Ph.D., Biochemistry, University of Queensland, 1996
B.S., Biochemistry and Microbiology, University of Queensland, 1991
Interdisciplinary and Emerging Signature Programs
Allergy, Immunology & Infectious Disease
Biomedical Engineering & Nanomedicine
Neurodegenerative Disease
Neuroscience
Research Interests
My research focus is now targeted towards using recombinant Adeno-associated virus (rAAV) to study of neurological disorders. 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.
Memberships
Member (The American Association for the Advancement of Science, 2008 - Present)
Member (American Society of Gene Therapy, 2008 - Present)
Member (Society for Neuroscience, 2008 - Present)
Recent Publications
Grimmig B, Kim SH, Nash K, Bickford PC, Douglas Shytle R. Neuroprotective mechanisms of astaxanthin: a potential therapeutic role in preserving cognitive function in age and neurodegeneration.GeroScience. 39(1) : 19-32, 2017.
Burger C, Nash KR. Small-Scale Recombinant Adeno-Associated Virus Purification.Methods in molecular biology (Clifton, N.J.). 1382: 95-106, 2016.
Nash KR, Gordon MN. Convection Enhanced Delivery of Recombinant Adeno-associated Virus into the Mouse Brain.Methods in molecular biology (Clifton, N.J.). 1382: 285-95, 2016.
Selenica MB, Reid P, Pena G, Alvarez J, Hunt JB, Nash KR, Morgan D, Gordon MN, Lee DC. Adeno associated viral-mediated intraosseous labeling of bone marrow derived cells for CNS tracking.Journal of immunological methods. , 2016.
Grimmig B, Morganti J, Nash K, Bickford PC. Immunomodulators as Therapeutic Agents in Mitigating the Progression of Parkinson''s Disease.Brain sciences. 6(4) , 2016.
Shahaduzzaman MD, Nash KR, Hudson C, Sharif M, Grimmig B, Lin X, Bai G, Liu H, Ugen KE, Cao C, & Bickford PC. Anti-human α-synuclein N-terminal peptide antibody protects against dopaminergic cell death and ameliorates behavioral deficits in an AAV-α-synuclein rat model of Parkinson’s DiseasePLoS One. 10(2) : e0116841, 2015.
Hunt JB, Nash KR, Placides D, Moran P, Selenica ML, Abuqalbeen F, Ratnasamy K, Slouha N, Rodriguez-Ospina S, Savlia M, Ranaweera Y, Reid P, Dickey CA, Uricia R, Yang CG, Sandusky LA, Gordon MN, Morgan D, Lee DC. Sustained Arginase 1 Expression Modulates Pathological Tau Deposits in a Mouse Model of Tauopathy.The Journal of neuroscience : the official journal of the Society for Neuroscience. 35(44) : 14842-60, 2015.
Nash KR, Moran P, Finneran DJ, Hudson C, Robinson J, Morgan D, Bickford PC. Fractalkine Over Expression Suppresses α-Synuclein-mediated Neurodegeneration.Molecular therapy : the journal of the American Society of Gene Therapy. , 2014.
Selenica ML, Benner L, Housley SB, Manchec B, Lee DC, Nash KR, Kalin J, Bergman JA, Kozikowski A, Gordon MN, Morgan D. Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition.Alzheimer''s research & therapy. 6(1) : 12, 2014.
Lee DC, Ruiz CR, Lebson L, Selenica ML, Rizer J, Hunt JB, Rojiani R, Reid P, Kammath S, Nash K, Dickey CA, Gordon M, Morgan D. Aging enhances classical activation but mitigates alternative activation in the central nervous system.Neurobiology of aging. 34(6) : 1610-20, 2013.
Carty N, Nash KR, Brownlow M, Cruite D, Wilcock D, Selenica ML, Lee DC, Gordon MN, Morgan D. Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice.PloS one. 8(3) : e59626, 2013.
Selenica ML, Alvarez JA, Nash KR, Lee DC, Cao C, Lin X, Reid P, Mouton PR, Morgan D, Gordon MN. Diverse activation of microglia by chemokine (C-C motif) ligand 2 overexpression in brain.Journal of neuroinflammation. 10: 86, 2013.
Nash KR, Lee DC, Hunt JB, Morganti JM, Selenica ML, Moran P, Reid P, Brownlow M, Guang-Yu Yang C, Savalia M, Gemma C, Bickford PC, Gordon MN, Morgan D. Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy.Neurobiology of aging. 34(6) : 1540-8, 2013.
Morganti JM, Nash KR, Grimmig BA, Ranjit S, Small B, Bickford PC, Gemma C. The soluble isoform of CX3CL1 is necessary for neuroprotection in a mouse model of Parkinson''s disease.The Journal of Neuroscience : the official journal of the Society for Neuroscience. 32(42) : 14592-601, 2012.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Burger C, Nash K, Mandel RJ. Recombinant adeno-associated viral vectors in the nervous system.Human gene therapy. 16(7) : 781-91, 2005.
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.
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.
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.
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.
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.
Positions Held
Research Assistant Professor (Powell Centre for Gene Therapy, University of Florida 2002 - 2007)
