Xandra O. Breakefield

Research Investigator Profile

Xandra O. Breakefield, PhD

  • Professor of Neurology,
    Harvard Medical School
  • Geneticist, Neurology and Radiology, Massachusetts General Hospital



Research Description

Molecular genetic and imaging methods are used to gain insight into the molecular etiology of torsion dystonia and to develop strategies for brain tumor therapy.

Torsion dystonia is a movement disorder characterized by contracted postures due to abnormal sensori-motor communication. The protein, torsinA responsible for most early onset cases is a AAA+ protein localized in the endoplasmic reticulum (ER) and nuclear envelope (NE). TorsinA is expressed at highest levels in the perinatal period in neurons and appears to be involved in protein secretion and linking the NE/ER to the cytoskeleton. Current studies (Dr. Nery) focus on understanding the role of torsinA in neuronal migration using time lapse confocal microscopy. Parallel efforts (Dr. Bragg) use high throughput screening methods to identify drug candidates which can normalize functions in cells expressing mutant torsinA.

Research on brain tumors uses HSV, AAV and lentivirus vectors to deliver therapeutic genes and imaging reporters in mouse models of glioblastoma, as well as meningioma and schwannoma tumors associated with neurofibromatosis type 2 and cortical overgrowths associated with tuberous sclerosis. The current focus is on understanding how microRNA regulate tumor growth (Drs. Saydam & Wurdinger) and how tumors modify their environment through release of microvesicles (Dr. Skog).

To learn more, visit the Breakefield Lab.

Research interests Neurogenetics, neurologic disease, brain tumors, viral vectors, microRNAs, gene therapy, exosomes, dystonia, neuronal migration
Research techniques Genetics, molecular biology, cell biology, immunocytochemistry, western blots/immune precipitation, transgenic and knock-out mouse models, tumor xenograft models, in vivo imaging, high throughput drug screening
Diseases studied Torsion dystonia, NF2-related meningioma and schwannoma, glioblastoms, tuberous sclerosis
Selected publications
  1. Wurdinger, T., Badr, C., Pike, L., de Kleine, R., Weissleder, R., Breakefield, X.O., Tannous, B.A.: A secreted luciferase for ex vivo monitoring of in vivo processes. Nature Methods, in press.
  2. Breakefield, X.O., Blood, A.J., Li, Y., Hallett, M., Hanson, P.I., Standaert, D.G.: The pathophysiologic basis of the dystonias. Nature Reviews Neuroscience, in press.
  3. Hewett, J.W., Tannous, B., Niland, B.P., Nery, F.C., Zeng, J., Li, Y., Breakefield, X.O.: Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells.  Proc. Natl. Acad. Sci. U S A 104: 7271-7276, 2007.
  4. Tannous, B.A., Grimm, J., Perry, K.F., Chen, J.W., Weisselder, R., and Breakefield, X.O.:  Metabolic biotinylation of cell surface receptors for in vivo imaging.  Nature Methods, 3:391-396, 2006.
  5. Shah, K., Bureau, E., Kim, D.E. Yang, K., Tang, Y., Weissleder, R., Breakefield, X.O.:  Glioma therapy and real-time imaging of neural precursor cell migration and tumor regression.  Annals Neurol. 57: 34-41, 2005.
NCBI PubMed link NCBI PubMed publications
E-mail address breakefield@hms.harvard.edu
Lab mailing address Massachusetts General Hospital, Neurology
CNY Building 149, Room 6203
149 13th Street
Charlestown, MA 02129


Updated 03/05/2012

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