My laboratory investigates the autophagy-lysosome pathway (ALP) in neurodegenerative diseases including Parkinson’s disease and HIV-associated neurocognitive disorder (HAND), and in the lysosomal storage disorder Fabry disease. Not only are we interested in delineating how ALP dysfunction may contribute to the pathogenesis of these diseases, but also how the ALP may be targeted as a source for disease-specific biomarkers and therapeutics development. Our research program includes preclinical (cell culture, mouse) studies in addition to translational studies with human specimens.

One of our recent accomplishments was a series of findings indicating an emerging relationship between deficiency of the lysosomal enzyme alpha-Galactosidase A (α-Gal A) and the pathologic accumulation of alpha-synuclein (α-syn), both in mice deficient in α-Gal A (A) and in postmortem Parkinson's disease brain (B, C). These findings have led to ongoing funded investigations to determine if α-Gal A regulates α-syn mediated neurotoxicity in preclinical models of Parkinson's disease.

I also maintain a strong teaching and service mission here at UAB. I teach several lectures/year to GBS students and currently serve on the UAB Investigational Biosafety Committee, the UAB Faculty Sustainability Committee. I also currently serve on the Research Safety Subcommittee at the Birmingham VA Medical Center.

Shacka JJ, Klocke BJ, Shibata M, Uchiyama Y, Datta G, Schmidt RE, Roth KA. Bafilomycin A1 prevents chloroquine-induced neuronal cell death. Molecular Pharmacology. 69: 1125-1136, 2006.

Walls KC, Klocke BA, Shibata M, Uchiyama Y, Saftig P, Roth KA, Shacka JJ. Altered regulation of phosphatidylinositol-3-kinase in cathepsin d-deficient brain. Autophagy. 3: 222-29, 2007.

Shacka JJ, Klocke BJ, Young C, Shibata M, Olney JW, Uchiyama Y, Saftig P, Roth KA. Persistent cathepsin d-deficiency-induced neurodegeneration in the absence of bax-dependent apoptosis. The Journal of Neuroscience. 27: 2081-90, 2007.

Pivtoraiko VN, Harrington AM, Mader BJ, Caldwell GA, Caldwell KA, Roth KA, Shacka JJ. Low-dose Bafilomycin Attenuates Neuronal Cell Death Associated with Autophagy-Lysosome Pathway Dysfunction. Journal of Neurochemistry. 114(4): 1193-204; 2010.

Mader BJ, Pivtoraiko VN, Flippo HM, Klocke BJ, Roth KA, Mangieri LR, Shacka JJ. Rotenone Inhibits Autophagic Flux Prior to Inducing Cell Death. ACS Chemical Neuroscience. 3: 1063-1072, 2012.

Harms A, Cao S, Rowse A, Thome A, Li X, Mangieri L, Cron R, Shacka J, Raman C, Standaert, D. MHCII is required for Alpha-Synuclein Induced Activation of Microglia, CD4 T Cell Proliferation and Dopaminergic Neurodegeneration. Journal of Neuroscience. 33 (23): 9592-9600, 2013.

Nelson MP, Tse TE, O’Quinn DB, Percival SM, Jaimes EA, Warnock DG, Shacka JJ. Autophagy-Lysosome Pathway-Associated Neuropathology and Axonal Degeneration in the Brains of Alpha-Galactosidase A-Deficient Mice. Acta Neuropathologica Communications. 2(1): 20, 2014.

Mangieri LR*, Mader BJ*, Thomas CE, Taylor CA, Luker AM, Tse TE, Shacka JJ. ATP6V0C Knockdown in Neuroblastoma Cells Alters Autophagy-Lysosome Pathway Function and Metabolism of Proteins that Accumulate in Neurodegenerative Disease (*co-first authors). PLOS One. 9(4): e93257, 2014

Boutin M, Sun Y, Shacka JJ, Auray-Blais C. Tandem Mass Spectrometry Multiplex Analysis of Glucosylceramide and Galactosylceramide Isoforms in Brain Tissues at Different Stages of Parkinson Disease. Anal. Chem. 88(3): 1856-63, 2016.

Vance D, Fazeli P, Shacka J, Nicholson W, McKie P, Raper J, Azuero A, Wadley V, Ball K. Testing a Computerized Cognitive Training Protocol in Adults Aging with HIV-Associated Neurocognitive Disorder: Randomized Controlled Trial Rationale and Protocol. Journal of Medical Internet Research: Research Protocols. 6:e68, 1-16, 2017.