Intrinsic Pontine Glioma
Public Health Interests
Cancer; Genetics, Genomics, Epigenetics
Selected Publications
- Extrachromosomal DNA amplifications in cancerYi E, Chamorro González R, Henssen A, Verhaak R. Extrachromosomal DNA amplifications in cancer. Nature Reviews Genetics 2022, 23: 760-771. PMID: 35953594, PMCID: PMC9671848, DOI: 10.1038/s41576-022-00521-5.
- Glioma progression is shaped by genetic evolution and microenvironment interactionsVarn F, Johnson K, Martinek J, Huse J, Nasrallah M, Wesseling P, Cooper L, Malta T, Wade T, Sabedot T, Brat D, Gould P, Wöehrer A, Aldape K, Ismail A, Sivajothi S, Barthel F, Kim H, Kocakavuk E, Ahmed N, White K, Datta I, Moon H, Pollock S, Goldfarb C, Lee G, Garofano L, Anderson K, Nehar-Belaid D, Barnholtz-Sloan J, Bakas S, Byrne A, D’Angelo F, Gan H, Khasraw M, Migliozzi S, Ormond D, Paek S, Van Meir E, Walenkamp A, Watts C, Weiss T, Weller M, Palucka K, Stead L, Poisson L, Noushmehr H, Iavarone A, Verhaak R, Consortium T, Varn F, Johnson K, Martinek J, Huse J, Nasrallah M, Wesseling P, Cooper L, Malta T, Wade T, Sabedot T, Brat D, Gould P, Wöehrer A, Aldape K, Ismail A, Sivajothi S, Barthel F, Kim H, Kocakavuk E, Ahmed N, White K, Datta I, Moon H, Pollock S, Goldfarb C, Lee G, Garofano L, Anderson K, Nehar-Belaid D, Barnholtz-Sloan J, Bakas S, Byrne A, D’Angelo F, Gan H, Khasraw M, Migliozzi S, Ormond D, Paek S, Van Meir E, Walenkamp A, Watts C, Weiss T, Weller M, Alfaro K, Amin S, Ashley D, Bock C, Brodbelt A, Bulsara K, Castro A, Connelly J, Costello J, de Groot J, Finocchiaro G, French P, Golebiewska A, Hau A, Hong C, Horbinski C, Kannan K, Kouwenhoven M, Lasorella A, LaViolette P, Ligon K, Lowman A, Mehta S, Miletic H, Molinaro A, Ng H, Niclou S, Niers J, Phillips J, Rabadan R, Rao G, Reifenberger G, Sanai N, Short S, Smitt P, Sloan A, Smits M, Snyder J, Suzuki H, Tabatabai G, Tanner G, Tomaszewski W, Wells M, Westerman B, Wheeler H, Xie J, Yung W, Zadeh G, Zhao J, Palucka K, Stead L, Poisson L, Noushmehr H, Iavarone A, Verhaak R. Glioma progression is shaped by genetic evolution and microenvironment interactions. Cell 2022, 185: 2184-2199.e16. PMID: 35649412, PMCID: PMC9189056, DOI: 10.1016/j.cell.2022.04.038.
- Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress responseJohnson K, Anderson K, Courtois E, Gujar A, Barthel F, Varn F, Luo D, Seignon M, Yi E, Kim H, Estecio M, Zhao D, Tang M, Navin N, Maurya R, Ngan C, Verburg N, de Witt Hamer P, Bulsara K, Samuels M, Das S, Robson P, Verhaak R. Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response. Nature Genetics 2021, 53: 1456-1468. PMID: 34594038, PMCID: PMC8570135, DOI: 10.1038/s41588-021-00926-8.
- Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancersKim H, Nguyen N, Turner K, Wu S, Gujar A, Luebeck J, Liu J, Deshpande V, Rajkumar U, Namburi S, Amin S, Yi E, Menghi F, Schulte J, Henssen A, Chang H, Beck C, Mischel P, Bafna V, Verhaak R. Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Nature Genetics 2020, 52: 891-897. PMID: 32807987, PMCID: PMC7484012, DOI: 10.1038/s41588-020-0678-2.
- Longitudinal molecular trajectories of diffuse glioma in adultsBarthel FP, Johnson KC, Varn FS, Moskalik AD, Tanner G, Kocakavuk E, Anderson KJ, Abiola O, Aldape K, Alfaro KD, Alpar D, Amin SB, Ashley DM, Bandopadhayay P, Barnholtz-Sloan JS, Beroukhim R, Bock C, Brastianos PK, Brat DJ, Brodbelt AR, Bruns AF, Bulsara KR, Chakrabarty A, Chakravarti A, Chuang JH, Claus EB, Cochran EJ, Connelly J, Costello JF, Finocchiaro G, Fletcher MN, French PJ, Gan HK, Gilbert MR, Gould PV, Grimmer MR, Iavarone A, Ismail A, Jenkinson MD, Khasraw M, Kim H, Kouwenhoven MCM, LaViolette PS, Li M, Lichter P, Ligon KL, Lowman AK, Malta TM, Mazor T, McDonald KL, Molinaro AM, Nam DH, Nayyar N, Ng HK, Ngan CY, Niclou SP, Niers JM, Noushmehr H, Noorbakhsh J, Ormond DR, Park CK, Poisson LM, Rabadan R, Radlwimmer B, Rao G, Reifenberger G, Sa JK, Schuster M, Shaw BL, Short SC, Smitt PAS, Sloan AE, Smits M, Suzuki H, Tabatabai G, Van Meir EG, Watts C, Weller M, Wesseling P, Westerman BA, Widhalm G, Woehrer A, Yung WKA, Zadeh G, Huse JT, De Groot JF, Stead LF, Verhaak RGW. Longitudinal molecular trajectories of diffuse glioma in adults. Nature 2019, 576: 112-120. PMID: 31748746, PMCID: PMC6897368, DOI: 10.1038/s41586-019-1775-1.
- NUTMEG: A randomized phase II study of nivolumab and temozolomide versus temozolomide alone in newly diagnosed older patients with glioblastomaSim H, Wachsmuth L, Barnes E, Yip S, Koh E, Hall M, Jennens R, Ashley D, Verhaak R, Heimberger A, Rosenthal M, Hovey E, Ellingson B, Tognela A, Gan H, Wheeler H, Back M, McDonald K, Long A, Cuff K, Begbie S, Gedye C, Mislang A, Le H, Johnson M, Kong B, Simes J, Lwin Z, Khasraw M. NUTMEG: A randomized phase II study of nivolumab and temozolomide versus temozolomide alone in newly diagnosed older patients with glioblastoma. Neuro-Oncology Advances 2023, 5: vdad124. PMID: 37841696, PMCID: PMC10576515, DOI: 10.1093/noajnl/vdad124.
- Hemizygous CDKN2A deletion confers worse survival outcomes in IDHmut-noncodel gliomasKocakavuk E, Johnson K, Sabedot T, Reinhardt H, Noushmehr H, Verhaak R. Hemizygous CDKN2A deletion confers worse survival outcomes in IDHmut-noncodel gliomas. Neuro-Oncology 2023, 25: 1721-1723. PMID: 37329568, PMCID: PMC10479907, DOI: 10.1093/neuonc/noad095.
- Live-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in CancerYi E, Gujar A, Guthrie M, Kim H, Zhao D, Johnson K, Amin S, Costa M, Yu Q, Das S, Jillette N, Clow P, Cheng A, Verhaak R. Live-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer. Cancer Discovery 2022, 12: 468-483. PMID: 34819316, PMCID: PMC8831456, DOI: 10.1158/2159-8290.cd-21-1376.
- Spatial concordance of DNA methylation classification in diffuse gliomaVerburg N, Barthel F, Anderson K, Johnson K, Koopman T, Yaqub M, Hoekstra O, Lammertsma A, Barkhof F, Pouwels P, Reijneveld J, Rozemuller A, Beliën J, Boellaard R, Taylor M, Das S, Costello J, Vandertop W, Wesseling P, de Witt Hamer P, Verhaak R. Spatial concordance of DNA methylation classification in diffuse glioma. Neuro-Oncology 2021, 23: 2054-2065. PMID: 34049406, PMCID: PMC8643482, DOI: 10.1093/neuonc/noab134.
- Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancerKocakavuk E, Anderson K, Varn F, Johnson K, Amin S, Sulman E, Lolkema M, Barthel F, Verhaak R. Radiotherapy is associated with a deletion signature that contributes to poor outcomes in patients with cancer. Nature Genetics 2021, 53: 1088-1096. PMID: 34045764, PMCID: PMC8483261, DOI: 10.1038/s41588-021-00874-3.
- Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcriptionZhu Y, Gujar A, Wong C, Tjong H, Ngan C, Gong L, Chen Y, Kim H, Liu J, Li M, Mil-Homens A, Maurya R, Kuhlberg C, Sun F, Yi E, deCarvalho A, Ruan Y, Verhaak R, Wei C. Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription. Cancer Cell 2021, 39: 694-707.e7. PMID: 33836152, PMCID: PMC8119378, DOI: 10.1016/j.ccell.2021.03.006.
- Comparative Molecular Life History of Spontaneous Canine and Human GliomasAmin S, Anderson K, Boudreau C, Martinez-Ledesma E, Kocakavuk E, Johnson K, Barthel F, Varn F, Kassab C, Ling X, Kim H, Barter M, Lau C, Ngan C, Chapman M, Koehler J, Long J, Miller A, Miller C, Porter B, Rissi D, Mazcko C, LeBlanc A, Dickinson P, Packer R, Taylor A, Rossmeisl J, Woolard K, Heimberger A, Levine J, Verhaak R. Comparative Molecular Life History of Spontaneous Canine and Human Gliomas. Cancer Cell 2020, 37: 243-257.e7. PMID: 32049048, PMCID: PMC7132629, DOI: 10.1016/j.ccell.2020.01.004.
- Extrachromosomal oncogene amplification in tumour pathogenesis and evolutionVerhaak R, Bafna V, Mischel P. Extrachromosomal oncogene amplification in tumour pathogenesis and evolution. Nature Reviews Cancer 2019, 19: 283-288. PMID: 30872802, PMCID: PMC7168519, DOI: 10.1038/s41568-019-0128-6.
- Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastomadeCarvalho A, Kim H, Poisson L, Winn M, Mueller C, Cherba D, Koeman J, Seth S, Protopopov A, Felicella M, Zheng S, Multani A, Jiang Y, Zhang J, Nam D, Petricoin E, Chin L, Mikkelsen T, Verhaak R. Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma. Nature Genetics 2018, 50: 708-717. PMID: 29686388, PMCID: PMC5934307, DOI: 10.1038/s41588-018-0105-0.
- TumorFusions: an integrative resource for cancer-associated transcript fusionsHu X, Wang Q, Tang M, Barthel F, Amin S, Yoshihara K, Lang F, Martinez-Ledesma E, Lee S, Zheng S, Verhaak R. TumorFusions: an integrative resource for cancer-associated transcript fusions. Nucleic Acids Research 2017, 46: gkx1018-. PMID: 29099951, PMCID: PMC5753333, DOI: 10.1093/nar/gkx1018.
- Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the MicroenvironmentWang Q, Hu B, Hu X, Kim H, Squatrito M, Scarpace L, deCarvalho A, Lyu S, Li P, Li Y, Barthel F, Cho H, Lin Y, Satani N, Martinez-Ledesma E, Zheng S, Chang E, Sauvé C, Olar A, Lan Z, Finocchiaro G, Phillips J, Berger M, Gabrusiewicz K, Wang G, Eskilsson E, Hu J, Mikkelsen T, DePinho R, Muller F, Heimberger A, Sulman E, Nam D, Verhaak R. Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. Cancer Cell 2017, 32: 42-56.e6. PMID: 28697342, PMCID: PMC5599156, DOI: 10.1016/j.ccell.2017.06.003.
- Studying a Complex TumorZheng S, Chheda M, Verhaak R. Studying a Complex Tumor. The Cancer Journal 2012, 18: 107-114. PMID: 22290264, PMCID: PMC3342695, DOI: 10.1097/ppo.0b013e3182431c57.