The Palladino lab uses Drosophila and human cell lines as model systems to elucidate the cellular and molecular mechanisms of neurodegenerative diseases. Our lab has identified numerous novel neurodegenerative mutants using forward genetics and developed these as unique disease models. Our research program forces on metabolic disease and the neuromuscular dysfunction they produce with three main goals: 1) discovering and characterizing novel pathways that cause disease, 2) understanding the physiological, cellular, and molecular dysfunction that causes disease in vivo, and 3) using our animal system in pharmacological screens to identify neuroprotective compounds for the treatment of human diseases. We are currently focusing on elucidating the mechanism by which mutations affecting triose phosphate isomerase (TPI) and mtATP6 function result in glycolytic enzymopthy and mitochondrial encephalaomyopathy, respectively. We are also funded to develop the methodology to use our neurodegenerative mutants in pharmacological screens to identify novel neuroprotectant compounds. To this end we’ve developed a high throughput drug screening platform using a semi-automated optical screening method to identify novel treatments for TPI Deficiency. We also have the only patient cells including iPS cells of this rare childhood degenerative disease.
Liu, Z., Celotto, A,M., Romero, G., Wipf, P. and Palladino, M.J. Genetically encoded redox sensor identifies the role of ROS in degenerative and mitochondrial disease pathogenesis. Neurobiology of Disease, 45(1): 362-8, 2012.
Celotto, A,M., Liu, Z., VanDemark, A. P. and Palladino, M.J. A novel Drosophila SOD2 mutant demonstrates a role for mitochondrial ROS in neurodevelopment and disease. Brain and Behavior, 2(4): 423-34, 2012.
Celotto, A,M., Chiu, W.K., Van Voorhies, W. and Palladino, M.J. Modes of Metabolic Compensation during Mitochondrial Disease Using the Drosophila Model of ATP6 Dysfunction. PLoS ONE 6(10): e25823, 2011.
Hrizo, S.L. and Palladino, M.J. Hsp70 and Hsp90 mediate proteasomal degradation of TPIsugarkill that underlies pathogenesis. Neurobiology of Disease 40:676-683, 2010.
Ashmore LJ, SL Hrizo, SM Paul, W Van Voorhies, GJ Beitel and MJ Palladino. Novel mutations affecting the NA,K ATPase alpha model complex neurological diseases and implicate the sodium pump in increased longevity. Human Genetics 126: 431-447, 2009.
Celotto, A,M., Frank, A,C., McGrath, S.W., Fergestad, T.J., Van Voorhies, W.A., Buttle, K., Mannella, C.A., and Palladino, M.J. Mitochondrial encephalomyopathies in drosophila. Journal of Neuroscience 26(3): 810-820, 2006.
Palladino, M.J., JE Bower, R Kreber and Barry Ganetzky. Neural dysfunction and neurodegeneration in Drosophila Na+/K+ ATPase alpha subunit mutants. Journal of Neuroscience 23(4): 1276-1286, 2003.
Palladino, M.J., Keegan, L.P., O'Connell, M.A. and Reenan, R.A. A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity. Cell 102(4): 437-449, 2000.