Photo of Rani E. George, MD, PhD

Rani E. George, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-5281


rani_george@dfci.harvard.edu

Photo of Rani E. George, MD, PhD

Dana-Farber Cancer Institute
Phone: (617) 632-5281


rani_george@dfci.harvard.edu

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Rani E. George, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Pediatrics, Harvard Medical School
  • Attending Physician, Pediatric Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

I am a physician scientist with a major focus on two aspects of the pediatric solid tumor neuroblastoma, identifying molecular targets that can be translated into novel therapies and understanding the perturbations that occur during development to drive neuroblastoma initiation and progression. Following our recent discovery of activating, small-molecule inhibitor-sensitive somatic mutations in the ALK tyrosine kinase in primary tumors, we are investigating mechanisms of ALK activation and regulation in neuroblastoma as well as strategies to inhibit ALK activity that can be used therapeutically. The translational research program in my laboratory integrates basic developmental and cancer biology, genome-wide analysis of tumor samples, drug development and clinical trials targeting molecular aberrations in neuroblastoma. The second focus of my laboratory is understanding the development of the sympathetic nervous system, with particular emphasis on the PHOX2B transcription factor, a master regulator of noradrenergic differentiation and a gene that is mutated in congenital neuroblastomas. Using both zebrafish and cell culture systems the effects of mutant PHOX2B and its interactions are being investigated.

Publications from Harvard Catalyst Profiles

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  • Huang H, Gont A, Kee L, Dries R, Pfeifer K, Sharma B, Debruyne DN, Harlow M, Sengupta S, Guan J, Yeung CM, Wang W, Hallberg B, Palmer RH, Irwin MS, George RE. Extracellular domain shedding of the ALK receptor mediates neuroblastoma cell migration. Cell Rep 2021; 36:109363. PubMed
  • Dries R, Zhu Q, Dong R, Eng CL, Li H, Liu K, Fu Y, Zhao T, Sarkar A, Bao F, George RE, Pierson N, Cai L, Yuan GC. Giotto: a toolbox for integrative analysis and visualization of spatial expression data. Genome Biol 2021; 22:78. PubMed
  • Gao Y, Volegova M, Nasholm N, Das S, Kwiatkowski N, Abraham BJ, Zhang T, Gray NS, Gustafson C, Krajewska M, George RE. Synergistic Anti-Tumor Effect of Combining Selective CDK7 and BRD4 Inhibition in Neuroblastoma. 2021; 11:773186. PubMed
  • Moreno L, Barone G, DuBois SG, Molenaar J, Fischer M, Schulte J, Eggert A, Schleiermacher G, Speleman F, Chesler L, Geoerger B, Hogarty MD, Irwin MS, Bird N, Blanchard GB, Buckland S, Caron H, Davis S, De Wilde B, Deubzer HE, Dolman E, Eilers M, George RE, George S, Jaroslav Š, Maris JM, Marshall L, Merchant M, Mortimer P, Owens C, Philpott A, Poon E, Shay JW, Tonelli R, Valteau-Couanet D, Vassal G, Park JR, Pearson ADJ. Accelerating drug development for neuroblastoma: Summary of the Second Neuroblastoma Drug Development Strategy forum from Innovative Therapies for Children with Cancer and International Society of Paediatric Oncology Europe Neuroblastoma. Eur J Cancer 2020; 136:52-68. PubMed
  • Cohen MA, Zhang S, Sengupta S, Ma H, Bell GW, Horton B, Sharma B, George RE, Spranger S, Jaenisch R. Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras. Cell Stem Cell 2020. PubMed
  • Zeineldin M, Federico S, Chen X, Fan Y, Xu B, Stewart E, Zhou X, Jeon J, Griffiths L, Nguyen R, Norrie J, Easton J, Mulder H, Yergeau D, Liu Y, Wu J, Van Ryn C, Naranjo A, Hogarty MD, Kamiński MM, Valentine M, Pruett-Miller SM, Pappo A, Zhang J, Clay MR, Bahrami A, Vogel P, Lee S, Shelat A, Sarthy JF, Meers MP, George RE, Mardis ER, Wilson RK, Henikoff S, Downing JR, Dyer MA. MYCN amplification and ATRX mutations are incompatible in neuroblastoma. Nat Commun 2020; 11:913. PubMed
  • Murphy AJ, Chen X, Pinto EM, Williams JS, Clay MR, Pounds SB, Cao X, Shi L, Lin T, Neale G, Morton CL, Woolard MA, Mulder HL, Gil HJ, Rehg JE, Billups CA, Harlow ML, Dome JS, Houghton PJ, Easton J, Zhang J, George RE, Zambetti GP, Davidoff AM. Forty-five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor. Nat Commun 2019; 10:5806. PubMed
  • Bayles I, Krajewska M, Pontius WD, Saiakhova A, Morrow JJ, Bartels C, Lu J, Faber ZJ, Fedorov Y, Hong ES, Karnuta JM, Rubin B, Adams DJ, George RE, Scacheri PC. Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma. J Clin Invest 2019; 129:4377-4392. PubMed
  • Debruyne DN, Dries R, Sengupta S, Seruggia D, Gao Y, Sharma B, Huang H, Moreau L, McLane M, Day DS, Marco E, Chen T, Gray NS, Wong KK, Orkin SH, Yuan GC, Young RA, George RE. BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells. Nature 2019; 572:676-680. PubMed
  • Wong M, Sun Y, Xi Z, Milazzo G, Poulos RC, Bartenhagen C, Bell JL, Mayoh C, Ho N, Tee AE, Chen X, Li Y, Ciaccio R, Liu PY, Jiang CC, Lan Q, Jayatilleke N, Cheung BB, Haber M, Norris MD, Zhang XD, Marshall GM, Wang JY, Hüttelmaier S, Fischer M, Wong JWH, Xu H, Perini G, Dong Q, George RE, Liu T. JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma. Nat Commun 2019; 10:3319. PubMed
  • Krajewska M, Dries R, Grassetti AV, Dust S, Gao Y, Huang H, Sharma B, Day DS, Kwiatkowski N, Pomaville M, Dodd O, Chipumuro E, Zhang T, Greenleaf AL, Yuan GC, Gray NS, Young RA, Geyer M, Gerber SA, George RE. CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation. Nat Commun 2019; 10:1757. PubMed
  • Choe J, Lin S, Zhang W, Liu Q, Wang L, Ramirez-Moya J, Du P, Kim W, Tang S, Sliz P, Santisteban P, George RE, Richards WG, Wong KK, Locker N, Slack FJ, Gregory RI. mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis. Nature 2018; 561:556-560. PubMed
  • Powell CE, Gao Y, Tan L, Donovan KA, Nowak RP, Loehr A, Bahcall M, Fischer ES, Jänne PA, George RE, Gray NS. Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK). J Med Chem 2018; 61:4249-4255. PubMed
  • Gao Y, Zhang T, Terai H, Ficarro SB, Kwiatkowski N, Hao MF, Sharma B, Christensen CL, Chipumuro E, Wong KK, Marto JA, Hammerman PS, Gray NS, George RE. Overcoming Resistance to the THZ Series of Covalent Transcriptional CDK Inhibitors. Cell Chem Biol 2017. PubMed
  • Sengupta S, George RE. Super-Enhancer-Driven Transcriptional Dependencies in Cancer. Trends Cancer 2017; 3:269-281. PubMed
  • Sun M, Ha N, Pham DH, Frederick M, Sharma B, Naruse C, Asano M, Pipkin ME, George RE, Thai TH. Cbx3/HP1γ deficiency confers enhanced tumor-killing capacity on CD8(+) T cells. Sci Rep 2017; 7:42888. PubMed
  • Carter DR, Sutton SK, Pajic M, Murray J, Sekyere EO, Fletcher J, Beckers A, De Preter K, Speleman F, George RE, Haber M, Norris MD, Cheung BB, Marshall GM. Glutathione biosynthesis is upregulated at the initiation of MYCN-driven neuroblastoma tumorigenesis. Mol Oncol 2016. PubMed
  • Versteeg R, George RE. Targeting ALK: The Ten Lives of a Tumor. 2016; 6:20-1. PubMed
  • Hatcher JM, Bahcall M, Choi HG, Gao Y, Sim T, George R, Jänne PA, Gray NS. Discovery of Inhibitors That Overcome the G1202R Anaplastic Lymphoma Kinase Resistance Mutation. J Med Chem 2015; 58:9296-308. PubMed
  • Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA, Molenaar JJ, Versteeg R. TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors. Nat Genet 2015; 47:1411-4. PubMed
  • George RE. Seek and Ye Shall Find: Subclonal Anaplastic Lymphoma Kinase Mutations. Clin Cancer Res 2015. PubMed
  • Krishnadas DK, Shusterman S, Bai F, Diller L, Sullivan JE, Cheerva AC, George RE, Lucas KG. A phase I trial combining decitabine/dendritic cell vaccine targeting MAGE-A1, MAGE-A3 and NY-ESO-1 for children with relapsed or therapy-refractory neuroblastoma and sarcoma. Cancer Immunol Immunother 2015. PubMed
  • Christensen CL, Kwiatkowski N, Abraham BJ, Carretero J, Al-Shahrour F, Zhang T, Chipumuro E, Herter-Sprie GS, Akbay EA, Altabef A, Zhang J, Shimamura T, Capelletti M, Reibel JB, Cavanaugh JD, Gao P, Liu Y, Michaelsen SR, Poulsen HS, Aref AR, Barbie DA, Bradner JE, George RE, Gray NS, Young RA, Wong KK. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. Cancer Cell 2014; 26:909-22. PubMed
  • Chipumuro E, Marco E, Christensen CL, Kwiatkowski N, Zhang T, Hatheway CM, Abraham BJ, Sharma B, Yeung C, Altabef A, Perez-Atayde A, Wong KK, Yuan GC, Gray NS, Young RA, George RE. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell 2014; 159:1126-39. PubMed
  • Moore NF, Azarova AM, Bhatnagar N, Ross KN, Drake LE, Frumm S, Liu QS, Christie AL, Sanda T, Chesler L, Kung AL, Gray NS, Stegmaier K, George RE. Molecular rationale for the use of PI3K/AKT/mTOR pathway inhibitors in combination with crizotinib in ALK-mutated neuroblastoma. 2014; 5:8737-49. PubMed
  • Jamin Y, Glass L, Hallsworth A, George R, Koh DM, Pearson AD, Chesler L, Robinson SP. Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma. PLoS ONE 2014; 9:e92886. PubMed
  • Pei D, Luther W, Wang W, Paw BH, Stewart RA, George RE. Distinct neuroblastoma-associated alterations of PHOX2B impair sympathetic neuronal differentiation in zebrafish models. PLoS Genet. 2013; 9:e1003533. PubMed
  • Berry T, Luther W, Bhatnagar N, Jamin Y, Poon E, Sanda T, Pei D, Sharma B, Vetharoy WR, Hallsworth A, Ahmad Z, Barker K, Moreau L, Webber H, Wang W, Liu Q, Perez-Atayde A, Rodig S, Cheung NK, Raynaud F, Hallberg B, Robinson SP, Gray NS, Pearson AD, Eccles SA, Chesler L, George RE. The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell 2012; 22:117-30. PubMed
  • Garcia I, Mayol G, Rodriguez E, Sunol M, Gershon TR, Rios J, Cheung NK, Kieran MW, George RE, Perez-Atayde AR, Casala C, Galvan P, de Torres C, Mora J, Lavarino C. Expression of the neuron-specific protein CHD5 is an independent marker of outcome in neuroblastoma. Mol Cancer 2010; 9:277. PubMed
  • George RE, Lahti JM, Adamson PC, Zhu K, Finkelstein D, Ingle AM, Reid JM, Krailo M, Neuberg D, Blaney SM, Diller L. Phase I study of decitabine with doxorubicin and cyclophosphamide in children with neuroblastoma and other solid tumors: a Children's Oncology Group study. Pediatr Blood Cancer 2010; 55:629-38. PubMed
  • George RE, Diller L, Bernstein ML. Pharmacotherapy of neuroblastoma. Expert Opin Pharmacother 2010; 11:1467-78. PubMed
  • Volchenboum SL,Li C,Li S,Attiyeh EF,Reynolds CP,Maris JM,Look AT,George RE. Comparison of primary neuroblastoma tumors and derivative early-passage cell lines using genome-wide single nucleotide polymorphism array analysis. Cancer Res 2009; 69:4143-9. PubMed
  • George RE,Sanda T,Hanna M,Frohling S,Luther W 2nd,Zhang J,Ahn Y,Zhou W,London WB,McGrady P,Xue L,Zozulya S,Gregor VE,Webb TR,Gray NS,Gilliland DG,Diller L,Greulich H,Morris SW,Meyerson M,Look AT. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 2008; 455:975-8. PubMed
  • George RE, Attiyeh EF, Li S, Moreau LA, Neuberg D, Li C, Fox EA, Meyerson M, Diller L, Fortina P, Look AT, Maris JM. Genome-Wide Analysis of Neuroblastomas using High-Density Single Nucleotide Polymorphism Arrays. PLoS ONE 2007; 2:e255. PubMed
  • George RE, Li S, Medeiros-Nancarrow C, Neuberg D, Marcus K, Shamberger RC, Pulsipher M, Grupp SA, Diller L. High-risk neuroblastoma treated with tandem autologous peripheral-blood stem cell-supported transplantation: long-term survival update. J Clin Oncol 2006; 24:2891-6. PubMed
  • Stewart RA, Arduini BL, Berghmans S, George RE, Kanki JP, Henion PD, Look AT. Zebrafish foxd3 is selectively required for neural crest specification, migration and survival. Dev Biol 2006; 292:174-88. PubMed
  • George RE, London WB, Cohn SL, Maris JM, Kretschmar C, Diller L, Brodeur GM, Castleberry RP, Look AT. Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol 2005; 23:6466-73. PubMed
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DF/HCC members that share similar concepts* with Rani E. George, MD, PhD but have yet to coauthor a publication with this researcher.

* Concepts are MeSH terms, automatically derived from member publications

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