Rosalind Segal
Rosalind Segal, MD, PhD
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
TMEM161B regulates cerebral cortical gyration, Sonic Hedgehog signaling, and ciliary structure in the developing central nervous system.
Authors: Authors: Akula SK, Marciano JH, Lim Y, Exposito-Alonso D, Hylton NK, Hwang GH, Neil JE, Dominado N, Bunton-Stasyshyn RK, Song JHT, Talukdar M, Schmid A, Teboul L, Mo A, Shin T, Finander B, Beck SG, Yeh RC, Otani A, Qian X, DeGennaro EM, Alkuraya FS, Maddirevula S, Cascino GD, Giannini C, Burrage LC, Rosenfield JA, Ketkar S, Clark GD, Bacino C, Lewis RA, Segal RA, Bazan JF, Smith KA, Golden JA, Cho G, Walsh CA.
Proc Natl Acad Sci U S A
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Sarm1 activation produces cADPR to increase intra-axonal Ca++ and promote axon degeneration in PIPN.
Authors: Authors: Li Y, Pazyra-Murphy MF, Avizonis D, de Sá Tavares Russo M, Tang S, Chen CY, Hsueh YP, Bergholz JS, Jiang T, Zhao JJ, Zhu J, Ko KW, Milbrandt J, DiAntonio A, Segal RA.
J Cell Biol
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Diversity of developing peripheral glia revealed by single-cell RNA sequencing.
Authors: Authors: Tasdemir-Yilmaz OE, Druckenbrod NR, Olukoya OO, Dong W, Yung AR, Bastille I, Pazyra-Murphy MF, Sitko AA, Hale EB, Vigneau S, Gimelbrant AA, Kharchenko PV, Goodrich LV, Segal RA.
Dev Cell
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Uncomfortably numb: how Nav1.7 mediates paclitaxel-induced peripheral neuropathy.
Authors: Authors: Silagi ES, Segal RA.
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The Eya1 Phosphatase Mediates Shh-Driven Symmetric Cell Division of Cerebellar Granule Cell Precursors.
Authors: Authors: 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.
Dev Neurosci
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Binding and transport of SFPQ-RNA granules by KIF5A/KLC1 motors promotes axon survival.
Authors: Authors: Fukuda Y, Pazyra-Murphy MF, Silagi ES, Tasdemir-Yilmaz OE, Li Y, Rose L, Yeoh ZC, Vangos NE, Geffken EA, Seo HS, Adelmant G, Bird GH, Walensky LD, Marto JA, Dhe-Paganon S, Segal RA.
J Cell Biol
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Understanding The Epigenetic Landscape and Cellular Architecture of Childhood Brain Tumors.
Authors: Authors: Veiga Cruzeiro GA, Rota C, Hack OA, Segal R, Filbin MG.
Neurochem Int
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Recognizing Team Science Contributions in Academic Hiring, Promotion, and Tenure.
Authors: Authors: Cline H, Coolen L, de Vries S, Hyman S, Segal R, Steward O.
J Neurosci
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An Architect of the Hindbrain: DDX3X Regulates Normal and Malignant Development.
Authors: Authors: Hwang GH, Segal RA.
Dev Cell
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Roadmap for the Emerging Field of Cancer Neuroscience.
Authors: Authors: 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.
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