Shanthini Sockanathan
725 N. Wolfe Street
PCTB 1004
Baltimore MD 21205
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 is 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.
We have for many years focused on understanding the mechanisms that underlie neuronal and glial differentiation during development. However, in the last few years, our interests have largely centered on understanding the physiological pathways that keep neurons alive. By doing so, we hope to gain insight into the molecular mechanisms that contribute to sporadic neurodegenerative diseases, which make up more than 90% of diseases such as Alzheimer’s Disease and Amyotrophic Lateral Sclerosis (ALS).
Our lab utilizes an integrated approach that includes in vivo and in vitro models, iPSC-derived neurons, imaging, cell biology, biochemistry, molecular biology, genetics, and behavior. Please click on the link for our Lab Website for more information.
Zhang N, Westerhaus A, Wilson M, Wang E, Goff L, Sockanathan S. Physiological regulation of neuronal Wnt activity is essential for TDP-43 localization and function. EMBO J. 2024. Epub 2024/06/26. doi: 10.1038/s44318-024-00156-8. (PMID: 38918634).
Levy-Myers R, Daudelin D, Na CH, and Sockanathan S. An independent regulator of global release pathways in astrocytes generates a subtype of extracellular vesicles required for postsynaptic function. Science Adv. 2023 Jun; 9(25): eadg2067. doi: 10.1126/sciadv.adg2067. PMCID: PMC10289663
Daudelin D, Westerhaus A, Zhang N, Leyder E, Savonenko A and Sockanathan S. Loss of GDE2 leads to complex behavioral changes including memory impairment. Behavioral and Brain Functions 2024 20:7. doi.org/10.1186/s12993-024-00234-1.
Westerhaus A, Joseph T, Meyers AJ, Jang Y, Na CH, Cave C, Sockanathan S. (2022) The distribution and function of GDE2, a regulator of spinal motor neuron survival, are disrupted in Amyotrophic Lateral Sclerosis. Acta Neuropathol Commun. May 12;10(1):73. (PMID: 35550203; PMCID: PMC9102353).
Nakamura M, Li Y, Choi BR, Matas-Rico E, Troncoso J, Takahashi C, Sockanathan S. GDE2-RECK controls ADAM10 α-secretase-mediated cleavage of amyloid precursor protein. Sci Transl Med. 2021 Mar 17;13(585):eabe6178. doi: 10.1126/scitranslmed.abe6178. PMID: 33731436.
Choi BR, Dobrowolski M, Sockanathan S. GDE2 expression in oligodendroglia regulates the pace of oligodendrocyte maturation. Dev Dyn. 2020 Oct 23. doi: 10.1002/dvdy.265. PMID: 33095500.
Choi BR, Cave C, Na CH, Sockanathan S. GDE2-Dependent Activation of Canonical Wnt Signaling in Neurons Regulates Oligodendrocyte Maturation. Cell reports. 2020 May 5;31(5):107540. PMID: 32375055 PMCID: PMC7254694 DOI: 10.1016/j.celrep.2020.107540
Dobrowolski M, Cave C, Levy-Myers R, Lee C, Park S, Choi BR, Xiao B, Yang W, Sockanathan S. (2020) GDE3 regulates oligodendrocyte precursor proliferation via release of soluble CNTFRα. Development. Jan 23;147(2). (PMCID: PMC6983723).
Choi BR, Cave C, Na CH, Sockanathan S. (2020) GDE2-dependent activation of canonical Wnt signaling in neurons regulates oligodendrocyte maturation. Cell Reports. May 5; 31 (5) 107540. (PMCID in progress).
Cave C, Park S, Rodriguez M, Nakamura M, Hoke A, Pletnikov M, Sockanathan S. GDE2 is essential for neuronal survival in the postnatal mammalian spinal cord. Mol Neurodegener. 2017 Jan 19;12(1):8. doi: 10.1186/s13024-017-0148-1
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
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.
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.
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.
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).
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)
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)
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)
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)
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.
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.
Rao, M. and Sockanathan, S. (2005) Transmembrane protein GDE2 induces motor neuron differentiation in vivo. Science 309, 2212-2215.
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
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.
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.
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.
Sockanathan S. and Jessell TM. (1998) Motor neuron-derived retinoid signaling specifies the subtype identity of spinal motor neurons.Cell 94, 503-14.