The nervous system consists of a 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. Dr. Sockanathan works to define how these events unfold and integrate at the molecular level to provide significant insight into the basic mechanisms involved in establishing the mature nervous system, and importantly provide an understanding of the links between development, disease and therapeutic strategies.
Dr. Sockanathan’s laboratory uses the developing spinal cord as our major paradigm to define the mechanisms that maintain an undifferentiated progenitor state and the molecular pathways that trigger their differentiation into neurons and glia. 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 neuronal and glial differentiation in the spinal cord. They 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 vertebrate membrane bound GPI-cleaving enzymes that work at the cell surface to regulate GPI-anchored protein function. Current work in the lab involves defining how the 6-TM GDEs regulate cellular signaling events that control neuronal and glial differentiation and function, with a major focus on how GDE dysfunction relates to the onset and progression of disease. To solve these questions, they utilize an integrated approach that includes in vivo models, imaging, molecular biology, biochemistry, developmental biology, genetics and behavior.
Park S, Lee C, Sabharwal P, Zhang M, Meyers C, Sockanathan S. “GDE2 Promotes Neurogenesis by Glycosylphosphatidylinositol-Anchor Cleavage of Reck”. Science 339:324-339. 2013
Rodriguez M, Choi J, Park S, Sockanathan S. “Gde2 regulates cortical neuronal identity by controlling the timing of cortical progenitor differentiation”. Development 2012 Oct; 139(20):3870-9. Epub 2012 Sep 5
Sabharwal P, Lee C, Park S, Rao M, Sockanathan S. “GDE2 regulates subtype-specific motor neuron generation through inhibition of Notch signaling”. Neuron. 2011 Sep 22; 71(6):1058-70. Epub 2011 Sep 21.
Periz G, Yan Y, Bitzer ZT, Sockanthan S. “GDP-bound Galphai2 regulates spinal motor neuron differentiation through interaction with GDE2”. Dev Biol. 2010 May 1; 341(1):213-21. Epub 2010 Mar 1.
Ye Y, Sabharwal P, Rao M, and Sockanathan S. “The Antioxidant Enzyme Prdx1 Controls Neuronal Differentiation by Thiol-Redox-Dependent Activation of GDE2”. Cell 138:1209-1221.