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Faculty Detail    
Name JOHN J SHACKA
  
Campus Address VH 257 Zip 0019
Phone  (205) 996-7252
E-mail  shacka@uab.edu
Other websites
     

Education
Undergraduate  Virginia Tech    1991  BS Biochemistry and BS Biology 
Graduate  VCU    1997  PhD Pharmacology and Toxicology 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pharmacology/Toxicology Chair's Office  Pharmacology/Toxicology Chair's Office Associate Professor
Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Assistant Professor
Center  Alzheimer's Disease Center  Alzheimer's Disease Center Associate Professor
Center  Center for AIDS Research  Center for AIDS Research Associate Professor
Center  Comprehensive Neuroscience Center  Comprehensive Neuroscience Center Associate Professor
Center  Ctr for Clinical & Translational Sci  Ctr for Clinical & Translational Sci Associate Professor
Center  Ctr Neurodegeneration & Exp Ther (CNET)  Ctr Neurodegeneration & Exp Ther (CNET) Associate Professor
Center  GL Ctr for Craniofacial, Oral, & Dental Disorders  GL Ctr for Craniofacial, Oral, & Dental Disorders Associate Professor
Center  Integrative Center for Aging Research  Integrative Center for Aging Research Associate Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Molecular and Cellular Pathology Program 
Neuroscience 
Pathobiology and Molecular Medicine 

Biographical Sketch 
John Shacka received B.S. degrees in Biochemistry and Biology from Virginia Tech in 1991 and in 1997 received his Ph.D. in Pharmacology and Toxicology from the Medical College of Virginia Campus of Virginia Commonwealth University. After postdoctoral fellowships at NCI/NIH and at UAB, he joined faculty in the Dept. Pathology in 2009. He is currently an Assistant Professor in the Molecular and Cellular Pathology Division. The Shacka Lab studies the therapeutic potential for molecular targets in the autophagy-lysosome pathway to promote the clearance of toxic proteins that accumulate in experimental models of Parkinson's disease.

Society Memberships
Organization Name Position Held Org Link
Alpha Chi Sigma Professional Chemistry Fraternity  Member  http://www.alphachisigma.org 
The Histochemical Society  Member  http://www.histochemicalsociety.org 
The Society for Neuroscience  Member  http://www.sfn.org 
 



Research/Clinical Interest
Title
Targeting the Autophagy-Lysosome Pathway for Therapeutic Benefit in Parkinson's Disease
Description
The autophagy lysosome pathway (ALP) shuttles long-lived and/or damaged proteins and organelles to lysosomes for enzymatic degradation and recycling. The ALP thus provides energy to the cell and maintains intracellular quality control. Although the ALP is ordinarily a cell survival pathway, its function decreases with normal brain aging and in neurodegenerative diseases. Our lab studies ALP dysfunction in Parkinson’s disease (PD) and how it may contribute to the pathological accumulation of alpha-synuclein, a protein that has also been proposed to regulate PD pathogenesis. The Shacka Lab uses a combined in vitro (cell culture, genetic and biochemical assays) and in vivo (experimental animal models) approach to identify and validate candidate molecular targets for their ability to enhance the clearance of proteins that contribute to PD pathogenesis. In addition, we have recently initiated studies with postmortem and premortem tissues from PD patients with the ultimate goal of validating ALP-associated molecules as biomarkers for PD. We hope that these pre-clinical and translational investigations focused on ALP-specific molecules will elucidate rational therapeutic strategies that will ultimately delay the onset and progression of PD and other age-related neurodegenerative diseases.

Selected Publications 
Publication PUBMEDID
El-Hage N, Rodriguez M, Dever SM, Masvekar RR, Gewirtz DA, Shacka JJ. HIV-1 and morphine regulation of autophagy in microglia: limited interactions in the context of HIV-1 infection and opioid abuse. Journal of Virology. 89(2): 1024-35, 2015.  25355898 
Mangieri LR*, Mader BJ*, Thomas CE, Taylor CA, Luker AM, Tse TE and 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  24695574 
Nelson, M.P., Tse, T.E., O’Quinn, D.B., Percival, S.M., Jaimes, E.A., Warnock, D.G. and Shacka, J.J. Autophagy-Lysosome Pathway-Associated Neuropathology and Axonal Degeneration in the Brains of Alpha-Galactosidase A-Deficient Mice. Acta Neuropathologica Communications, 2(1): 20, 2014  24529306 
Nelson, M.P. and Shacka, J.J. Autophagy Modulation in Disease Therapy: where do we stand? Curr. Pathobiol Rep., 1:239-245, 2013.  24470989 
Harms, A., Cao, S., Rowse, A., Thome, A., Li, X., Mangieri, L., Cron, R., Shacka, J., Raman, C. and Standaert, D. MHCII is required for Alpha-Synuclein Induced Activation of Microglia, CD4 T Cell Proliferation and Dopaminergic Neurodegeneration, J. Neurosci., 33:9592-9600, 2013  23739956 
Suswam, E, Shacka, JJ, Walker, K, Lu, L, Li, X, Si, Y, Zhang, X, Cao, H and King, PH. Mutant Tristetraprolin: a Potent Inhibitor of Malignant Glioma Cell growth. J. Neurooncol. 2013, 113:195-205, 2013.  23525947 
Yan J, Bansal A, Sabbaj S, Shacka JJ, Goepfert PA, and Heath SL. HIV specific CD8+ T cells from Elite Controllers are Primed for Survival. J Virol, 2013: 87 (9): 1-14.  23449791 
Gurpinar E, Grizzle WE, Shacka JJ, Mader BJ, Li N, Piazza NA, Russo S, Keeton AB, and Piazza GA. A novel sulindac derivative inhibits lung adenocarcinoma cell growth through suppression of Akt/mTOR signaling and induction of autophagy. Molecular Cancer Therapeutics, 2013 12:663-674, 2013.  23443799 
Mader, BJ, Pivtoraiko, VN, Flippo, HM, Klocke, BJ, Roth, KA, Mangieri, LR and Shacka, JJ. Rotenone Inhibits Autophagic Flux Prior to Inducing Cell Death. ACS Chemical Neuroscience, 3:1063-1072, 2012.  23259041 
Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K …Shacka, JJ, …Zuckerbraun B (approximately 1270 authors). Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy, 8:445-544, 2012.   22966490 
Shacka, JJ. Mouse Models of Neuronal Ceroid Lipofuscinoses: Useful Pre-Clinical Tools to Delineate Disease Pathophysiology and Validate Therapeutics. Brain Research Bulletin. 2012 88:43-57, 2012.  22502604 
Hoffman WH, Shacka JJ, and Andjelkovic, AV. Autophagy in the brains of young patients with poorly controlled T1DM and fatal diabetic ketoacidosis. Experimental and Molecular Pathology 93:273-280, 2011.  22079479 
Pivtoraiko, VN, Harrington, AJ, Luker, AM, Caldwell, GA, Caldwell, KA, Roth, KA, and Shacka, JJ. Low-dose Bafilomycin Attenuates Neuronal Cell Death Associated with Autophagy-Lysosome Pathway Dysfunction. Journal of Neurochemistry 114:1193-204, 2010.  20534000 
Walls, KC, Ghosh, AP, Franklin, AL, Klocke, BJ, Ballestas, M, Shacka, JJ, Zhang, J, and Roth, KA. Lysosome dysfunction triggers Atg7-dependent neural apoptosis. Journal of Biological Chemistry 285:10497-507, 2010.  20123985 
Yang Q, She H, Gearing M, Colla E, Lee M, Shacka JJ, Mao Z. Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy. Science 323:124-7, 2009.  19119233 
Qiao L, Hamamichi S, Caldwell KA, Caldwell GA, Yacoubian TA, Wilson S, Xie ZL, Speake LD, Parks R, Crabtree D, Liang Q, Crimmins S, Schneider L, Uchiyama Y, Iwatsubo T, Zhou Y, Peng L, Lu Y, Standaert DG, Walls KC, Shacka JJ, Roth KA, Zhang J. Lysosomal enzyme chathepsin D protects against alpha-synuclein aggregation and toxicity. Mol Brain 1:1-17, 2008.
PMCID: PMC2600785 		 19021916 
Pivtoraiko VN, Stone SL, Roth KA, Shacka JJ. Oxidative Stress and Autophagy in the Regulation of Lysosome-Dependent Neuron Death. Antioxid Redox Signal 11:481-96, 2009.  18764739 
Majumdar D, Maunsbach AB, Shacka JJ, Williams JB, Berger UV, Schultz KP, Harkins LE, Boron WF, Roth KA, Bevensee MO. Neuroscience 155:818-32, 2008.  18582537 
Slemmer JE, Shacka JJ, Sweeney MI, Weber JT. Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr Med Chem 15:404-14, 2008.  18288995 
Suswam E, Li Y, Zhang X, Gillespie GY, Li X, Shacka JJ, Zheng L, King PH. Tristetraprolin down-regulates interleukin-8 and vascular endothelial growth factor in malignant glioma cells. Cancer Res 68:674-82, 2008.  18245466 
Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G...Shacka JJ,...Deter RL (over 200 authors). Guidelines forthe use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4:151-75, 2008.
PMCID: PMC2654259 		 18188003 
Shacka JJ, Roth KA, Zhang J. The autophagy-Lysosomal degradation pathway: role in neurodegenerative disease and therapy. Front Biosci 13:718-36, 2008.  17981582 
Shacka JJ, Roth KA. Cathepsin D deficiency and NCL/Batten disease: there's more to death than apoptosis. Autophagy 3:474-6, 2007.  17495518 
Shacka, JJ, Klocke, BJ, Young, C, Shibata, M, Olney, JW, Uchiyama, Y, Saftig, P and Roth, KA Cathepsin D Deficiency Induces Persistent Neurodegeneration in the Absence of Bax-Dependent Apoptosis. The Journal of Neuroscience 27:2081-90, 2007.  17314303 
Walls, KC, Klocke, BJ, Saftig, P, Shibata, M, Uchiyama, Y, Roth, KA and Shacka, JJ. Altered Regulation of Phosphatidylinositol 3-Kinase Signaling in Cathepsin D-Deficient Brain. Autophagy 3:222-29, 2007.  17297299 
Shacka, JJ, Lu, J, Xie, X-L, Uchiyama, Y, Roth, KA and Zhang, J. Kainic Acid Induces Early and Transient Autophagic Stress in Mouse Hippocampus. Neuroscience Letters 414:57-60, 2007. PMCID: PMC1839881  17223264 
Geng, Y, Akhtar, RS, Shacka, JJ, Klocke, BJ, Zhang, J, Chen, X and Roth, KA. P53 transcription-dependent and –independent regulation of cerebellar neural precursor cell apoptosis. Journal of Neuropathology and Experimental Neurology 66:66-74, 2007.  17204938 
Ye, YZ, Quijano, C, Robinson, KM, Ricart, KC, Strayer, AL, Sahawneh, MA, Shacka, JJ, Kirk, M, Barnes, S, Accavitti-Loper, MA, Radi, R, Beckman, JS and Estévez, AG. Prevention of peroxynitrite-induced apoptosis of motor neurons and PC12 cells by tyrosine-containing peptides. Journal of Biological Chemistry 282:6324-37, 2007.   17200124  
Shacka, JJ, Klocke, BJ and Roth, KA. Autophagy, Bafilomycin and Cell Death: The “A-B-Cs” of Plecomacrolide-Induced Neurodegeneration. Autophagy 2:228-230, 2006.  16874105 
Shacka, JJ and Roth, KA Bcl-2 Family and the Central Nervous System: From Rheostat to Real Complex. Cell Death and Differentiation 13:1299-1304, 2006.
 		 16729026 
Shacka, JJ, Sahawneh, MA, Gonzalez, JD, Ye, YZ, D’Allesandro, TL and Estévez, AG. Two distinct signaling pathways regulate peroxynitrite-induced apoptosis in PC12 cells. Cell Death and Differentiation 13:1506-1514, 2006.  16410804 
Shacka, JJ, Klocke, BJ, Shibata, M, Uchiyama, Y, Datta, G, Schmidt, RE and Roth, KA. Bafilomycin A1 inhibits chloroquine-induced neuronal cell death. Molecular Pharmacology 69:1125-1136, 2006.  16391239 
Shacka , JJ and Roth, KA. Cathepsin deficiency as a model for neuronal ceroid lipofuscinosces. American Journal of Pathology. 167:1473-1476, 2005.  16314462 
Shacka, JJ and Roth, KA. Regulation of neuronal cell death and neurodegeneration by members of the Bcl-2 family: therapeutic implications. Current Drug Targets-CNS & Neurological Disorders. 4:25-39, 2005.  15723611 
Peluffo, H, Shacka, JJ, Ricart, K, Bisig, CG, Martinez-Palma, L, Pritsch, O, Kamaid, A, Eiserich, JP, Crow, JP, Barbeito, L and Estévez, AG. Induction of motor neuron apoptosis by free 3-nitro-L-tyrosine. Journal of Neurochemistry. 89:602-612, 2004.  15086517 
Yu, X, Shacka, JJ, Eells, JB, Suarez-Quian, C, Przygodzki, RM, Beleslin-Cokic, B, Lin, C-S, Nikodem, VM, Hempstead, B, Flanders, KC, Constantini, F and Noguchi, CT. Erythropoietin receptor signaling is required for normal brain development. Development 129:505-16, 2002.  11807041 
 

Keywords
Autophagy; Lysosome; Parkinson's; Synuclein; Alpha-Galactosidase