Rosalind Segal
Rosalind Segal, M.D., Ph.D.
Professor of Neurobiology

Sensory Neurons

The nervous system inputs sensory information, processes that information, and executes actions, so we can interact with the world around us. Several specialized attributes of sensory neurons enable input of information about our surroundings: these neurons have distinctive nerve endings that are in close contact with the external environment, their axons traverse great distances and they are able to transmit information rapidly and unidirectionally. Much of our research focuses on the largest set of primary sensory neurons, the dorsal root ganglia (DRG) neurons that innervate the skin and transmit sensations of touch, pain, temperature and motion.

• How is gene expression regulated in distinct intracellular sites within large sensory neurons?

Sensory neurons traverse long distances. However it is not known how proteins are differentially localized within distinct intracellular domains of sensory neurons, so that peripheral axons can initiate tactile sensation and central axons can form synapses in the spinal cord. Recent studies have highlighted the importance of mRNA transport and localized protein synthesis in spatial regulation of gene expression. We have identified mRNAs that are localized and translated in the peripheral axons of sensory neurons. We are addressing how RNA binding proteins orchestrate mRNA trafficking and protein expression within peripheral terminals and so enable tactile sensation.

• How do long peripheral axons withstand damage so they are maintained throughout life?

We identified the bcl2 family member bclw as an anti-apoptotic component highly expressed in axons of sensory neurons, and we demonstrated that loss of bclw results in progressive, sensory neuropathy due to axonal degeneration.  Current studies to define mechanisms that regulate bclw expression, and to determine how bclw exerts its distinctive ability to promote axon viability and prevent axon degeneration may lead to new therapeutic approaches for degenerative disorders that impact sensory neurons.

Brain Tumor Biology

A major project in the laboratory focuses on brain tumor biology.  Brain tumors now represent the most common cause of cancer-related death in children.  New genomic insights identify several key pathways that promote regulated growth during development, and also contribute to deregulated growth of pediatric brain tumors, including the Sonic Hedgehog (Shh) pathway. Our studies focus on the biology of the Shh signaling pathway in development and disease. Current studies are aimed at developing therapeutic approaches to pediatric brain tumors by targeting novel components in the Shh signaling cascade or by targeting synergistic signaling pathways.

 

"Several specialized attributes of sensory neurons enable input of information about our surroundings."

Publications View
Pathogenesis of paclitaxel-induced peripheral neuropathy: A current review of in vitro and in vivo findings using rodent and human model systems.
Authors: Authors: Staff NP, Fehrenbacher JC, Caillaud M, Damaj MI, Segal RA, Rieger S.
Exp Neurol
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Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.
Authors: Authors: Reitman ZJ, Paolella BR, Bergthold G, Pelton K, Becker S, Jones R, Sinai CE, Malkin H, Huang Y, Grimmet L, Herbert ZT, Sun Y, Weatherbee JL, Alberta JA, Daley JF, Rozenblatt-Rosen O, Condurat AL, Qian K, Khadka P, Segal RA, Haas-Kogan D, Filbin MG, Suva ML, Regev A, Stiles CD, Kieran MW, Goumnerova L, Ligon KL, Shalek AK, Bandopadhayay P, Beroukhim R.
Nat Commun
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A large-scale drug screen identifies selective inhibitors of class I HDACs as a potential therapeutic option for SHH medulloblastoma.
Authors: Authors: 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.
Neuro Oncol
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NCI Clinical Trials Planning Meeting for prevention and treatment of chemotherapy-induced peripheral neuropathy.
Authors: Authors: 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.
J Natl Cancer Inst
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Sonic Hedgehog Signaling is Blue: Insights from the Patched Mutant Mice.
Authors: Authors: Merk DJ, Segal RA.
Trends Neurosci
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A transatlantic cooperation for enriched neuroscience training.
Authors: Authors: Witter MP, Karagogeos D, Van Bockstaele EJ, Segal RA.
Eur J Neurosci
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A Transposon Screen Identifies Loss of Primary Cilia as a Mechanism of Resistance to SMO Inhibitors.
Authors: Authors: Zhao X, Pak E, Ornell KJ, Pazyra-Murphy MF, MacKenzie EL, Chadwick EJ, Ponomaryov T, Kelleher JF, Segal RA.
Cancer Discov
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Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration.
Authors: Authors: Pease-Raissi SE, Pazyra-Murphy MF, Li Y, Wachter F, Fukuda Y, Fenstermacher SJ, Barclay LA, Bird GH, Walensky LD, Segal RA.
Neuron
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A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas.
Authors: Authors: 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.
Neuro Oncol
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A Mechanistic Understanding of Axon Degeneration in Chemotherapy-Induced Peripheral Neuropathy.
Authors: Authors: Fukuda Y, Li Y, Segal RA.
Front Neurosci
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