Photo of Xandra O. Breakefield,  PhD

Xandra O. Breakefield, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-5728
Fax: (617) 724-1537


breakefield@hms.harvard.edu

Xandra O. Breakefield, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Professor, Neurology, Harvard Medical School
  • Geneticist (Neurology), Molecular Neurogenetics Unit, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Breakefield laboratory is focusing on the use of molecular genetics to elucidate the genes underlying glioblastoma and to develop gene therapy strategies for brain tumors and schwannomas in the peripheral nervous system. This work involves development of novel vectors to enhance gene delivery/expression in tumors, and exploration of combined therapeutic modalities. We have used a number of viral vectors for gene delivery in culture and in vivo, and explored the nucleic acid content of extracellular vesicles (exosomes and microvesicles) released by neural cells, including their use as biomarkers in the serum and cerebral spinal fluid for brain tumors, ability to carry out intercellular communication among cells, and capacity to serve as therapeutic agents.

Publications

Powered by Harvard Catalyst
  • Gong Y, Mu D, Prabhakar S, Moser A, Musolino P, Ren J, Breakefield XO, Maguire CA, Eichler FS. Adenoassociated Virus Serotype 9-Mediated Gene Therapy for X-Linked Adrenoleukodystrophy. Mol Ther 2015. PubMed
  • Redzic JS, Balaj L, van der Vos KE, Breakefield XO. Extracellular RNA mediates and marks cancer progression. Semin Cancer Biol 2014. PubMed
  • Vader P, Breakefield XO, Wood MJ. Extracellular vesicles: emerging targets for cancer therapy. Trends Mol Med 2014. PubMed
  • Lai CP, Mardini O, Ericsson M, Prabhakar S, Maguire CA, Chen JW, Tannous BA, Breakefield XO. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano 2014; 8:483-94. PubMed
  • Lai CP, Tannous BA, Breakefield XO. Noninvasive in vivo monitoring of extracellular vesicles. Methods Mol Biol 2013; 1098:249-58. PubMed
  • Atai NA, Balaj L, van Veen H, Breakefield XO, Jarzyna PA, Van Noorden CJ, Skog J, Maguire CA. Heparin blocks transfer of extracellular vesicles between donor and recipient cells. J. Neurooncol. 2013; 115:343-51. PubMed
  • EL Andaloussi S, Mäger I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov 2013; 12:347-57. PubMed
  • Prabhakar S, Taherian M, Gianni D, Conlon TJ, Fulci G, Brockmann J, Stemmer-Rachamimov A, Sena-Esteves M, Breakefield XO, Brenner GJ. Regression of schwannomas induced by adeno-associated virus-mediated delivery of caspase-1. Hum Gene Ther 2013; 24:152-62. PubMed
  • Chen WW, Balaj L, Liau LM, Samuels ML, Kotsopoulos SK, Maguire CA, Loguidice L, Soto H, Garrett M, Zhu LD, Sivaraman S, Chen C, Wong ET, Carter BS, Hochberg FH, Breakefield XO, Skog J. BEAMing and Droplet Digital PCR Analysis of Mutant IDH1 mRNA in Glioma Patient Serum and Cerebrospinal Fluid Extracellular Vesicles. Mol Ther Nucleic Acids 2013; 2:e109. PubMed
  • Akers JC, Ramakrishnan V, Kim R, Skog J, Nakano I, Pingle S, Kalinina J, Hua W, Kesari S, Mao Y, Breakefield XO, Hochberg FH, Van Meir EG, Carter BS, Chen CC. MiR-21 in the extracellular vesicles (EVs) of cerebrospinal fluid (CSF): a platform for glioblastoma biomarker development. PLoS ONE 2013; 8:e78115. PubMed
  • Prabhakar S, Goto J, Zhang X, Sena-Esteves M, Bronson R, Brockmann J, Gianni D, Wojtkiewicz GR, Chen JW, Stemmer-Rachamimov A, Kwiatkowski DJ, Breakefield XO. Correction: Stochastic Model of Tsc1 Lesions in Mouse Brain. PLoS ONE 2013. PubMed
  • Shao H, Chung J, Balaj L, Charest A, Bigner DD, Carter BS, Hochberg FH, Breakefield XO, Weissleder R, Lee H. Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy. Nat Med 2012; 18:1835-40. PubMed
  • Mizrak A, Bolukbasi MF, Ozdener GB, Brenner GJ, Madlener S, Erkan EP, Ströbel T, Breakefield XO, Saydam O. Genetically Engineered Microvesicles Carrying Suicide mRNA/Protein Inhibit Schwannoma Tumor Growth. Mol Ther 2012. PubMed
  • Maguire CA, Balaj L, Sivaraman S, Crommentuijn MH, Ericsson M, Mincheva-Nilsson L, Baranov V, Gianni D, Tannous BA, Sena-Esteves M, Breakefield XO, Skog J. Microvesicle-associated AAV Vector as a Novel Gene Delivery System. Mol Ther 2012. PubMed
  • Bolukbasi MF, Mizrak A, Ozdener GB, Madlener S, Ströbel T, Erkan EP, Fan JB, Breakefield XO, Saydam O. miR-1289 and "Zipcode"-like Sequence Enrich mRNAs in Microvesicles. Mol Ther Nucleic Acids 2013; 1:e10. PubMed
  • van der Vos KE, Balaj L, Skog J, Breakefield XO. Brain tumor microvesicles: insights into intercellular communication in the nervous system. Cell Mol Neurobiol 2011; 31:949-59. PubMed
  • Balaj L, Lessard R, Dai L, Cho YJ, Pomeroy SL, Breakefield XO, Skog J. Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2011; 2:180. PubMed
  • Saydam O, Senol O, Würdinger T, Mizrak A, Ozdener GB, Stemmer-Rachamimov AO, Yi M, Stephens RM, Krichevsky AM, Saydam N, Brenner GJ, Breakefield XO. miRNA-7 attenuation in Schwannoma tumors stimulates growth by upregulating three oncogenic signaling pathways. Cancer Res 2011; 71:852-61. PubMed
  • Saydam O, Shen Y, Würdinger T, Senol O, Boke E, James MF, Tannous BA, Stemmer-Rachamimov AO, Yi M, Stephens RM, Fraefel C, Gusella JF, Krichevsky AM, Breakefield XO. Downregulated microRNA-200a in meningiomas promotes tumor growth by reducing E-cadherin and activating the Wnt/beta-catenin signaling pathway. Mol Cell Biol 2009; 29:5923-40. PubMed
  • Skog J,Wurdinger T,van Rijn S,Meijer DH,Gainche L,Sena-Esteves M,Curry WT Jr,Carter BS,Krichevsky AM,Breakefield XO. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008; 10:1470-6. PubMed
  • Wurdinger T,Tannous BA,Saydam O,Skog J,Grau S,Soutschek J,Weissleder R,Breakefield XO,Krichevsky AM. miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell 2008; 14:382-93. PubMed
Hide