Photo of Rosalind A. Segal,  MD, PhD

Rosalind A. Segal, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4737
Fax: (617) 632-2085

Rosalind A. Segal, MD, PhD

Dana-Farber Cancer Institute


  • Professor, Neurobiology, Harvard Medical School
  • Professor of Neurobiology, Ted Williams Senior Investigator, Cancer Biology and Pediatric Oncology, Dana-Farber Cancer Institute
  • Co-Chair, Cancer Biology, Dana-Farber Cancer Institute
  • Edward J. Benz Jr., MD, Chair, Dana-Farber Cancer Institute


Research Abstract

The research work in our laboratory has focused on growth factor signaling pathways that regulate survival, proliferation and migration in the developing nervous system. These pathways are normally exquisitely regulated; disruption of these pathways can result in brain tumors or neurodegenerative disorders.

Survival. During development, target derived neurotrophins promote the survival of presynapic cells, allowing neurons that are connected within a neural circuit to survive. Our studies investigate this long distance signaling. Our studies have identified a specialized gene expression program, the retrograde response genes, that prevent axonal degeneration. We use molecular imaging approacher to determine how transcripting and local ...of retrograde response genes are regulated.

Proliferation and migration. We have found that factors that contribute to the proliferation and migration of neural precursors in the developing brain also are responsible for the abnormal proliferation and migration of brain tumor cells. We have identified mechanisms whereby heparan sulgate proteoglycans and chemokines modulate SHH signaling and contribute to proliferation. Our studies focus on how these processes are regulated in normal development, and how this regulation is lost in cancers.


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  • Alencastro Veiga Cruzeiro G, Rota C, Hack OA, Segal R, Filbin MG. Understanding the epigenetic landscape and cellular architecture of childhood brain tumors. Neurochem. Int. 2021; 144:104940. PubMed
  • Merk DJ, Zhou P, Cohen SM, Pazyra-Murphy MF, Hwang GH, Rehm KJ, Alfaro J, Reid CM, Zhao X, Park E, Xu PX, Chan JA, Eck MJ, Nazemi KJ, Harwell CC, Segal RA. The Eya1 Phosphatase Mediates Shh-Driven Symmetric Cell Division of Cerebellar Granule Cell Precursors. Dev Neurosci 2021. PubMed
  • Monje M, Borniger JC, D'Silva NJ, Deneen B, Dirks PB, Fattahi F, Frenette PS, Garzia L, Gutmann DH, Hanahan D, Hervey-Jumper SL, Hondermarck H, Hurov JB, Kepecs A, Knox SM, Lloyd AC, Magnon C, Saloman JL, Segal RA, Sloan EK, Sun X, Taylor MD, Tracey KJ, Trotman LC, Tuveson DA, Wang TC, White RA, Winkler F. Roadmap for the Emerging Field of Cancer Neuroscience. Cell 2020; 181:219-222. PubMed
  • Staff NP, Fehrenbacher JC, Caillaud M, Damaj MI, Segal RA, Rieger S. Pathogenesis of paclitaxel-induced peripheral neuropathy: A current review of in vitro and in vivo findings using rodent and human model systems. Exp Neurol 2019; 324:113121. PubMed
  • Pak E, MacKenzie EL, Zhao X, Pazyra-Murphy MF, Park PMC, Wu L, Shaw DL, Addleson EC, Cayer SS, Lopez BG, Agar NYR, Rubin LL, Qi J, Merk DJ, Segal RA. A large-scale drug screen identifies selective inhibitors of class I HDACs as a potential therapeutic option for SHH medulloblastoma. 2019. PubMed
  • Dorsey SG, Kleckner IR, Barton D, Mustian K, O'Mara A, St Germain D, Cavaletti G, Danhauer SC, Hershman D, Hohmann AG, Hoke A, Hopkins JO, Kelly KP, Loprinzi CL, McLeod HL, Mohile S, Paice J, Rowland JH, Salvemini D, Segal RA, Lavoie Smith E, McCaskill Stevens W, Janelsins MC. NCI Clinical Trials Planning Meeting for prevention and treatment of chemotherapy-induced peripheral neuropathy. Journal of the National Cancer Institute 2019. PubMed
  • Merk DJ, Segal RA. Sonic Hedgehog Signaling is Blue: Insights from the Patched Mutant Mice. Trends Neurosci 2018; 41:870-872. PubMed
  • Pease-Raissi SE, Pazyra-Murphy MF, Li Y, Wachter F, Fukuda Y, Fenstermacher SJ, Barclay LA, Bird GH, Walensky LD, Segal RA. Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration. Neuron 2017; 96:373-386.e6. PubMed
  • Zhao X, Pak E, Ornell KJ, Pazyra-Murphy MF, MacKenzie EL, Chadwick EJ, Ponomaryov T, Kelleher JF, Segal RA. A transposon screen identifies loss of primary cilia as a mechanism of resistance to Smo inhibitors. 2017. PubMed
  • Ni J, Xie S, Ramkissoon SH, Luu V, Sun Y, Bandopadhayay P, Beroukhim R, Roberts TM, Stiles CD, Segal RA, Ligon KL, Hahn WC, Zhao JJ. Tyrosine receptor kinase B is a drug target in astrocytomas. 2016. PubMed
  • Sun Y, Alberta JA, Pilarz C, Calligaris D, Chadwick EJ, Ramkissoon SH, Ramkissoon LA, Garcia VM, Mazzola E, Goumnerova L, Kane M, Yao Z, Kieran MW, Ligon KL, Hahn WC, Garraway LA, Rosen N, Gray NS, Agar NY, Buhrlage SJ, Segal RA, Stiles CD. A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas. 2017. PubMed
  • Fukuda Y, Li Y, Segal RA. A Mechanistic Understanding of Axon Degeneration in Chemotherapy-Induced Peripheral Neuropathy. Front Neurosci 2017; 11:481. PubMed
  • Cosker KE, Fenstermacher SJ, Pazyra-Murphy MF, Elliott HL, Segal RA. The RNA-binding protein SFPQ orchestrates an RNA regulon to promote axon viability. Nat Neurosci 2016; 19:690-6. PubMed
  • Filbin MG, Segal RA. How neuronal activity regulates glioma cell proliferation. 2015. PubMed
  • Balastik M, Zhou XZ, Alberich-Jorda M, Weissova R, Žiak J, Pazyra-Murphy MF, Cosker KE, Machonova O, Kozmikova I, Chen CH, Pastorino L, Asara JM, Cole A, Sutherland C, Segal RA, Lu KP. Prolyl Isomerase Pin1 Regulates Axon Guidance by Stabilizing CRMP2A Selectively in Distal Axons. Cell Rep 2015; 13:812-28. PubMed
  • Zhao X, Segal RA. A Polyamine Twist on Hedgehog Signaling. Dev Cell 2015; 35:1-2. PubMed
  • Zhao X, Ponomaryov T, Ornell KJ, Zhou P, Dabral SK, Pak E, Li W, Atwood SX, Whitson RJ, Chang AL, Li J, Oro AE, Chan JA, Kelleher JF, Segal RA. RAS/MAPK Activation Drives Resistance to Smo Inhibition, Metastasis, and Tumor Evolution in Shh Pathway-Dependent Tumors. Cancer Res 2015. PubMed
  • Eisner A, Pazyra-Murphy MF, Durresi E, Zhou P, Zhao X, Chadwick EC, Xu PX, Hillman RT, Scott MP, Greenberg ME, Segal RA. The Eya1 phosphatase promotes Shh signaling during hindbrain development and oncogenesis. Dev Cell 2015; 33:22-35. PubMed
  • Chadwick EJ, Yang DP, Filbin MG, Mazzola E, Sun Y, Behar O, Pazyra-Murphy MF, Goumnerova L, Ligon KL, Stiles CD, Segal RA. A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies. 2015. PubMed
  • Persson L, Witt RM, Galligan M, Greer PL, Eisner A, Pazyra-Murphy MF, Datta SR, Segal RA. Shh-proteoglycan interactions regulate maturation of olfactory glomerular circuitry. Dev Neurobiol 2014. PubMed
  • Bergthold G, Bandopadhayay P, Bi WL, Ramkissoon L, Stiles C, Segal RA, Beroukhim R, Ligon KL, Grill J, Kieran MW. Pediatric low-grade gliomas: how modern biology reshapes the clinical field. Biochim Biophys Acta 2014; 1845:294-307. PubMed
  • Cosker KE, Segal RA. Neuronal signaling through endocytosis. Cold Spring Harb Perspect Biol 2014. PubMed
  • Filbin MG, Dabral SK, Pazyra-Murphy MF, Ramkissoon S, Kung AL, Pak E, Chung J, Theisen MA, Sun Y, Franchetti Y, Sun Y, Shulman DS, Redjal N, Tabak B, Beroukhim R, Wang Q, Zhao J, Dorsch M, Buonamici S, Ligon KL, Kelleher JF, Segal RA. Coordinate activation of Shh and PI3K signaling in PTEN-deficient glioblastoma: new therapeutic opportunities. Nat Med 2013; 19:1518-23. PubMed
  • Witt RM, Hecht ML, Pazyra-Murphy MF, Cohen SM, Noti C, van Kuppevelt TH, Fuller M, Chan JA, Hopwood JJ, Seeberger PH, Segal RA. Heparan sulfate proteoglycans containing a glypican 5 core and 2-O-sulfo-iduronic acid function as Sonic Hedgehog co-receptors to promote proliferation. J Biol Chem 2013; 288:26275-88. PubMed
  • Cosker KE, Pazyra-Murphy MF, Fenstermacher SJ, Segal RA. Target-derived neurotrophins coordinate transcription and transport of bclw to prevent axonal degeneration. J Neurosci 2013; 33:5195-207. PubMed
  • Courchesne SL, Karch C, Pazyra-Murphy MF, Segal RA. Sensory neuropathy attributable to loss of Bcl-w. J Neurosci 2011; 31:1624-34. PubMed
  • Courchesne SL, Pazyra-Murphy MF, Lee DJ, Segal RA. Neuromuscular junction defects in mice with mutation of dynein heavy chain 1. PLoS ONE 2011; 6:e16753. PubMed
  • Cosker KE, Segal RA. The longer U(T)R, the further you go. Nat Neurosci 2010; 13:273-5. PubMed
  • Gruber-Olipitz M, Segal RA. Live or let die: CCM2 provides the link. Neuron 2009; 63:559-60. PubMed
  • Pazyra-Murphy MF,Hans A,Courchesne SL,Karch C,Cosker KE,Heerssen HM,Watson FL,Kim T,Greenberg ME,Segal RA. A retrograde neuronal survival response: target-derived neurotrophins regulate MEF2D and bcl-w. J Neurosci 2009; 29:6700-9. PubMed
  • Arimura N,Kimura T,Nakamuta S,Taya S,Funahashi Y,Hattori A,Shimada A,Menager C,Kawabata S,Fujii K,Iwamatsu A,Segal RA,Fukuda M,Kaibuchi K. Anterograde transport of TrkB in axons is mediated by direct interaction with Slp1 and Rab27. Dev Cell 2009; 16:675-86. PubMed
  • Chan JA,Balasubramanian S,Witt RM,Nazemi KJ,Choi Y,Pazyra-Murphy MF,Walsh CO,Thompson M,Segal RA. Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses. Nat Neurosci 2009; 12:409-17. PubMed
  • Ha J,Lo KW,Myers KR,Carr TM,Humsi MK,Rasoul BA,Segal RA,Pfister KK. A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes. J Cell Biol 2008; 181:1027-39. PubMed
  • Pazyra-Murphy MF,Segal RA. Preparation and maintenance of dorsal root ganglia neurons in compartmented cultures. J Vis Exp 2008. PubMed
  • Zhou P, Porcionatto M, Pilapil M, Chen Y, Choi Y, Tolias KF, Bikoff JB, Hong EJ, Greenberg ME, Segal RA. Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors. Neuron 2007; 55:53-68. PubMed
  • Redjal N, Chan JA, Segal RA, Kung AL. CXCR4 inhibition synergizes with cytotoxic chemotherapy in gliomas. Clin Cancer Res 2006; 12:6765-71. PubMed
  • Redjal N, Chan JA, Segal RA, Kung A. CXCR4 inhibtion syniergizes with cytotoxic chemotherapy in gliomas. J Am Diet Assoc 2006; In Press:In Press.
  • Rubin JB, Kung AL, Klein RS, Chan JA, Sun Y, Schmidt K, Kieran MW, Luster AD, Segal RA. A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci U S A 2003; 100:13513-8. PubMed