Rosalind A. Segal, MD, PhD

Rosalind A. Segal, MD, PhD

Pediatric Hematology/Oncology

Contact Information

Office Phone Number





Rosalind A. Segal, MD, PhD

Dr. Segal received her PhD in 1985 from Rockefeller University and her MD in 1986 from Cornell University Medical College, followed by a residency in the Harvard Neurology Program. As a postdoctoral fellow at Massachusetts Institute of Technology, she investigated the role of nerve growth factors in regulating cerebellar development and tumor formation. She joined DFCI in 1998, where she is principally involved in laboratory research on nervous system development.



Edward J. Benz Jr., MD, Chair
Professor of Neurobiology, Harvard Medical School

Clinical Interests

Brain tumors, Pediatric brain tumors

Recent Awards

  • National Merit Scholarship 1975
  • National Science Foundation Pre-doctoral Fellowship 1979
  • Phi Beta Kappa, Harvard College 1979
  • Summa Cum Laude, Harvard University 1979
  • Medical Science Training Program Pre-doctoral Fellowship 1980
  • Dana Foundation Postdoctoral Fellowship 1990
  • Robert Ebert Clinical Scholar Klingenstein Award 1996
  • Claudia Adams Barr Investigator, Barr Foundation 1998
  • Pediatric Brain Tumor Foundation Award 2001
  • McDonnell Foundation Award 2001
  • NIH Director's Pioneer Award 2006
  • Ted Williams Senior Investigator, Dana-Farber Cancer Institute 2009
  • American Association of Physicians



    Growth Factors in Central Nervous System Development and Oncogenesis

    Our lab is interested in mechanisms whereby extracellular stimuli regulate proliferation and survival in the developing nervous system.

    Neurotrophin Signaling

    In order for target-derived neurotrophins to regulate the survival of a developing presynaptic cell, a signal must be propagated from the nerve terminal along the axon to the nucleus. We found that activated Trk receptors function as rapid retrograde signal carriers to elicit nuclear responses to target derived neurotrophins. Our data indicate that the mechanism of signal propagation is retrograde vesicular transport of activated Trk-ligand complexes. Once they reach the cell body, activated receptors elicit nuclear responses-including phosphorylation of the transcription factor CREB and subsequent induction of the immediate early gene c-fos.

    We are currently studying other intermediates required for retrograde signaling and the potential differences in the biological responses to retrograde or local stimulation with growth factors.

    Neurotrophins & Cancer

    While our studies have highlighted the role of BDNF in normal cerebellar development, we have also demonstrated that neurotrophins, in particular NT3, have a role in cerebellar diseases.

    Unregulated growth of cerebellar granule neuronal precursors results in formation of a tumor, known as medulloblastoma. We have found the NT3 receptor TrkC is expressed in these tumors, and that the level of expression is a prognostic indicator for clinical progression. Furthermore, our data show that NT3 induces an apoptotic response in medulloblastoma tumor cells, indicating that neurotrophins have potential application in tumor therapy.

    Cerebellar Development

    While target derived neurotrophins are required for the survival of developing neurons in the peripheral nervous system, the functions of neurotrophins in the central nervous system have been unclear. Mice with a targeted gene deletion of brain-derived neurotrophic factor (BDNF) exhibit a wide based gait, and a defect in cerebellar foliation pattern. At the cellular level cerebellar granule cell survival and migration are both impaired in mutant animals. However, there is an increase in granule cell proliferation in mutants. These data suggest that BDNF acts as an autocrine/paracrine factor to regulate survival, migration, and differentiation of developing CNS neurons, and thereby affects neural patterning.


      • TMEM161B regulates cerebral cortical gyration, Sonic Hedgehog signaling, and ciliary structure in the developing central nervous system. Proc Natl Acad Sci U S A. 2023 Jan 24; 120(4):e2209964120. View in: Pubmed

      • An affinity for brainstem microglia in pediatric high-grade gliomas of brainstem origin. Neurooncol Adv. 2022 Jan-Dec; 4(1):vdac117. View in: Pubmed

      • Synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas. Neurooncol Adv. 2022 Jan-Dec; 4(1):vdac049. View in: Pubmed

      • Sarm1 activation produces cADPR to increase intra-axonal Ca++ and promote axon degeneration in PIPN. J Cell Biol. 2022 02 07; 221(2). View in: Pubmed

      • Diversity of developing peripheral glia revealed by single-cell RNA sequencing. Dev Cell. 2021 09 13; 56(17):2516-2535.e8. View in: Pubmed

      • Uncomfortably numb: how Nav1.7 mediates paclitaxel-induced peripheral neuropathy. Brain. 2021 07 28; 144(6):1621-1623. View in: Pubmed

      • The Eya1 Phosphatase Mediates Shh-Driven Symmetric Cell Division of Cerebellar Granule Cell Precursors. Dev Neurosci. 2020; 42(5-6):170-186. View in: Pubmed

      • Binding and transport of SFPQ-RNA granules by KIF5A/KLC1 motors promotes axon survival. J Cell Biol. 2021 01 04; 220(1). View in: Pubmed

      • Understanding the epigenetic landscape and cellular architecture of childhood brain tumors. Neurochem Int. 2021 03; 144:104940. View in: Pubmed

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      • How neuronal activity regulates glioma cell proliferation. Neuro Oncol. 2015 Dec; 17(12):1543-4. View in: Pubmed

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      • Expression profiles of 151 pediatric low-grade gliomas reveal molecular differences associated with location and histological subtype. Neuro Oncol. 2015 Nov; 17(11):1486-96. View in: Pubmed

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      • Shh-proteoglycan interactions regulate maturation of olfactory glomerular circuitry. Dev Neurobiol. 2014 Dec; 74(12):1255-67. View in: Pubmed

      • Pediatric low-grade gliomas: how modern biology reshapes the clinical field. Biochim Biophys Acta. 2014 Apr; 1845(2):294-307. View in: Pubmed

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      • Coordinate activation of Shh and PI3K signaling in PTEN-deficient glioblastoma: new therapeutic opportunities. Nat Med. 2013 Nov; 19(11):1518-23. View in: Pubmed

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      • Target-derived neurotrophins coordinate transcription and transport of bclw to prevent axonal degeneration. J Neurosci. 2013 Mar 20; 33(12):5195-207. View in: Pubmed

      • Avanafil for the treatment of erectile dysfunction. Drugs Today (Barc). 2012 Jan; 48(1):7-15. View in: Pubmed

      • From synapse to nucleus and back again--communication over distance within neurons. J Neurosci. 2011 Nov 09; 31(45):16045-8. View in: Pubmed

      • Randomized trial of a lifestyle intervention for women with early-stage breast cancer (BC) receiving adjuvant hormone therapy: Initial results. J Clin Oncol. 2011 May 20; 29(15_suppl):512. View in: Pubmed

      • Numb links extracellular cues to intracellular polarity machinery to promote chemotaxis. Dev Cell. 2011 May 17; 20(5):610-22. View in: Pubmed

      • Neuromuscular junction defects in mice with mutation of dynein heavy chain 1. PLoS One. 2011 Feb 04; 6(2):e16753. View in: Pubmed

      • Sensory neuropathy attributable to loss of Bcl-w. J Neurosci. 2011 Feb 02; 31(5):1624-34. View in: Pubmed

      • The longer U(T)R, the further you go. Nat Neurosci. 2010 Mar; 13(3):273-5. View in: Pubmed

      • Live or let die: CCM2 provides the link. Neuron. 2009 Sep 10; 63(5):559-60. View in: Pubmed

      • A retrograde neuronal survival response: target-derived neurotrophins regulate MEF2D and bcl-w. J Neurosci. 2009 May 20; 29(20):6700-9. View in: Pubmed

      • Anterograde transport of TrkB in axons is mediated by direct interaction with Slp1 and Rab27. Dev Cell. 2009 May; 16(5):675-86. View in: Pubmed

      • Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses. Nat Neurosci. 2009 Apr; 12(4):409-17. View in: Pubmed

      • Olfactory behavioral testing in the adult mouse. J Vis Exp. 2009 Jan 28; (23). View in: Pubmed

      • Proteoglycan interactions with Sonic Hedgehog are selectively required for mitogenic responses. Nature Neuroscience. 2009; revised ms submitted. View in: Pubmed

      • Preparation and maintenance of dorsal root ganglia neurons in compartmented cultures. J Vis Exp. 2008 Oct 17; (20). View in: Pubmed

      • A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes. J Cell Biol. 2008 Jun 16; 181(6):1027-39. View in: Pubmed

      • Action in the axon: generation and transport of signaling endosomes. Curr Opin Neurobiol. 2008 Jun; 18(3):270-5. View in: Pubmed

      • Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors. Neuron. 2007 Jul 05; 55(1):53-68. View in: Pubmed

      • CXCR4 inhibition synergizes with cytotoxic chemotherapy in gliomas. Clin Cancer Res. 2006 Nov 15; 12(22):6765-71. View in: Pubmed

      • Changing demographics of locally advanced breast cancer: Data from a regional cancer centre. J Clin Oncol. 2006 Jun 20; 24(18_suppl):10780. View in: Pubmed

      • Phase II study of neoadjuvant docetaxel and androgen suppression (AS) plus radiation therapy (RT) for high-risk localized prostate cancer (HRLCaP). J Clin Oncol. 2006 Jun 20; 24(18_suppl):4631. View in: Pubmed

      • Migration from a mitogenic niche promotes cell-cycle exit. J Neurosci. 2005 Nov 09; 25(45):10437-45. View in: Pubmed

      • Subtracting the Math: prominin-positive cerebellar stem cells in white matter. Nat Neurosci. 2005 Jun; 8(6):699-701. View in: Pubmed

      • Dynein motors transport activated Trks to promote survival of target-dependent neurons. Nat Neurosci. 2004 Jun; 7(6):596-604. View in: Pubmed

      • Medulloblastoma tumorigenesis diverges from cerebellar granule cell differentiation in patched heterozygous mice. Dev Biol. 2003 Nov 01; 263(1):50-66. View in: Pubmed

      • A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci U S A. 2003 Nov 11; 100(23):13513-8. View in: Pubmed

      • Selectivity in neurotrophin signaling: theme and variations. Annu Rev Neurosci. 2003; 26:299-330. View in: Pubmed

      • Modulation of autoreactive responses of peripheral blood lymphocytes of patients with systemic lupus erythematosus by peptides based on human and murine anti-DNA autoantibodies. Clin Exp Immunol. 2003 Feb; 131(2):385-92. View in: Pubmed

      • Regional expression of p75NTR contributes to neurotrophin regulation of cerebellar patterning. Mol Cell Neurosci. 2003 Jan; 22(1):1-13. View in: Pubmed

      • Growth, survival and migration: the Trk to cancer. Cancer Treat Res. 2003; 115:1-18. View in: Pubmed

      • P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature. 2002 Nov 07; 420(6911):74-8. View in: Pubmed

      • Medulloblastomas and primitive neuroectodermal tumors rarely contain polyomavirus DNA sequences. Neuro Oncol. 2002 07; 4(3):165-70. View in: Pubmed

      • High-resolution imaging demonstrates dynein-based vesicular transport of activated Trk receptors. J Neurobiol. 2002 Jun 15; 51(4):302-12. View in: Pubmed

      • Retrograde neurotrophin signaling: Trk-ing along the axon. Curr Opin Neurobiol. 2002 Jun; 12(3):268-74. View in: Pubmed

      • Cerebellar proteoglycans regulate sonic hedgehog responses during development. Development. 2002 May; 129(9):2223-32. View in: Pubmed

      • Location, location, location: a spatial view of neurotrophin signal transduction. Trends Neurosci. 2002 Mar; 25(3):160-5. View in: Pubmed

      • BDNF stimulates migration of cerebellar granule cells. Development. 2002 Mar; 129(6):1435-42. View in: Pubmed

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      • SDF-1 alpha induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells. Development. 2001 Jun; 128(11):1971-81. View in: Pubmed

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      • Sustained signaling by phospholipase C-gamma mediates nerve growth factor-triggered gene expression. Mol Cell Biol. 2001 Apr; 21(8):2695-705. View in: Pubmed

      • Rett syndrome model suggests MECP2 gives neurons the quiet they need to think. Nat Neurosci. 2001 Apr; 4(4):342-3. View in: Pubmed

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      • Surveillance programs for early stage non-seminomatous testicular cancer: a practice guideline. Can J Urol. 2001 Feb; 8(1):1184-92. View in: Pubmed

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      • Suppression of experimental systemic lupus erythematosus (SLE) in mice via TNF inhibition by an anti-TNFalpha monoclonal antibody and by pentoxiphylline. Lupus. 2001; 10(1):23-31. View in: Pubmed

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      • Cell surface Trk receptors mediate NGF-induced survival while internalized receptors regulate NGF-induced differentiation. J Neurosci. 2000 Aug 01; 20(15):5671-8. View in: Pubmed

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      • Effect of aging on cytokine production in normal and experimental systemic lupus erythematosus-afflicted mice. Exp Gerontol. 2000 Mar; 35(2):225-36. View in: Pubmed

      • Combination of epirubicin and cisplatin in hormone-refractory metastatic prostate cancer. Am J Clin Oncol. 1999 Oct; 22(5):471-4. View in: Pubmed

      • Rapid nuclear responses to target-derived neurotrophins require retrograde transport of ligand-receptor complex. J Neurosci. 1999 Sep 15; 19(18):7889-900. View in: Pubmed

      • TrkA glycosylation regulates receptor localization and activity. J Neurobiol. 1999 May; 39(2):323-36. View in: Pubmed

      • Intermittent androgen suppression in the management of prostate cancer. Urology. 1999 Mar; 53(3):530-4. View in: Pubmed

      • Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas. Cancer Res. 1999 Feb 01; 59(3):711-9. View in: Pubmed

      • Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci U S A. 1998 Aug 04; 95(16):9448-53. View in: Pubmed

      • Cerebellar pathology in BDNF -/- mice: the classic view of neurotrophins is changing. Mol Psychiatry. 1998 Mar; 3(2):116-20. View in: Pubmed

      • Neurotrophins in cerebellar granule cell development and medulloblastoma. J Neurooncol. 1997 Dec; 35(3):347-52. View in: Pubmed

      • Trk receptors function as rapid retrograde signal carriers in the adult nervous system. J Neurosci. 1997 Sep 15; 17(18):7007-16. View in: Pubmed

      • Abnormal cerebellar development and foliation in BDNF-/- mice reveals a role for neurotrophins in CNS patterning. Neuron. 1997 Aug; 19(2):269-81. View in: Pubmed

      • Blockade of endogenous ligands of trkB inhibits formation of ocular dominance columns. Neuron. 1997 Jul; 19(1):63-76. View in: Pubmed

      • Effect of aging on cytokine production in normal and experimental systemic lupus erythematosus afflicted mice. Mech Ageing Dev. 1997 Jun; 96(1-3):47-58. View in: Pubmed

      • Cytokine manipulation by methotrexate treatment in murine experimental systemic lupus erythematosus. J Rheumatol. 1997 Jun; 24(6):1075-82. View in: Pubmed

      • Kinetics of cytokine production in experimental systemic lupus erythematosus: involvement of T helper cell 1/T helper cell 2-type cytokines in disease. J Immunol. 1997 Mar 15; 158(6):3009-16. View in: Pubmed

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      • Neurotrophins and programmed cell death during cerebellar development. Adv Neurol. 1997; 72:79-86. View in: Pubmed

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      Dana-Farber Cancer Institute

      Location Avtar

      Dana-Farber Cancer Institute

      450 Brookline Avenue Smith 1058A Boston, MA 02215
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