Douglas M. McCarty, Ph.D. :: Nationwide Children's Hospital, Columbus, Ohio

Douglas M. McCarty, PhD

Douglas M. McCarty, PhD

Center for Gene Therapy
Principal Investigator

Neurology
Principal Investigator

Neurology Residency
Faculty

Neuromuscular Disorders
Principal Investigator

Contact Information

The Research Institute at Nationwide Children's Hospital
700 Childrens Drive
Columbus, OH 43205 [ map ]
PH: (614) 722-2875
FX: (614) 722-3273
E-mail Me

Biography

Gender:

  • Male

Languages Spoken:

  • English

Research Interests

Research Center:

Areas of Interest:

  • Our laboratory focuses on the development and application of adeno-associated virus (AAV) as a delivery vector for gene therapy. Our primary application for these vectors is the treatment of monogenetic lysosomal storage diseases, particularly mucopolysaccharidosis types IIIA and IIIB. These diseases are characterized by progressive neurodegneration beginning in early childhood. This necessitates effective gene delivery to the brain, which we approach by intravenous injection of an AAV serotype that crosses the blood-brain-barrier. We are also addressing the safety of AAV gene therapy in terms of the potential risk of cancer due to insertion of the vector genome into recipient cell chromosomes. This work involves the characterization of interactions between the AAV genome and the cellular DNA repair system, as well as long term tumor studies in mice. We are currently beginning a study to determine which features of the AAV genome are most likely to contribute to tumorigenesis.

Education and Training

Undergraduate School

  • West Virginia University
    Date Completed: 06/30/1978

Post Doctoral

  • University of Florida
    Date Completed: 06/30/1987

Fellowship

  • State University of New York
    Date Completed: 06/30/1994

Professional Experience

2009–present

  • Associate Professor of Pediatrics, Department of Pediatrics, The Research Institute at Nationwide Children's Hospital, and the Ohio State University, Columbus, OH

2004–present

  • Assistant Professor, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University

1997–2004

  • Research Assistant Professor, Division of Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill

1994–1997

  • Vector Core Facility Director, Gene Therapy Center, University of North Carolina at Chapel Hill

1987–1993

  • Postdoctoral Fellow, Departmet of Microbiology, State University of New York at Stony Brook

Publications

  • Rosas,Lucia,E; Grieves,Jessica,L; Zaraspe,Kimberly; La Perle,Krista,MD; Fu,Haiyan; McCarty,Douglas,M. 2012. Patterns of scAAV Vector Insertion Associated With Oncogenic Events in a Mouse Model for Genotoxicity.  MOLECULAR THERAPY. Vol. 20, no. 11. (November): 2098-2110.
  • Fu H, Bartz JD, Stephens RL Jr, McCarty DM. 2012. Peripheral nervous system neuropathology and progressive sensory impairments in a mouse model of Mucopolysaccharidosis IIIB.  PLoS One. Vol. 7, no. 9. (September): ee45992.
  • Fu,Haiyan; DiRosario,Julianne; Killedar,Smruti; Zaraspe,Kimberly; McCarty,Douglas,M. 2011. Correction of Neurological Disease of Mucopolysaccharidosis IIIB in Adult Mice by rAAV9 Trans-Blood-Brain Barrier Gene Delivery.  MOLECULAR THERAPY. Vol. 19, no. 6. (June): 1025-1033.
  • Fu H, Dirosario J, Killedar S, Zaraspe K, McCarty DM. 2011. Correction of Neurological Disease of Mucopolysaccharidosis IIIB in Adult Mice by rAAV9 Trans-Blood-Brain Barrier Gene Delivery.  Molecular Therapy. Vol. 19, no. 6. (June): 1025-1033.
  • McCarty,Douglas,M; DiRosario,Julianne; Gulaid,Kadra; Killedar,Smruti; Oosterhof,Arie; van Kuppevelt,Toin,H; Martin,Paul,T; Fu,Haiyan. 2011. Differential distribution of heparan sulfate glycoforms and elevated expression of heparan sulfate biosynthetic enzyme genes in the brain of mucopolysaccharidosis IIIB mice.  METABOLIC BRAIN DISEASE. Vol. 26, no. 1. (March): 9-19.
  • McCarty DM, DiRosario J, Gulaid K, Killedar S, Oosterhof A, van Kuppevelt TH, Martin PT, Fu H. 2011. Differential distribution of heparan sulfate glycoforms and elevated expression of heparan sulfate biosynthetic enzyme genes in the brain of mucopolysaccharidosis IIIB mice.  Metabolic Brain Disease. Vol. 26, no. 1. (March): 9-19.
  • Cataldi MP, McCarty DM. 2010. Differential effects of DNA double-strand break repair pathways on single-strand and self-complementary adeno-associated virus vector genomes.  Journal of Virology. Vol. 84, no. 17. (September): 8673-8682.
  • Fu,Haiyan; DiRosario,Julianne; Kang,Lu; Muenzer,Joseph; McCarty,Douglas,M. 2010. Restoration of central nervous system alpha-N-acetylglucosaminidase activity and therapeutic benefits in mucopolysaccharidosis IIIB mice by a single intracisternal recombinant adeno-associated viral type 2 vector delivery.  JOURNAL OF GENE MEDICINE. Vol. 12, no. 7. (July): 624-633.
  • Fu H, DiRosario J, Kang L, Muenzer J, McCarty DM. 2010. Restoration of central nervous system alpha-N-acetylglucosaminidase activity and therapeutic benefits in mucopolysaccharidosis IIIB mice by a single intracisternal recombinant adeno-associated viral type 2 vector delivery.  Journal of Gene Medicine. Vol. 12, no. 7. (July): 624-633.
  • Killedar S, Dirosario J, Divers E, Popovich PG, McCarty DM, Fu H. 2010. Mucopolysaccharidosis IIIB, a lysosomal storage disease, triggers a pathogenic CNS autoimmune response.  Journal of Neuroinflammation. Vol. 7, no. 39. (July).
  • McCarty, D.M., Dirosario, J., Gulaid, K., Muenzer, J., and Fu, H. 2009. Mannitol-facilitated CNS entry of rAAV2 vector significantly delayed the neurological disease progression in MPS IIIB mice.  Gene Therapy.
  • DiRosario,Julianne; Divers,Erin; Wang,Chuansong; Etter,Jonathan; Charrier,Alyssa; Jukkola,Peter; Auer,Herbert; Best,Victoria; Newsom,David,L; McCarty,Douglas,M; Fu,Haiyan. 2009. Innate and Adaptive Immune Activation in the Brain of MPS IIIB Mouse Model.  JOURNAL OF NEUROSCIENCE RESEARCH. Vol. 87, no. 4. (March): 978-990.
  • Dirosario, J., Divers, E., Wang, C., Etter, J., Charrier, A., Jukkola, P., Auer, H., Best, V., Newsom, D.L., McCarty, D.M., Fu, H. 2009. Innate and adaptive immune activation in the brain of MPS IIIB mouse model.  J Neurosci Res..
  • McCarty, D.M. 2008. Self-complementary AAV vectors; advances and applications.  Mol Ther.. Vol. 16, no. 10. (October): 1648-1656.
  • Fu,H; Kang,L; Jennings,J,S; Moy,S,S; Perez,A; DiRosario,J; McCarty,D,M; Muenzer,J. 2007. Significantly increased lifespan and improved behavioral performances by rAAV gene delivery in adult mucopolysaccharidosis IIIB mice.  GENE THERAPY. Vol. 14, no. 14. (July): 1065-1077.
  • Fu, H., Kang, L., Jennings, J.S., Moy, S.S., Perez, A., Dirosario, J., McCarty, D.M., Muenzer, J. 2007. Significantly increased lifespan and improved behavioral performances by rAAV gene delivery in adult mucopolysaccharidosis IIIB mice.  Gene Therapy. Vol. 14, no. 14. (January): 1065-1077.
  • Choi, V.W., McCarty, D.M., and Samulski, R.J. 2006. Host cell DNA repair pathways in adeno-associated viral genome processing.  J Virol. Vol. 80, no. 21. (November): 10346-56.
  • Storek, B., Harder, N.M., Banck, M.S., Wang, C., McCarty D.M., Janssen, W.G., Morrison, J.H., Walsh, C.E., and Beutler, A.S. 2006. Intrathecal long-term gene expression by self-complementary adeno-associated virus type 1 suitable for chronic pain studies in rats.  Mol. Pain. Vol. 2, no. 1. (January): e4.
  • Hacker, U.T., Wingenfeld, L., Kofler, D.M., Schuhmann, N.K., Lutz, S., Herold, T., King, S.B., Gerner, F.M., Perabo, L., Rabinowitz, J., McCarty, D.M., Samulski, R.J., Hallek, M., and Buning, H. 2005. Adeno-associated virus serotypes 1 to 5 mediated tumor cell directed gene transfer and improvement of transduction efficiency.  J Gene Med.. Vol. 7, no. 11. (November): 1429-38.
  • Choi, V.W., McCarty, D.M., and Samulski, R.J. 2005. AAV hybrid serotypes: improved vectors for gene delivery.  Curr Gene Ther. Vol. 5, no. 3. (June): 299-310.
  • Choi, V.W., Samulski, R.J., and McCarty, D.M. 2005. Effects of adeno-associated virus DNA hairpin structure on recombination.  J Virol. Vol. 79, no. 11. (June): 6801-7.
  • Xu, D., McCarty, D.M., Fernandes, A., Fisher, M., Saulski, R.J., and Juliano, R.L. 2005. Delivery of MDR1 small interfering RNA by self-complementary recombinant adeno-associated virus vector.  Mol Ther.. Vol. 11, no. 4. (April): 523-30.
  • McCarty,D,M; Young,S,M; Samulski,R,J. 2004. Integration of adeno-associated virus (AAV) and recombinant AAV vectors.  ANNUAL REVIEW OF GENETICS. Vol. 38, no. January: 819-845.
  • Negishi, A., Chen, J., McCarty, D.M., Samulski, R.J., Liu, J., and Superfine, R. 2004. Analysis of the interaction between adeno-associated virus and heparan sulfate using atomic force microscopy.  Glycobiology.
  • McCarty, D.M., Young Jr, S.M., and Samulski, R.J. 2004. Integration of Adeno-Associated Virus (AAV) and Recombinant AAV Vectors. In Annual Review of Genetics. Edited by Allan Campbell. Palo Alto, CA: Annual Reviews.
  • Amis, T.J., McCarty, D.M., Skulimowski, A. and Samulski, R.J. 2003. Identification and characterization of an adeno-associated virus integration site in CV-1 cells from the African green monkey.  J Virol. Vol. 77, no. 3. (January): 1904-15.
  • Yamada, K., McCarty, D.M., Madden, V.J., and Walsh, C.E. 2003. Lentivirus vector purification using anion exchange HPCL leads to improved gene transfer.  Biotechniques 2003. Vol. 34, no. 5. (January): 1074-8.
  • Stilwell, J.L., McCarty, D.M., Negishi, A., Superfine, R., and Samulski, R.J. 2003. Development and characterization of novel empty adenovirus capsids and their impact on celllular gene expression.  J Virol 2003,. Vol. 77, no. 23. (January): 12881-5.
  • Fu, H., Muenzer, J., Samulski, R.J., Breese, G., Sifford, J., Zeng, X., and McCarty, D.M. 2003. Self-complementary adeno-associated virus serotype 2 vector: global distribution and broad dispersion of AAV-mediated transgene expression in mouse brain.  Mol Ther 2003. Vol. 8, no. 6. (January): 911-7.
  • McCarty, F.M., Fu, H., Monahan, P.E., Toulson, C.E., Naik, P., and Samulski, R.J. 2003. Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo.  Gene Ter 2003. Vol. 10, no. 26. (January): 2112-8.
  • McCarty, D.M., Monahan, P.E., and Samulski, R.J. 2001. Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis.  Gene Ther. Vol. 8, no. 16. (August): 1248-54.
  • Wheeler, M.D., Kono, H., Rusyn, I., Arteel, G.E., McCarty, D.M., Samulski, R.J., and Thurman, R.G. 2000. Chronic ethanol increases adeno-associated viral transgene expression in rat liver via oxidant and NFkappaB-dependent mechanisms.  Hepatology. Vol. 32, no. 5. (November): 1050-9.
  • Young, S.M. Jr., McCarty, D.M., Degtyareva N., and Samulski, R.J. 2000. Roles of adeno-associated virus Rep protein and human chromosome 19 in site-specific recombination.  J Virol. Vol. 74, no. 9. (January): 3953-66.
  • Chen, H., McCarty, D.M., Bruce, A.T., and Suzuki, K. 1999. Oligodendrocyte-specific gene expression in mouse brain: use of a myelin-forming cell type-specific promoter in an adeno-associated virus.  J Neurosci Res. Vol. 55, no. 4. (February): 504-13.
  • Teramoto, S., Bartlett, J.S., McCarty, D.M., Xiao, X., Samulski, R.J., and Boucher, R.C. 1998. Factors influencing adeno-associated virus-mediated gene transfer to human cystic fibrosis airway epithelial cells: comparision with adenovirus vectors.  J Virol. Vol. 72, no. 11. (November): 8904-12.
  • Pickles, R.J., McCarty D.M., Matsui, H., Hart, P.J., Randell, S.H., and Boucher, R.C. 1998. Limited entry of adenovirus vectors into well-differentiated airway epithelium is responsible for inefficient gene transfer.  J. Virol. Vol. 72, no. 7. (July): 6014-23.
  • Chen, H., McCarty, D.M., Bruce, A.T., Suzuki, K., and Suzuki, K. 1998. Gene transfer and expression in oligodendrocytes under the control of myelin basic protein transcriptional control region mediated by adeno-associated virus.  Gene Ther. Vol. 5, no. 1. (January): 50-8.
  • Ferrari,F,K; Xiao,X; McCarty,D; Samulski,R,J. 1997. New developments in the generation of Ad-free, high-titer rAAV gene therapy vectors.  NATURE MEDICINE. Vol. 3, no. 11. (November): 1295-1297.
  • Piedimonte, G., Pickles, R.J., Lehmann, J.R., McCarty, D.M., Costa, D.L., and Boucher, R.C. 1997. Replication-deficient adenoviral vector for gene transfer potentiates airway neurogenic inflammation.  Am J Respir Cell Mol Biol. Vol. 16, no. 3. (March): 250-8.
  • Ferrarai, F.K., Xiao, X., McCarty, D.M., and Samulski, R.J. 1997. New developments in the generation of Ad-free, high-titer rAAV gene therapy vectors.  Nat Med. Vol. 3, no. 11. (March): 1295-7.
  • Pereira, D.J., McCarty, D.M., and Muzyczk, N. 1997. The adeno-associated virus (AAV) Rep protein acts as both a repressor and an activator to regulate AAV transcription during a productive infection.  J Virol. Vol. 71, no. 2. (February): 1079-88.
  • McCarty, D.M., and Samulski, R.J. 1997. Adeno-Associated Viral Vectors. In Concepts in Gene Therapy. Edited by M. Strauss and J.A. Barranger. Berlin: Walter de Gruyter.
  • McCarty, D.M., and Samulski, R.J. 1996. Adeno-Associated virus vectors for gene transfer into erythroid cells. In Adeno-Associated Virus (AAV) Vectors in Gene Therapy. Edited by K.I. Berns and C. Giraud. Berlin: Springer.
  • McCarty,D,M; Samulski,R,J. 1996. Adeno-associated virus vectors for gene transfer into erythroid cells.  ADENO-ASSOCIATED VIRUS (AAV) VECTORS IN GENE THERAPY. Vol. 218, no. January: 75-91.
  • McCarty D.M., Pereira, D.J., Zolotukhin, I., Zhou, X., Ryan, J.H., and Muzyczka, N. 1994. Identification of linear DNA sequences that specifically bind the adeno-associated virus Rep protein.  J Virol. Vol. 68, no. 8. (August): 4988-97.
  • McCarty, D.M., Ryan, J.H., Zolotukhin, S., Zhou, X., and Muzyczka, N. 1994. Interaction of the adeno-associated virus Rep protein with a sequence within the A palindrome of the viral terminal repeat.  J Virol. Vol. 68, no. 8. (August): 4998-5006.
  • Ni, T.H., Zhou, X., McCarty, D.M., Zolotukhin, I., and Muzyczka, N. 1994. In vitro replication of adeno-associated virus DNA.  J virol. Vol. 68, no. 2. (February): 1128-38.
  • McCarty, D.M., Ni, T.H., and Muzyczka, N. 1992. Analysis of mutations in adeno-associated virus Rep protein in vivo and in vitro.  J Virol. Vol. 66, no. 7. (July): 4050-7.
  • McCarty, D.M., Christensen, M., and Muzyczka, N. 1991. Sequences required for coordinate induction of adeno-associated virus p19 and p40 promoters by Rep protein.  J Virol. Vol. 65, no. 6. (June): 2936-45.
  • McCarty, D.M., Hehman, G.L., and Hauswirth, W.W. 1988. Nucleotide sequence of the Zea mays mitochondrial cytochrome oxidase subunit III gene.  Nucleic Acids Res. Vol. 16, no. 20. (October): e9873.
  • Fejes, E., Masters, B.S., McCarty, D.M., and Hauswirth, W.W. 1988. Sequences and transcriptional analysis of a chloroplast insert in the mitochrondrial genome of Zea mays.  Curr Genet. Vol. 13, no. 6. (June): 509-15.
  • Masters, B.S., McCarty, D.M., and Hauswirth, W.W. 1983. Gel Analysis of Plant Mitochondrial RNA.  Plant Molecular Biology Reporter. Vol. 1, no. January: 125-130.
  • Cataldi MP, McCarty DM. Hairpin-end conformation of adeno-associated virus genome determines interactions with DNA-repair pathways.  Gene Therapy.
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