Rani George, MD, PhD

Research Overview

Dr. George is 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 the identification of activating mutations in the ALK tyrosine kinase receptor in neuroblastoma by Dr George and colleagues, her laboratory is investigating mechanisms of ALK activation and regulation in neuroblastoma as well as strategies to inhibit ALK that can be used therapeutically. The second focus of Dr. George’s laboratory is to better understand 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 hereditary neuroblastomas. Thirdly, Dr George's group is interested in studying the resistance mechanisms that lead to relapsed neuroblastoma and in developing early phase clinical trials for these patients. The translational research program in Dr. George’s laboratory integrates basic developmental and cancer biology, pre-clinical drug development and clinical trials targeting molecular aberrations in neuroblastoma.

About Rani George

Dr. George attended medical school at A.M. Dogliotti College of Medicine, University of Liberia. She trained in pediatrics and received her PhD in cancer biology from the University of Newcastle-upon-Tyne, UK. She completed a fellowship in Pediatric Hematology/Oncology at Children’s Hospital Boston/Dana-Farber Cancer Institute. Dr. George completed her residency as a member of the Boston Combined Residency Program in Pediatrics. Research in Dr George's laboratory is funded by the National Institutes of Health, The Sidney Kimmel Foundation and the American Cancer Society.

Key Publications

• Berry, T, Luther W. Bhatnagar N, Jamin Y, Poon E, Sanda T, PeiD, Sharma B, Vetharoy WR, Hallsworth A, Ahmad Z, Barker K, Moreau L, Webber H, Wang W, Liu Q, Perez-Atayde A, Rodig S, Cheung N-K, Raynaud F, Hallberg B, Robinson SP, Gray NS, Pearson ADJ, Eccles SA, Chesler L?, George RE?. The ALKF1174L mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell 22, 117–130, 2012

• Matthay KK, George RE, Yu AL. Promising therapeutic targets in neuroblastoma. Clinical Cancer Research 18(10):2740-53, 2012.

• Zhu S, Lee JS, Guo F, Shin J, Perez-Atayde AR, Kutok JL, Rodig SJ, Neuberg DS, Helman D, Feng H, Stewart RA, Wang W, George RE, Kanki JP, Look AT. Activated ALK Collaborates with MYCN in Neuroblastoma Pathogenesis. Cancer Cell 21(3):362-373, 2012.

• George RE, Perez-Atayde AR, MD, Yao X, London WB, Shamberger RC, Neuberg D, Diller, L. Tumor Histology during Induction Therapy in Patients with High-Risk Neuroblastoma. Pediatric Blood and Cancer, 2011 Dec 11. [Epub ahead of print].
   
• AzarovaAM, Gautam G, George RE.  Emerging importance of ALK in neuroblastoma. Seminars in Cancer Biology, Semin Cancer Biol. 2011 Sep 16. [Epub ahead of print]. PMID: 21945349.

• Deng X, Wang J, Zhang J, Sim T, Kim ND, Sasaki T, Luther W 2nd, George RE, Jänne PA, Gray NS.  Discovery of 3, 5-Diamino-1, 2, 4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors.  ACS Med Chem Lett. 2(5):379-384, 2011.

• George RE, Lahti J M, Zhu K, Finkelstein D, Ingle AM, Reid J M, Krailo M, Neuberg D, Adamson P C, Blaney SM, Diller Lisa. Phase I Study of Decitabine in Combination with Doxorubicin and Cyclophosphamide in Children with Neuroblastoma and Other Solid Tumors - A Children’s Oncology Group Phase 1 Consortium Study. Pediatric Blood and Cancer, 55(4):629-38, 2010. PMID: 20589651.

• 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 Research. 2009 May 15;69(10):41

• 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 October 16;455(7215):883-4.

• 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.

• Moreau LA, McGrady P, London WB, Shimada H, Cohn SL, Maris JM, Diller L, Look AT, George RE. Does MYCN Amplification Manifested as Homogenously Staining Regions at Diagnosis Predict a Worse Outcome in Children with Neuroblastoma? A Children’s Oncology Group Study. Clin Cancer Res. 12:5693-7, 2006.

• 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. Journal of Clinical Oncology. 2006 Jun 20;24 (18) 2891-6

• 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. Developmental Biology. 2006 Apr 1;292(1):174-88.

• 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. Journal of Clinical Oncology. 2005 Sep 20; 23(27):6443-4.

• George RE, Lipshultz SE, Lipsitz SR, Colan SD, Diller Lisa. Association between congenital cardiovascular malformations and neuroblastoma. J. Pediatr: 2004; 144:444-8.