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

Photo of Xandra O. Breakefield, PhD

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


breakefield@hms.harvard.edu

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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 from Harvard Catalyst Profiles

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  • Mahjoum S, Rufino-Ramos D, Pereira de Almeida L, Broekman MLD, Breakefield XO, van Solinge TS. Living Proof of Activity of Extracellular Vesicles in the Central Nervous System. Int J Mol Sci 2021. PubMed
  • Nieland L, Morsett LM, Broekman MLD, Breakefield XO, Abels ER. Extracellular Vesicle-Mediated Bilateral Communication between Glioblastoma and Astrocytes. Trends Neurosci 2021; 44:215-226. PubMed
  • Cheah PS, Prabhakar S, Yellen D, Beauchamp RL, Zhang X, Kasamatsu S, Bronson RT, Thiele EA, Kwiatkowski DJ, Stemmer-Rachamimov A, György B, Ling KH, Kaneki M, Tannous BA, Ramesh V, Maguire CA, Breakefield XO. Gene therapy for tuberous sclerosis complex type 2 in a mouse model by delivery of AAV9 encoding a condensed form of tuberin. Sci Adv 2021. PubMed
  • Abels ER, Maas SLN, Tai E, Ting DT, Broekman MLD, Breakefield XO, El Khoury J. GlioM&M: Web-based tool for studying circulating and infiltrating monocytes and macrophages in glioma. Sci Rep 2020; 10:9898. PubMed
  • O'Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol 2020. PubMed
  • Maas SLN, Abels ER, Van De Haar LL, Zhang X, Morsett L, Sil S, Guedes J, Sen P, Prabhakar S, Hickman SE, Lai CP, Ting DT, Breakefield XO, Broekman MLD, El Khoury J. Glioblastoma hijacks microglial gene expression to support tumor growth. J Neuroinflammation 2020; 17:120. PubMed
  • Dusoswa SA, Verhoeff J, Abels E, Méndez-Huergo SP, Croci DO, Kuijper LH, de Miguel E, Wouters VMCJ, Best MG, Rodriguez E, Cornelissen LAM, van Vliet SJ, Wesseling P, Breakefield XO, Noske DP, Würdinger T, Broekman MLD, Rabinovich GA, van Kooyk Y, Garcia-Vallejo JJ. Glioblastomas exploit truncated Olinked glycans for local and distant immune modulation via the macrophage galactose-type lectin. Proc Natl Acad Sci U S A 2020; 117:3693-3703. PubMed
  • Lucero R, Zappulli V, Sammarco A, Murillo OD, Cheah PS, Srinivasan S, Tai E, Ting DT, Wei Z, Roth ME, Laurent LC, Krichevsky AM, Breakefield XO, Milosavljevic A. Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells. Cell Rep 2020; 30:2065-2074.e4. PubMed
  • van Solinge TS, Abels ER, van de Haar LL, Hanlon KS, Maas SLN, Schnoor R, de Vrij J, Breakefield XO, Broekman MLD. Versatile Role of Rab27a in Glioma: Effects on Release of Extracellular Vesicles, Cell Viability, and Tumor Progression. Front Mol Biosci 2020; 7:554649. PubMed
  • Chi AS, Cahill DP, Reardon DA, Wen PY, Mikkelsen T, Peereboom DM, Wong ET, Gerstner ER, Dietrich J, Plotkin SR, Norden AD, Lee EQ, Nayak L, Tanaka S, Wakimoto H, Lelic N, Koerner MV, Klofas LK, Bertalan MS, Arrillaga-Romany IC, Betensky RA, Curry WT, Borger DR, Balaj L, Kitchen RR, Chakrabortty SK, Valentino MD, Skog J, Breakefield XO, Iafrate AJ, Batchelor TT. Exploring Predictors of Response to Dacomitinib in -Amplified Recurrent Glioblastoma. JCO Precis Oncol 2020. PubMed
  • Yekula A, Minciacchi VR, Morello M, Shao H, Park Y, Zhang X, Muralidharan K, Freeman MR, Weissleder R, Lee H, Carter B, Breakefield XO, Di Vizio D, Balaj L. Large and small extracellular vesicles released by glioma cells and . J Extracell Vesicles 2020; 9:1689784. PubMed
  • Prabhakar S, Cheah PS, Zhang X, Zinter M, Gianatasio M, Hudry E, Bronson RT, Kwiatkowski DJ, Stemmer-Rachamimov A, Maguire CA, Sena-Esteves M, Tannous BA, Breakefield XO. Long-Term Therapeutic Efficacy of Intravenous AAV-Mediated Hamartin Replacement in Mouse Model of Tuberous Sclerosis Type 1. Mol Ther Methods Clin Dev 2019; 15:18-26. PubMed
  • Zaborowski MP, Cheah PS, Zhang X, Bushko I, Lee K, Sammarco A, Zappulli V, Maas SLN, Allen RM, Rumde P, György B, Aufiero M, Schweiger MW, Lai CP, Weissleder R, Lee H, Vickers KC, Tannous BA, Breakefield XO. Membrane-bound Gaussia luciferase as a tool to track shedding of membrane proteins from the surface of extracellular vesicles. Sci Rep 2019; 9:17387. PubMed
  • Hanlon KS, Kleinstiver BP, Garcia SP, Zaborowski MP, Volak A, Spirig SE, Muller A, Sousa AA, Tsai SQ, Bengtsson NE, Lööv C, Ingelsson M, Chamberlain JS, Corey DP, Aryee MJ, Joung JK, Breakefield XO, Maguire CA, György B. High levels of AAV vector integration into CRISPR-induced DNA breaks. Nat Commun 2019; 10:4439. PubMed
  • Abels ER, Maas SLN, Nieland L, Wei Z, Cheah PS, Tai E, Kolsteeg CJ, Dusoswa SA, Ting DT, Hickman S, El Khoury J, Krichevsky AM, Broekman MLD, Breakefield XO. Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21. Cell Rep 2019; 28:3105-3119.e7. PubMed
  • Abels ER, Broekman MLD, Breakefield XO, Maas SLN. Glioma EVs Contribute to Immune Privilege in the Brain. Trends Cancer 2019; 5:393-396. PubMed
  • Wiklander OPB, Brennan MÁ, Lötvall J, Breakefield XO, El Andaloussi S. Advances in therapeutic applications of extracellular vesicles. Sci Transl Med 2019. PubMed
  • Das S, , Ansel KM, Bitzer M, Breakefield XO, Charest A, Galas DJ, Gerstein MB, Gupta M, Milosavljevic A, McManus MT, Patel T, Raffai RL, Rozowsky J, Roth ME, Saugstad JA, Van Keuren-Jensen K, Weaver AM, Laurent LC. The Extracellular RNA Communication Consortium: Establishing Foundational Knowledge and Technologies for Extracellular RNA Research. Cell 2019; 177:231-242. PubMed
  • Srinivasan S, Yeri A, Cheah PS, Chung A, Danielson K, De Hoff P, Filant J, Laurent CD, Laurent LD, Magee R, Moeller C, Murthy VL, Nejad P, Paul A, Rigoutsos I, Rodosthenous R, Shah RV, Simonson B, To C, Wong D, Yan IK, Zhang X, Balaj L, Breakefield XO, Daaboul G, Gandhi R, Lapidus J, Londin E, Patel T, Raffai RL, Sood AK, Alexander RP, Das S, Laurent LC. Small RNA Sequencing across Diverse Biofluids Identifies Optimal Methods for exRNA Isolation. Cell 2019; 177:446-462.e16. PubMed
  • Zaborowski MP, Lee K, Na YJ, Sammarco A, Zhang X, Iwanicki M, Cheah PS, Lin HY, Zinter M, Chou CY, Fulci G, Tannous BA, Lai CP, Birrer MJ, Weissleder R, Lee H, Breakefield XO. Methods for Systematic Identification of Membrane Proteins for Specific Capture of Cancer-Derived Extracellular Vesicles. Cell Rep 2019; 27:255-268.e6. PubMed
  • Ricklefs FL, Maire CL, Reimer R, Dührsen L, Kolbe K, Holz M, Schneider E, Rissiek A, Babayan A, Hille C, Pantel K, Krasemann S, Glatzel M, Heiland DH, Flitsch J, Martens T, Schmidt NO, Peine S, Breakefield XO, Lawler S, Chiocca EA, Fehse B, Giebel B, Görgens A, Westphal M, Lamszus K. Imaging flow cytometry facilitates multiparametric characterization of extracellular vesicles in malignant brain tumours. J Extracell Vesicles 2019; 8:1588555. PubMed
  • Fraser K, Jo A, Giedt J, Vinegoni C, Yang KS, Peruzzi P, Chiocca EA, Breakefield XO, Lee H, Weissleder R. Characterization of single microvesicles in plasma from glioblastoma patients. 2018. PubMed
  • Broekman ML, Maas SLN, Abels ER, Mempel TR, Krichevsky AM, Breakefield XO. Multidimensional communication in the microenvirons of glioblastoma. Nat Rev Neurol 2018; 14:482-495. PubMed
  • Ricklefs FL, Alayo Q, Krenzlin H, Mahmoud AB, Speranza MC, Nakashima H, Hayes JL, Lee K, Balaj L, Passaro C, Rooj AK, Krasemann S, Carter BS, Chen CC, Steed T, Treiber J, Rodig S, Yang K, Nakano I, Lee H, Weissleder R, Breakefield XO, Godlewski J, Westphal M, Lamszus K, Freeman GJ, Bronisz A, Lawler SE, Chiocca EA. Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci Adv 2018; 4:eaar2766. PubMed
  • Lee K, Fraser K, Ghaddar B, Yang K, Kim E, Balaj L, Chiocca EA, Breakefield XO, Lee H, Weissleder R. Multiplexed Profiling of Single Extracellular Vesicles. ACS Nano 2018. PubMed
  • Wei Z, Batagov AO, Schinelli S, Wang J, Wang Y, El Fatimy R, Rabinovsky R, Balaj L, Chen CC, Hochberg F, Carter B, Breakefield XO, Krichevsky AM. Coding and noncoding landscape of extracellular RNA released by human glioma stem cells. Nat Commun 2017; 8:1145. PubMed
  • Figueroa JM, Skog J, Akers J, Li H, Komotar R, Jensen R, Ringel F, Yang I, Kalkanis S, Thompson R, LoGuidice L, Berghoff E, Parsa A, Liau L, Curry W, Cahill D, Bettegowda C, Lang FF, Chiocca EA, Henson J, Kim R, Breakefield X, Chen C, Messer K, Hochberg F, Carter BS. Detection of wild-type EGFR amplification and EGFRvIII mutation in CSF-derived extracellular vesicles of glioblastoma patients. 2017; 19:1494-1502. PubMed
  • Speranza MC, Passaro C, Ricklefs F, Kasai K, Klein SR, Nakashima H, Kaufmann JK, Ahmed AK, Nowicki MO, Obi P, Bronisz A, Aguilar-Cordova E, Aguilar LK, Guzik BW, Breakefield X, Weissleder R, Freeman GJ, Reardon DA, Wen P, Chiocca EA, Lawler SE. Preclinical investigation of gene-mediated cytotoxic immunotherapy and checkpoint blockade in glioblastoma. 2017. PubMed
  • György B, Sage C, Indzhykulian AA, Scheffer DI, Brisson AR, Tan S, Wu X, Volak A, Mu D, Tamvakologos PI, Li Y, Fitzpatrick Z, Ericsson M, Breakefield XO, Corey DP, Maguire CA. Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV. Mol Ther 2017; 25:379-391. PubMed
  • Soares VY, Atai NA, Fujita T, Dilwali S, Sivaraman S, Landegger LD, Hochberg FH, Oliveira CA, Bahmad F, Breakefield XO, Stankovic KM. Extracellular vesicles derived from human vestibular schwannomas associated with poor hearing damage cochlear cells. 2016. PubMed
  • Abels ER, Breakefield XO. Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cell Mol Neurobiol 2016. PubMed
  • Hall J, Prabhakar S, Balaj L, Lai CP, Cerione RA, Breakefield XO. Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson's Disease, Glioma, and Schwannoma. Cell Mol Neurobiol 2016. PubMed
  • Ricklefs F, Mineo M, Rooj AK, Nakano I, Charest A, Weissleder R, Breakefield XO, Chiocca EA, Godlewski J, Bronisz A. Extracellular vesicles from high grade glioma exchange diverse pro-oncogenic signals that maintain intratumoral heterogeneity. Cancer Res 2016. PubMed
  • Pucci F, Garris C, Lai CP, Newton A, Pfirschke C, Engblom C, Alvarez D, Sprachman M, Evavold C, Magnuson A, von Andrian UH, Glatz K, Breakefield XO, Mempel TR, Weissleder R, Pittet MJ. SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions. Science 2016. PubMed
  • van der Vos KE, Abels ER, Zhang X, Lai C, Carrizosa E, Oakley D, Prabhakar S, Mardini O, Crommentuijn MH, Skog J, Krichevsky AM, Stemmer-Rachamimov A, Mempel TR, El Khoury J, Hickman SE, Breakefield XO. Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain. 2016; 18:58-69. PubMed
  • Prabhakar S, Zhang X, Goto J, Han S, Lai C, Bronson R, Sena-Esteves M, Ramesh V, Stemmer-Rachamimov A, Kwiatkowski DJ, Breakefield XO. Survival benefit and phenotypic improvement by hamartin gene therapy in a tuberous sclerosis mouse brain model. Neurobiol Dis 2015; 82:22-31. PubMed
  • 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
  • Shao H, Chung J, Lee K, Balaj L, Min C, Carter BS, Hochberg FH, Breakefield XO, Lee H, Weissleder R. Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma. Nat Commun 2015; 6:6999. PubMed
  • Lai CP, Kim EY, Badr CE, Weissleder R, Mempel TR, Tannous BA, Breakefield XO. Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters. Nat Commun 2015; 6:7029. PubMed
  • Balaj L, Atai NA, Chen W, Mu D, Tannous BA, Breakefield XO, Skog J, Maguire CA. Heparin affinity purification of extracellular vesicles. Sci Rep 2015; 5:10266. PubMed
  • György B, Hung ME, Breakefield XO, Leonard JN. Therapeutic applications of extracellular vesicles: clinical promise and open questions. Annu Rev Pharmacol Toxicol 2015. PubMed
  • Plotkin SR, Albers AC, Babovic-Vuksanovic D, Blakeley JO, Breakefield XO, Dunn CM, Evans DG, Fisher MJ, Friedman JM, Giovannini M, Gutmann DH, Kalamarides M, McClatchey AI, Messiaen L, Morrison H, Parkinson DB, Stemmer-Rachamimov AO, Van Raamsdonk CD, Riccardi VM, Rosser T, Schindeler A, Smith MJ, Stevenson DA, Ullrich NJ, van der Vaart T, Weiss B, Widemann BC, Zhu Y, Bakker AC, Lloyd AC. Update from the 2013 International Neurofibromatosis Conference. Am J Med Genet A 2014. PubMed
  • Maguire CA, Ramirez SH, Merkel SF, Sena-Esteves M, Breakefield XO. Gene therapy for the nervous system: challenges and new strategies. 2014; 11:817-39. 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 2014; 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
  • 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 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
  • 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 2012; 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
  • 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
  • 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, 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
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DF/HCC members that share similar concepts* with Xandra O. Breakefield, PhD but have yet to coauthor a publication with this researcher.

* Concepts are MeSH terms, automatically derived from member publications

Similar Members