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

Rani E. George, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Associate 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

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  • 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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