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 projections. Dr. Sockanathan works to define how these events unfold and integrate at the molecular level to provide insight into the basic mechanisms involved in establishing and maintaining the mature nervous system, and importantly provide an understanding of the links between development, disease and therapeutic strategies.
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 neuronal survival. Dr Sockanathan's lab discovered that the 6-TM GDEs release GPI-anchored proteins from the cell surface through cleavage of the GPI-anchor. This discovery identified the 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.
Lab Website: Sockanathan Lab
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
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.
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.
Nakamura M, Li YH, Choi B-R, Matas-Rico E, Troncoso J, Takahashi J, Sockanathan S. GDE2-RECK controls ADAM10 α secretase-mediated cleavage of amyloid precursor protein. Science Translational Medicine. 2021 mar17;13 (585)doi: 10.1126/scitranslmed.abe6178
Choi B-R, Cave C, Na CH, Sockanathan S. GDE2-Dependent Activation of Canonical Wnt Signaling in Neurons Regulates Oligodendrocyte Maturation. Cell Rep. 2020 May 5; 31(5): 107540. doi: 10.1016/j.celrep.2020.107540