My Profile
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Kevin Nash
, Ph.D.
Primary Department: COLLEGE OF MEDICINE MOLECULAR PHARMACOLOGY & PHYSIOLOGY
Assistant Professor COLLEGE OF MEDICINE MOLECULAR PHARMACOLOGY & PHYSIOLOGY
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| Contacts |
| Email: |
knash@health.usf.edu
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| Phone: |
(813) 974-3788 |
| Office: |
ALZ, 421 |
| Mailing address |
12901 Bruce B. Downs Blvd. ,MDC 8
Tampa, FL 33612
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View My C.V. |
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Education |
| Ph.D. , Biochemistry, University of Queensland , Queensland, Australia - 1996. |
| B.S., Biochemistry and Microbiology, University of Queensland , Queensland, Australia - 1991. |
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Interdisciplinary & Emerging Signature Programs |
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Research Summary |
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My research focus is now targeted towards using recombinant Adeno-associated virus (rAAV) to study of neurological disorders. rAAV has gained attention as an excellent gene therapy vehicle for the central nervous system. Features that make AAV an attractive tool for the treatment of neurological disorders and for the study of the nervous system include the fact that the wild-type virus is non-pathogenic, it has low immunogenicity, all viral genes are removed from the recombinant virus, long term expression is attainable and the virus can infects neurons efficiently. We have examined the use of rAAV to over express proteases including neprilysin (NEP), insulin degrading enzyme (IDE; also known as insulysin) and endothelin converting enzyme (ECE) to remove beta-amyloid which is deposited in Alzhiemer disease. To facilitate the diffusion of the protease enzymes to the amyloid plaques, we have engineered the proteins with a signal peptide triggering secretion. We have successfully observed a reduction in amyloid plaques with both NEP and ECE in APP+PS1 transgenic Alzheimer mice models. We are also using rAAV to study an inflammatory molecule known as Fractalkine. Fractalkine reduces the pro-inflammatory response that is observed in many neurological diseases. We are examining whether this reduction in inflammation would be beneficial in Alzheimer and Parkinson’s diseases. |
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Selected Publications
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Nash, K.Feldmuller, M.de Jersey, J.Alewood, P.Hamilton, S.
Continuous and discontinuous assays for phosphotyrosyl protein phosphatase activity using phosphotyrosyl peptide substrates.
Analytical biochemistry. 213(2): 303-9, 1993.
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Marshall, K.Nash, K.Haussman, G.Cassady, I.Hume, D.de Jersey, J.Hamilton, S.
Recombinant human and mouse purple acid phosphatases: expression and characterization.
Archives of biochemistry and biophysics. 345(2): 230-6, 1997.
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Dunn, BM.Pennington, MW.Frase, DC.Nash, K.
Comparison of inhibitor binding to feline and human immunodeficiency virus proteases: structure-based drug design and the resistance problem.
Biopolymers. 51(1): 69-77, 1999.
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Valizadeh, M.Schenk, G.Nash, K.Oddie, GW.Guddat, LW.Hume, DA.de Jersey, J.Burke, TR.Hamilton, S.
Phosphotyrosyl peptides and analogues as substrates and inhibitors of purple acid phosphatases.
Archives of biochemistry and biophysics. 424(2): 154-62, 2004.
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Burger, C.Nash, K.Mandel, RJ.
Recombinant adeno-associated viral vectors in the nervous system.
Human gene therapy. 16(7): 781-91, 2005.
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Rodriguez-Lebron, E.Denovan-Wright, EM.Nash, K.Lewin, AS.Mandel, RJ.
Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic mice.
Molecular therapy : the journal of the American Society of Gene Therapy. 12(4): 618-33, 2005.
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Kohlbrenner, E.Aslanidi, G.Nash, K.Shklyaev, S.Campbell-Thompson, M.Byrne, BJ.Snyder, RO.Muzyczka, N.Warrington, KH.Zolotukhin, S.
Successful production of pseudotyped rAAV vectors using a modified baculovirus expression system.
Molecular therapy : the journal of the American Society of Gene Therapy. 12(6): 1217-25, 2005.
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Mandel, RJ.Manfredsson, FP.Foust, KD.Rising, A.Reimsnider, S.Nash, K.Burger, C.
Recombinant adeno-associated viral vectors as therapeutic agents to treat neurological disorders.
Molecular therapy : the journal of the American Society of Gene Therapy. 13(3): 463-83, 2006.
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Nash, K.Chen, W.McDonald, WF.Zhou, X.Muzyczka, N.
Purification of host cell enzymes involved in adeno-associated virus DNA replication.
Journal of virology. 81(11): 5777-87, 2007.
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Carty, NC.Nash, K.Lee, D.Mercer, M.Gottschall, PE.Meyers, C.Muzyczka, N.Gordon, MN.Morgan, D.
Adeno-associated viral (AAV) serotype 5 vector mediated gene delivery of endothelin-converting enzyme reduces Abeta deposits in APP + PS1 transgenic mice.
Molecular therapy : the journal of the American Society of Gene Therapy. 16(9): 1580-6, 2008.
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Nash, K.Chen, W.Muzyczka, N.
Complete in vitro reconstitution of adeno-associated virus DNA replication requires the minichromosome maintenance complex proteins.
Journal of virology. 82(3): 1458-64, 2008.
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Nash, K.Chen, W.Salganik, M.Muzyczka, N.
Identification of cellular proteins that interact with the adeno-associated virus rep protein.
Journal of virology. 83(1): 454-69, 2009.
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Levy, HC.Bowman, VD.Govindasamy, L.McKenna, R.Nash, K.Warrington, K.Chen, W.Muzyczka, N.Yan, X.Baker, TS.Agbandje-McKenna, M.
Heparin binding induces conformational changes in Adeno-associated virus serotype 2.
Journal of structural biology. 165(3): 146-56, 2009.
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Choi, YK.Nash, K.Byrne, BJ.Muzyczka, N.Song, S.
The effect of DNA-dependent protein kinase on adeno-associated virus replication.
PloS one. 5(12): e15073, 2010.
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Galleguillos, D.Fuentealba, JA.Gómez, LM.Saver, M.Gómez, A.Nash, K.Burger, C.Gysling, K.Andrés, ME.
Nurr1 regulates RET expression in dopamine neurons of adult rat midbrain.
Journal of neurochemistry. 114(4): 1158-67, 2010.
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Gorbatyuk, OS.Li, S.Nash, K.Gorbatyuk, M.Lewin, AS.Sullivan, LF.Mandel, RJ.Chen, W.Meyers, C.Manfredsson, FP.Muzyczka, N.
In vivo RNAi-mediated alpha-synuclein silencing induces nigrostriatal degeneration.
Molecular therapy : the journal of the American Society of Gene Therapy. 18(8): 1450-7, 2010.
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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.
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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.
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Daily, JL.Nash, K.Jinwal, U.Golde, T.Rogers, J.Peters, MM.Burdine, RD.Dickey, C.Banko, JL.Weeber, EJ.
Adeno-associated virus-mediated rescue of the cognitive defects in a mouse model for Angelman syndrome.
PloS one. 6(12): e27221, 2011.
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Nash, KR.Cardenas-Aguayo, MC.Berg, MJ.Marks, N.
Transduction of E13 murine neural precursor cells by non-immunogenic recombinant adeno-associated viruses induces major changes in neuronal phenotype.
Neuroscience. 210(): 82-98, 2012.
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Li, Q.Lebson, L.Lee, DC.Nash, K.Grimm, J.Rosenthal, A.Selenica, ML.Morgan, D.Gordon, MN.
Chronological age impacts immunotherapy and monocyte uptake independent of amyloid load.
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 7(1): 202-14, 2012.
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Positions Held
- Assistant Professor
(Dept. of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida 2008 -
Present)
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- Research Assistant Professor
(Powell Centre for Gene Therapy, University of Florida 2002 -
2007)
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Memberships
- The American Association for the Advancement of Science
(Member,
2008 -
Present)
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- Society for Neuroscience
(Member,
2008 -
Present)
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- American Society of Gene Therapy
(Member,
2008 -
Present)
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Patents & Licensing
- Pseudotyping of recombinant AAV verions (Snyder et al.) Patent pending
(US Application No. 60/385,864 - 2008)
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Grants
- MODULATION OF MICROGLIAL ACTIVATION
($125,000.00,
06/01/2011-05/31/2013)
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- MODULATION OF MICROGLIAL ACTIVATION
($125,000.00,
06/01/2011-05/31/2013)
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Profile last modified on 01/07/2013
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