BBS Faculty Member - Rani George

Rani George

Department of Pediatric Hematology/Oncology

Dana Farber Cancer Institute
Department of Pediatric Oncology, Dana 640E
450 Brookline Ave.
Boston, MA 02215
Tel: 617-632-5281
Fax: 617-632-4850
Visit my lab page here.

Our laboratory is focused on studying neuroblastoma, an embryonically derived pediatric tumor of the peripheral sympathetic nervous system. We are interested in the following general areas: 1) identifying molecular targets that can be translated into novel therapies in metastatic neuroblastoma, and 2) unraveling the genetic perturbations that occur during development of the sympathetic nervous system and underlie neuroblastoma initiation and progression.

We identified activating, somatic mutations in the ALK tyrosine kinase receptor in neuroblastoma that are sensitive to small molecule inhibitors. Our laboratory is currently investigating mechanisms of ALK receptor activation and regulation in this disease with the ultimate goal of developing strategies to inhibit ALK-driven pathways. The anti-apoptotic role of the activated ALK kinase is an active area of investigation in our laboratory.

A second focus of the laboratory is exploring ways of inhibiting deregulated
MYCN, an oncogenic transcription factor that is frequently amplified in high-risk neuroblastoma, by targeting pathways that are synthetic lethal to its function. These studies stem from the finding that mutated ALK accelerates MYCN-induced neuroblastoma by activating key signaling cascades and that combined inhibition of ALK and downstream signaling leads to tumor regression and prolongation of survival.

Thirdly, we are studying the early perturbations that occur during sympathetic neuronal development, specifically focusing on mutant ALK and PHOX2B, both of which have been observed in familial neuroblastoma. Native ALK is mainly expressed in the developing central and peripheral nervous systems and is thought to function as a dependence receptor to trigger apoptosis. Using
ALK-driven transgenic animal models that develop neuroblastoma and those that are deficient in ALK, we are dissecting the early molecular changes that occur during tumorigenesis. The effects of PHOX2B mutations on neuronal differentiation and alterations in protein-protein interaction networks are also being investigated.

The translational research program in our laboratory integrates cancer biology, pre-clinical drug development and clinical trials targeting molecular aberrations in neuroblastoma. Our laboratory research has informed the design and implementation of clinical trials for relapsed neuroblastoma and other solid tumors.

Last Update: 7/25/2014


For a complete listing of publications click here.



George RE, Sanda T, Hanna M, Frohling S, Luther II W, Jianming Z, Ahn Y, Zhou W, London WB, McGrady P, Xue L, Zozulya S, Gregory 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, 455(7215):975-8, 2008. PMID: 18923525.

Azarova AM, Gautam G,
George RE. Emerging importance of ALK in neuroblastoma. Seminars in Cancer Biology, 2011; 21(4):267-75. PMID: 21945349.

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 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, 2012 Jul 10; 22(1):117-30.

Pei D, Luther W, Wang W, Paw BH, Stewart RA,
George RE. Neuroblastoma-associated PHOX2B mutations impair sympathetic neuronal differentiation. (PLOS Genetics, in press).

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