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BCMBJHU SOM

Faculty & Research

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Shanthini Sockanathan

Department Affiliation Primary: Neuroscience
RankProfessor
Phone Numbers410-502-3084
Lab: 410-502-3085
Emailssockan1@jhmi.edu
School of Medicine Address725 N. Wolfe Street
PCTB 1004
Baltimore MD 21205
Link to Lab Homepage
Shanthini Sockanathan

Research Topic: Cell fate specification in the central nervous system

​The nervous system consists of a great variety of neurons and glia that together form the components and circuits necessary for nervous system function. Neuronal and glial diversity are generated through a series of highly orchestrated events that control cell numbers, subtype identity, cell morphology and axonal projection patterns.  Although glial cells remain proliferative throughout life, the number of neurons remains largely finite, with the exception of small pockets of adult neurogenesis in the brain. Loss of neurons through injury or disease consequently leads to abnormal circuit function, and depending upon the site of loss, corresponding deficits in cognition, motor function and sensory processing.


Questions we are interested in answering encompass both development and disease. Specific questions include:

  • What are the molecular mechanisms that regulate neuronal and glial differentiation during development?
  • What are the pathways that keep neurons alive and how might they be impacted in neurodegenerative diseases?
  • Are the same or different pathways altered in distinct neurodegenerative diseases such as ALS (Lou Gehrig’s disease) or Alzheimer’s disease (AD)?

To solve these questions, we utilize an integrated approach that includes in vivo models, imaging, molecular biology, cell biology, biochemistry, developmental biology, genetics and behavior. The major focus of the lab is the study of a new family of six-transmembrane proteins (6-TM GDEs) that play key roles in regulating cellular differentiation and survival in the spinal cord. We recently discovered that the 6-TM GDEs release GPI-anchored proteins from the cell surface through cleavage of the GPI-anchor. This discovery identifies 6-TM GDEs as the first membrane bound GPI-anchor cleaving enzymes in vertebrates that work at the cell surface to regulate GPI-anchored protein function. Current work in the lab studies how the 6-TM GDEs regulate signaling events that control neuronal and glial differentiation during development, together with a new major focus on how GDE dysfunction relates to the onset and progression of neurodegeneration with relevance to ALS and AD.

Publications:

Yan, Y, Wldayka, C., Fujii, J., and Sockanathan, S. (2015) Prdx4 is a compartment-specific H2O2 sensor that regulates neurogenesis by controlling surface expression of GDE2. Nature Comm. 6; 6:7006
PubMed Reference

Choi, J.H., Park, S.J. and Sockanathan, S. (2014) Activated retinoid receptors are required for the migration and fate maintenance of subsets of cortical neurons. Development 141, 1151-1160.
PubMed Reference

Park, S., Lee, C., Sabharwal, P., Zhang, M., Freel Meyers, C., and Sockanathan S. (2013) GDE2 promotes neurogenesis by glycosylphosphatidylinositol-anchor cleavage of RECK. Science 339, 324-328.
PubMed Reference

Rodriguez, M., Choi, J., Park, S., and Sockanathan, S. (2012). GDE2 regulates cortical neuronal identity by controlling the timing of cortical progenitor differentiation. Development 139, 3870-3879.
PubMed Reference

Sabharwal, P., Lee, C., Park, S., Rao, M., and Sockanathan, S.  (2011) GDE2 Regulates Subtype-Specific Motor Neuron Generation through Inhibition of Notch Signaling. Neuron 71, 1058-1070. (PMCID: PMC3183458).
PubMed Reference

Periz, G, Yan, Y., Bitzer, Z.T. and Sockanathan, S. (2010) GDP-bound Gi2 regulates spinal motor neuron differentiation through interaction with GDE2. Dev. Bio. 341, 213-221 (NIHMS:185579)
PubMed Reference

Yan, Y., Sabharwal, P., Rao, M., and Sockanathan, S. (2009) The antioxidant Prdx1 controls motor neuron differentiation by thiol-redox dependent activation of GDE2. Cell 138, 1209-1221. (NIHMS:131140)
PubMed Reference

Zhuang, B.Q., Su, Y.S., and Sockanathan, S. (2009) FARP1 promotes the dendritic growth of spinal motor neuron subtypes through ttransmembrane Semaphorin6A and PlexinA4 signaling. Neuron 61, 359-372. (NIHMS: 96378)
PubMed Reference

Ji, S.J., Periz, G., and Sockanathan, S. (2009) Nolz1 is induced by retinoid signals and controls motor neuron subtype identity through distinct repressor activities. Development 136, 231-240. (NIHMS:161591)
PubMed Reference

Rajaii, F., Bitzer, Z.T., Qing, X. and Sockanathan, S. (2008) Expression of the dominant negative retinoid receptor, RAR403, alters telencephalic progenitor proliferation, survival and fate specification. Dev.Bio. 316, 371-382.
PubMed Reference

Ji SJ, Zhuang B, Falco C, Schneider A, Schuster-Gossler K, Gossler A and Sockanathan S. (2006) Mesodermal and neuronal retinoids regulate the induction and maintenance of limb innervating spinal motor neurons. Dev Biol. 297, 249-61.
PubMed Reference

Rao, M. and Sockanathan, S. (2005) Transmembrane protein GDE2 induces motor neuron differentiation in vivo. Science 309, 2212-2215.
PubMed Reference

Rao M, Baraban J, Rajaii F and Sockanathan S. (2004) In vivo comparative study of RNAi methodologies by in ovo electroporation in the chick embryo. Dev. Dynamics 231, 592-600.
PubMed Reference


Sockanathan S., Perlmann T and Jessell TM. (2003) Retinoid receptor signaling in postmitotic motor neurons regulates rostrocaudal positional identity and axonal projection pattern. Neuron 40, 97-111.
PubMed Reference

Novitch B,  Wichterle H, Jessell TM and Sockanathan S. (2003) A requirement for retinoic acid mediated transcriptional activation in ventral neural tube patterning and motor neuron specification. Neuron 40, 81-95.
PubMed Reference

Arber S, Han B, Smith M, Mendelsohn M, Jessell TM and Sockanathan S. (1999). Requirement for the Homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron 23, 659-674.
PubMed Reference

Sockanathan S. and Jessell TM. (1998) Motor neuron-derived retinoid signaling specifies the subtype identity of spinal motor neurons.Cell 94, 503-14.
PubMed Reference​

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