Receptor seminar: Mechanisms and Interventions for Defective Intermediate Filament Proteostasis
Assistant prof. Natasha Snider, University of North Caroline, Chapel Hill, NC, USA
Host: Diana Toivola (dtoivola@abo.fi)
Dr. Snider’s reserach is focused on the molecular basis of liver diseases and disorders linked to intermediate filament gene mutations. Her team uses biochemical, cell-based and in vivo approaches to identify potential disease targets and to understand their function and regulation.
Their major goals are to promote the discovery of pharmacological agents that can slow or halt the progression of these diseases. The liver-related studies has linked liver injury susceptibility to the function of energy metabolism regulators, including the glycolytic enzyme GAPDH and the purine metabolizing enzymes nucleoside diphosphate kinase (NDPK) and ecto-5′-nucleotidase CD73. Their aims are to understand the regulation and cell-specific functions of CD73 in various stages of liver disease, including fibrosis, cirrhosis and hepatocellular carcinoma.
Another research interest is in the area of intermediate filaments and related diseases. Intermediate filament gene mutations are linked to a vast number of human pathologies, including skin fragility disorders, neuropathies, myopathies, liver diseases, metabolic dysfunctions, and premature aging syndromes. Effective treatments for diseases caused by intermediate filament gene mutations are lacking. The long-term goals are to define the proteostasis network of intermediate filament proteins and to identify key features compromised by disease-causing or disease-promoting mutations. A central research focus is on various post-translational modifications and their cross-talk mechanisms.
Selected publications
Trogden KP, Battaglia RA, Kabiraj P, Madden VJ, Herrmann H, Snider NT (2018). An image-based small molecule screen identifies vimentin as a pharmacologically relevant target of simvastatin in cancer cells. FASEB J. 32(5):2841-2854.
Battaglia RA, Kabiraj P, Willcockson HH, Lian M, Snider NT. (2017) Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications. J Vis Exp. (123). doi: 10.3791/55655.
Snider NT, Altshuler PA, Omary MB. (2015). Modulation of cytoskeletal dynamics by mammalian nucleoside diphosphate kinase (NDPK) proteins. Naunyn Schmiedebergs Arch Pharmacol. 388(2):189-197.
Snider NT and Omary MB (2016). Assays for post-translational modifications of intermediate filament proteins. Methods in Enzymology: Intermediate Filaments. 568:113-138.
Snider NT and Omary MB (2014). Post-translational modifications of intermediate filament proteins: function and regulation. Nat Rev Mol Cell Biol. 15:163-177.