ChadDickey

Chad Dickey, Ph.D.

Assoc Professor, College Of Medicine Molecular Medicine

College Of Medicine Molecular Medicine

Assistant Professor, Department of Molecular Medicine-University of South Florida, College of Medicine, Johnnie B. Byrd Sr. Alzheimer's Center and Research Institute

Contact Info 4001 E. Fletcher Ave. Rm# 338
USF Health Byrd Alzheimer's Insititute
Tampa, FL 33613

Academic Email: cdickey@health.usf.edu

Academic Phone: (813) 396-0639

Education

  • PHD, Pharmacology/Neuroscience, University Of South Florida, 2004
  • B.S., Microbiology, University of South Florida, 1998

Interdisciplinary and Emerging Signature Programs

  • Neuroscience

Research Interests

  • My research interests lie with the molecular mechanisms involved in protein turnover and degradation, particularly in the brain. My recent focus has been on the role of molecular chaperones in a group of diseases termed tauopathies, the most common of which is Alzheimer’s disease. The microtubule associated protein tau is abnormally phosphorylated and accumulates in these diseases, and we have established that the degradation machinery involved in tau metabolism may be a major contributor to this aberrant accretion. We are in the process of identifying other molecular chaperones that may be involved in tau biology, apart from those that we have already established. We are currently administering AAV constructs to our transgenic tau mouse model in an effort to determine the in vivo consequence of knockdown and over-expression of individual chaperones on tau pathology. We are also working with Dr. Henry Paulson at the University of Michigan on how these same mechanisms might be relevant for polyQ expansion diseases.
  • We are taking a more structural approach to investigating the relationship of tau with chaperones. We have begun using NMR as well as other biophysical techniques to investigate the binding of tau to specific chaperone proteins. We are using dynamic light scattering to investigate tau aggregation kinetics in the presence of chaperones, and we are working toward a technique to actually measure binding affinities of chaperones for tau. In collaboration with Dr. Hunt Potter here at USF, we have also developed a method to study the effects of chaperones on microtubule polymerization using Xenopus oocyte extracts. These molecular tools allow us to better understand the mechanisms of the tau/chaperone interface and how this might impact pathogenesis.
  • We have developed and utilized a cell-based drug screening process called the In-Cell Western, and in collaboration with Dr. Bill Baker, we have begun screening a novel library of extracts acquired from the Antarctic Ocean. Using extraction and mass spec technologies, we are able to identify specific compounds from these extracts once it has been determined that they reduce tau levels. We are working on several leads from these screens.
  • More recently, we have been exploring the role of chaperones in cancer biology. We have been developing compounds that can selectively target cancer cells through inhibition of the chaperone Hsp70. In addition we have found that these compounds may be able to overcome drug resistance that has developed in refractory breast cancer.
  • The program that I have established should be of great interest to the neurodegenerative disease and aging communities at large. These mechanisms may be relevant for other diseases of aging, including Parkinson’s, Huntington’s, amyolateral sclerosis and cancer. The turnover of abnormally modified or mutant proteins is critical in most diseases, and my hope is that the studies my team is leading will help to pave the way for future therapeutic development.

Memberships

  • American Society for Cell Biology (Member, 2007 - Present)
  • Society for Neuroscience (Member, 2002 - Present)
  • University of South Florida Alumni Association (Member, 1998 - Present)
  • Institute for Biomolecular Sciences (USF) (Member, 2000 - 2002)

Recent Publications

  • Evans, CG.Jinwal, UK.Makley, LN.Dickey, CA.Gestwicki, JE. Identification of dihydropyridines that reduce cellular tau levels. Chemical communications (Cambridge, England). 47(1) : 529-31, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21082080
  • Jinwal, UK.Dickey, CA. Cell-based assays for regulators of tau biology. Methods in molecular biology (Clifton, N.J.). 670: 93-108, 2011. http://www.ncbi.nlm.nih.gov/pubmed/20967586
  • Abisambra, JF.Blair, LJ.Hill, SE.Jones, JR.Kraft, C.Rogers, J.Koren, J.Jinwal, UK.Lawson, L.Johnson, AG.Wilcock, D.O'Leary, JC.Jansen-West, K.Muschol, M.Golde, TE.Weeber, EJ.Banko, J.Dickey, CA. Phosphorylation dynamics regulate Hsp27-mediated rescue of neuronal plasticity deficits in tau transgenic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(46) : 15374-82, 2010. http://www.ncbi.nlm.nih.gov/pubmed/21084594
  • Jinwal, UK.O'Leary, JC.Borysov, SI.Jones, JR.Li, Q.Koren, J.Abisambra, JF.Vestal, GD.Lawson, LY.Johnson, AG.Blair, LJ.Jin, Y.Miyata, Y.Gestwicki, JE.Dickey, CA. Hsc70 rapidly engages tau after microtubule destabilization. The Journal of biological chemistry. 285(22) : 16798-805, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20308058
  • Koren, J.Jinwal, UK.Jin, Y.O'Leary, J.Jones, JR.Johnson, AG.Blair, LJ.Abisambra, JF.Chang, L.Miyata, Y.Cheng, AM.Guo, J.Cheng, JQ.Gestwicki, JE.Dickey, CA. Facilitating Akt clearance via manipulation of Hsp70 activity and levels. The Journal of biological chemistry. 285(4) : 2498-505, 2010. http://www.ncbi.nlm.nih.gov/pubmed/19889640
  • Jones, JR.Lebar, MD.Jinwal, UK.Abisambra, JF.Koren, J.Blair, L.O'Leary, JC.Davey, Z.Trotter, J.Johnson, AG.Weeber, E.Eckman, CB.Baker, BJ.Dickey, CA. The Diarylheptanoid (+)-aR,11S-Myricanol and Two Flavones from Bayberry (Myrica cerifera) Destabilize the Microtubule-Associated Protein Tau. Journal of natural products. , 2010. http://www.ncbi.nlm.nih.gov/pubmed/21141876
  • Jinwal, UK.Koren, J.Borysov, SI.Schmid, AB.Abisambra, JF.Blair, LJ.Johnson, AG.Jones, JR.Shults, CL.O'Leary, JC.Jin, Y.Buchner, J.Cox, MB.Dickey, CA. The Hsp90 cochaperone, FKBP51, increases Tau stability and polymerizes microtubules. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(2) : 591-9, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20071522
  • Azorsa, DO.Robeson, RH.Frost, D.Meec hoovet, B.Brautigam, GR.Dickey, C.Beaudry, C.Basu, GD.Holz, DR.Hernandez, JA.Bisanz, KM.Gwinn, L.Grover, A.Rogers, J.Reiman, EM.Hutton, M.Stephan, DA.Mousses, S.Dunckley, T. High-content siRNA screening of the kinome identifies kinases involved in Alzheimer's disease-related tau hyperphosphorylation. BMC genomics. 11: 25, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20067632
  • Lee, DC.Rizer, J.Selenica, ML.Reid, P.Kraft, C.Johnson, A.Blair, L.Gordon, MN.Dickey, CA.Morgan, D. LPS- induced inflammation exacerbates phospho-tau pathology in rTg4510 mice. Journal of neuroinflammation. 7: 56, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20846376
  • Carty, N.Lee, D.Dickey, C.Ceballos-Diaz, C.Jansen-West, K.Golde, TE.Gordon, MN.Morgan, D.Nash, K. Convection-enhanced delivery and systemic mannitol increase gene product distribution of AAV vectors 5, 8, and 9 and increase gene product in the adult mouse brain. Journal of neuroscience methods. 194(1) : 144-53, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20951738
  • O'Leary, JC.Li, Q.Marinec, P.Blair, LJ.Congdon, EE.Johnson, AG.Jinwal, UK.Koren, J.Jones, JR.Kraft, C.Peters, M.Abisambra, JF.Duff, KE.Weeber, EJ.Gestwicki, JE.Dickey, CA. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Molecular neurodegeneration. 5: 45, 2010. http://www.ncbi.nlm.nih.gov/pubmed/21040568
  • Lebson, L.Nash, K.Kamath, S.Herber, D.Carty, N.Lee, DC.Li, Q.Szekeres, K.Jinwal, U.Koren, J.Dickey, CA.Gottschall, PE.Morgan, D.Gordon, MN. Trafficking CD11b-positive blood cells deliver therapeutic genes to the brain of amyloid-depositing transgenic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(29) : 9651-8, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20660248
  • Jinwal, UK.Koren, J.O'Leary, JC.Jones, JR.Abisambra, JF.Dickey, CA. Hsp70 ATPase Modulators as Therapeutics for Alzheimer's and other Neurodegenerative Diseases. Molecular and cellular pharmacology. 2(2) : 43-46, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20523917
  • Jinwal, UK.Miyata, Y.Koren, J.Jones, JR.Trotter, JH.Chang, L.O'Leary, J.Morgan, D.Lee, DC.Shults, CL.Rousaki, A.Weeber, EJ.Zuiderweg, ER.Gestwicki, JE.Dickey, CA. Chemical manipulation of hsp70 ATPase activity regulates tau stability. The Journal of neuroscience : the official journal of the Society for Neuroscience. 29(39) : 12079-88, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19793966
  • Dickey, C.Kraft, C.Jinwal, U.Koren, J.Johnson, A.Anderson, L.Lebson, L.Lee, D.Dickson, D.de Silva, R.Binder, LI.Morgan, D.Lewis, J. Aging analysis reveals slowed tau turnover and enhanced stress response in a mouse model of tauopathy. The American journal of pathology. 174(1) : 228-38, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19074615
  • Koren, J.Jinwal, UK.Lee, DC.Jones, JR.Shults, CL.Johnson, AG.Anderson, LJ.Dickey, CA. Chaperone signalling complexes in Alzheimer's disease. Journal of cellular and molecular medicine. 13(4) : 619-30, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19449461
  • Dickey, CA.Koren, J.Zhang, YJ.Xu, YF.Jinwal, UK.Birnbaum, MJ.Monks, B.Sun, M.Cheng, JQ.Patterson, C.Bailey, RM.Dunmore, J.Soresh, S.Leon, C.Morgan, D.Petrucelli, L. Akt and CHIP coregulate tau degradation through coordinated interactions. Proceedings of the National Academy of Sciences of the United States of America. 105(9) : 3622-7, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18292230
  • Zhang, YJ.Xu, YF.Dickey, CA.Buratti, E.Baralle, F.Bailey, R.Pickering-Brown, S.Dickson, D.Petrucelli, L. Progranulin mediates caspase-dependent cleavage of TAR DNA binding protein-43. The Journal of neuroscience : the official journal of the Society for Neuroscience. 27(39) : 10530-4, 2007. http://www.ncbi.nlm.nih.gov/pubmed/17898224
  • Dickey, CA.Kamal, A.Lundgren, K.Klosak, N.Bailey, RM.Dunmore, J.Ash, P.Shoraka, S.Zlatkovic, J.Eckman, CB.Patterson, C.Dickson, DW.Nahman, NS.Hutton, M.Burrows, F.Petrucelli, L. The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. The Journal of clinical investigation. 117(3) : 648-58, 2007. http://www.ncbi.nlm.nih.gov/pubmed/17304350
  • Dickey, CA.Patterson, C.Dickson, D.Petrucelli, L. Brain CHIP: removing the culprits in neurodegenerative disease. Trends in molecular medicine. 13(1) : 32-8, 2007. http://www.ncbi.nlm.nih.gov/pubmed/17127096
  • Baker, M.Mackenzie, IR.Pickering-Brown, SM.Gass, J.Rademakers, R.Lindholm, C.Snowden, J.Adamson, J.Sadovnick, AD.Rollinson, S.Cannon, A.Dwosh, E.Neary, D.Melquist, S.Richardson, A.Dickson, D.Berger, Z.Eriksen, J.Robinson, T.Zehr, C.Dickey, CA.Crook, R.McGowan, E.Mann, D.Boeve, B.Feldman, H.Hutton, M. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 442(7105) : 916-9, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16862116
  • Dickey, CA.Petrucelli, L. Current strategies for the treatment of Alzheimer's disease and other tauopathies. Expert opinion on therapeutic targets. 10(5) : 665-76, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16981824
  • Dickey, CA.Dunmore, J.Lu, B.Wang, JW.Lee, WC.Kamal, A.Burrows, F.Eckman, C.Hutton, M.Petrucelli, L. HSP induction mediates selective clearance of tau phosphorylated at proline-directed Ser/Thr sites but not KXGS (MARK) sites. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 20(6) : 753-5, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16464956
  • Lee, WC.Tsoi, YK.Dickey, CA.Delucia, MW.Dickson, DW.Eckman, CB. Suppression of galactosylceramidase (GALC) expression in the twitcher mouse model of globoid cell leukodystrophy (GLD) is caused by nonsense-mediated mRNA decay (NMD). Neurobiology of disease. 23(2) : 273-80, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16759875
  • Dickey, CA.Yue, M.Lin, WL.Dickson, DW.Dunmore, JH.Lee, WC.Zehr, C.West, G.Cao, S.Clark, AM.Caldwell, GA.Caldwell, KA.Eckman, C.Patterson, C.Hutton, M.Petrucelli, L. Deletion of the ubiquitin ligase CHIP leads to the accumulation, but not the aggregation, of both endogenous phospho- and caspase-3-cleaved tau species. The Journal of neuroscience : the official journal of the Society for Neuroscience. 26(26) : 6985-96, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16807328
  • Dickey, CA.Ash, P.Klosak, N.Lee, WC.Petrucelli, L.Hutton, M.Eckman, CB. Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. Molecular neurodegeneration. 1: 6, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16930453
  • Lee, WC.Courtenay, A.Troendle, FJ.Stallings-Mann, ML.Dickey, CA.DeLucia, MW.Dickson, DW.Eckman, CB. Enzyme replacement therapy results in substantial improvements in early clinical phenotype in a mouse model of globoid cell leukodystrophy. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 19(11) : 1549-51, 2005. http://www.ncbi.nlm.nih.gov/pubmed/15987783
  • Dickey, CA.Gordon, MN.Wilcock, DM.Herber, DL.Freeman, MJ.Morgan, D. Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice. BMC neuroscience. 6: 7, 2005. http://www.ncbi.nlm.nih.gov/pubmed/15689237
  • Dickey, CA.Eriksen, J.Kamal, A.Burrows, F.Kasibhatla, S.Eckman, CB.Hutton, M.Petrucelli, L. Development of a high throughput drug screening assay for the detection of changes in tau levels -- proof of concept with HSP90 inhibitors. Current Alzheimer research. 2(2) : 231-8, 2005. http://www.ncbi.nlm.nih.gov/pubmed/15974923
  • Dickey, CA.Gordon, MN.Mason, JE.Wilson, NJ.Diamond, DM.Guzowski, JF.Morgan, D. Amyloid suppresses induction of genes critical for memory consolidation in APP + PS1 transgenic mice. Journal of neurochemistry. 88(2) : 434-42, 2004. http://www.ncbi.nlm.nih.gov/pubmed/14690531
  • Garcia, MF.Gordon, MN.Hutton, M.Lewis, J.McGowan, E.Dickey, CA.Morgan, D.Arendash, GW. The retinal degeneration (rd) gene seriously impairs spatial cognitive performance in normal and Alzheimer's transgenic mice. Neuroreport. 15(1) : 73-7, 2004. http://www.ncbi.nlm.nih.gov/pubmed/15106834
  • Dickey, CA.De Mesquita, DD.Morgan, D.Pennypacker, KR. Induction of memory-associated immediate early genes by nerve growth factor in rat primary cortical neurons and differentiated mouse Neuro2A cells. Neuroscience letters. 366(1) : 10-4, 2004. http://www.ncbi.nlm.nih.gov/pubmed/15265580
  • Dickey, CA.Loring, JF.Montgomery, J.Gordon, MN.Eastman, PS.Morgan, D. Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 23(12) : 5219-26, 2003. http://www.ncbi.nlm.nih.gov/pubmed/12832546
  • Dickey, CA.Morgan, DG.Kudchodkar, S.Weiner, DB.Bai, Y.Cao, C.Gordon, MN.Ugen, KE. Duration and specificity of humoral immune responses in mice vaccinated with the Alzheimer's disease-associated beta-amyloid 1-42 peptide. DNA and cell biology. 20(11) : 723-9, 2001. http://www.ncbi.nlm.nih.gov/pubmed/11788050

Positions Held

  • Assistant Professor (Department of Molecular Pharmacology and Physiology, University of South Florida 2006 - 2008)
  • Senior Research Fellow (Department of Neuroscience, Mayo Clinic Jacksonville 2005 - 2006)
  • Research Fellow (Department of Neuroscience, Mayo Clinic 2004 - 2005)

Awards/Honors

  • Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease 2007)
  • Smith Award Recipient (Mayo Clinic Jacksonville - 2006)
  • ADRC Pilot Study Award Recipient 2006)
  • University of South Florida Department of Pharmacology Stipend Award (University of South Florida - 2004)
  • Institute for Biomolecular Sciences Competitive Stipend Award (University of South Florida - 2002)