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My laboratory is interested in determining mechanisms that control organelle organization and trafficking in neurons and cause(s) of neurological disorders. For example, mitochondria integrate their apparently dissimilar functions (energy metabolism, motility and programmed cell death), and synergistically respond to exogenous perturbations. This mitochondrial synergy with their functions is vital along the long neuronal processes, where mitochondria are critically positioned. By using cellular, biochemical, molecular biology techniques and state-of-the art microscopy, we are studying how alcohol-induced oxidative stress alters mitochondrial dynamics. Alcohol is simply used as a model system, given the clear link between alcohol and oxidative stress. The temporal movement and spatial distribution of mitochondria in cells has the potential to develop into a tool to differentiate between healthy and diseased cells.
Related projects in the laboratory are focused on elucidating the role of mitochondrial fusion, fission and biogenesis and antioxidant status in neuro-degeneration. Mitochondrial biogenesis is under the direct control of a transcription factor, PGC1-α. We are studying the regulation of PGC1-α under conditions of oxidative stress and if these mechanism(s) are reversible.
- Zhang Y, Chang FM, Huang J, Junco JJ, Maffi SK, Pridgen HI, Dang H, Trempus CS, Kim DJ, Slaga TJ and Wei SJ. DSS1, DSS1, a Novel Modifier Tagging Proteins for Their Degradation in Cells under Oxidative Stress. Protein Cell, 2014: In press Published online in Feb
- Contreras-Shannon V, Heart DL, Navaira E, Catano G, Maffi SK and Walss-Bass C. Clozapine-induced mitochondria alterations and inflammation in brain and insulin-responsive cells. PLoSOne. 8(3): e59012, 2013. PMCID: PMC3604003
- Cheng B, Martinez AA, Morado J, Roberts JL and Maffi SK. Retinoic Acid reverses proteasome inhibition-induced cytotoxicity in SH-SY5Y Cells via the AKT pathway. Neurochem Int. Jan;62(1):31-42, 2013.
- Chang FM, Reyna SM, Granados JC, Wei S-J, Innis-Whitehouse W, Rodriguez E, Maffi SK, Slaga TJ and Short JD. Inhibition of neddylation represses LPS-induced proinflammatory cytokine production in macrophage cells. J Biol Chem. 287(42):35756-67. 2012. PMCID: PMC3471689