John Olsen
Research Associate Professor
of Medicine
Degrees
BS:
(1974) Oregon State U.
Corvallis OR
PhD:
(1982) U. of Montana.
Missoula MT
Post-Doctoral:
(1990) U. of North Carolina
Chapel Hill NC
Office:
7103 Thurston-Bowles
Phone: 919-966-6768
Fax: 919-966-5178
email:
olyunc@med.unc.edu
Research Interests:
- Gene transfer using retroviruses and lentiviruses.
- Regulation of gene expression.
- Gene therapy for cystic fibrosis and other diseases.
Purpose of Research
An important prospect for future treatment of CF lung disease is the development of viral vectors for gene therapy. Dr. John Olsen has
developed a novel lentiviral-based gene delivery system based upon equineinfectious anemia virus (EIAV) that can efficiently transfer
genes to human cells. The main advantage of EIAV-based vectors over conventional retroviral vectors is that EIAV vectors transfer and express genes
in non-dividing cells as well as dividing cells. Thus, these vectors will have utility in transferring genes to slowly growing cells of the respiratory epithelium. The overall goals of Dr. Olsen's lab are two-fold. First, to study fundamental aspects of lentiviral vector biology in order to
optimize gene transfer efficiency and expression. This will allow the manipulation of the vector system to achieve safe and efficient use in the clinic. Second, to use the knowledge of lentiviral vector biology in an applied sense, to address issues important for treatment of specific diseases. Recent progress has been made in the identification and characterization of the EIAV RNA encapsidation signal. This has led to strategies for the design of more efficient gene transfer vectors and has allowed the development of stable packaging cell lines for the safe and efficient production of EIAV vectors. Progress has also been made in developing viral vector technology for more efficient gene transfer to the tracheal epithelium of young mice.
Recent Publications:
1999-2000 pulications/submissions
Wilcox DA, Olsen JC, Ishizawa L, Griffith M, and White II GC (1999) Integrin alpha IIb promoter-targeted expression of gene products in megakaryocytes derived from retrovirus-transduced human hematopoietic cells. Proc Natl Acad Sci USA 96: 9654-9659.
Johnson, LG, Olsen JC, Naldini L, and Boucher RC (2000) Pseudotyped human lentiviral vector-mediated gene transfer to polarized differentiatedairway epithelia. Gene Therapy 7: 568-574.
Ly, H, Nierlich, DP, Olsen, JC, and Kaplan, AH (1999) Moloney murinesarcoma virus genomic RNAs dimerize via a two-step process: A concentration-dependent kissing-loop interaction is driven by initial contact between consecutive guanines. J Virol 73 7255-7261.
Wilcox DA, Olsen JC, Ishizawa L, Bray PF, French DL, Steeber DA, Bell WR, Griffith M, and White II GC (2000) Megakaryocyte-targeted synthesis of the integrin beta(3)-subunit results in the phenotypic correction of Glanzmann thrombasthenia. Blood, 95: 3645-3651.
Yamada, K, Olsen, JC, Patel, M, Rao, KW, and Walsh, CE (2001) Functional correction of Fanconi anemia group C (FANCC) hematopoietic cells by the use of a novel lentiviral vector. Molecular Therapy April 2001; 3(4):485-490.
Olsen JC. EIAV, CAEV and other lentivirus vector systems. Somat Cell Mol Genet. Nov 2001;26(1-6):131-145.
O'Rourke JP, Newbound GC, Kohn DB, Olsen JC, Bunnell BA. Comparison of gene transfer efficiencies and gene expression levels achieved with equine infectious anemia virus- and human immunodeficiency virus type 1-derived lentivirus vectors. J Virol. Feb 2002;76(3):1510-1515.
Schnabl B, Choi YH, Olsen JC, Hagedorn CH, Brenner DA. Immortal activated human hepatic stellate cells generated by ectopic telomerase expression. Lab Invest. Mar 2002;82(3):323-333.
Lundberg AS, Randell SH, Stewart SA, Elenbaas B, Hartwell KA, Brooks MW, Fleming MD, Olsen JC, Miller SW, Weinberg RA, Hahn WC. Immortalization and transformation of primary human airway epithelial cells by gene transfer. Oncogene. Jul 4 2002 ;21(29):4577-4586.
Tarran R, Loewen ME, Paradiso AM, Olsen JC, Gray MA, Argent BE, Boucher RC. Regulation of murine airway surface liquid volume by CFTR and Ca(2+)-activated Cl(-) conductances. J Gen Physiol 2002; 120: 407-418.
O'Rourke JP, Hiraragi H, Urban K, Patel M, Olsen JC, Bunnell BA. Analysis of gene transfer and expression in skeletal muscle using enhanced EIAV lentivirus vectors. Mol Ther 2003; 7: 632-639.
Schoch KG, Lori A, Burns KA, Eldred T, Olsen JC, and Randell SH. A subset of mouse tracheal epithelial basal cells generates large colonies in vitro. Am J Physiol Lung Cell Mol Physiol 2004; 286: L631-642.
Ehre C, Rossi AH, Abdullah LH, De Pestel K, Hill S, Olsen JC, and Davis CW. Barrier Role of Actin Filaments in Regulated Mucin Secretion from Airway Goblet Cells. Am J Physiol Cell Physiol . 2005; 288: C46-56
O'Rourke JP, Olsen JC, and Bunnell, BA. Optimization of equine infectious anemia derived vectors for hematopoietic cell lineage gene transfer. Gene Ther 2005; 12: 22-299
Kingsman SM, Mitrophanous K, and Olsen JC. Potential oncogene activity of the woodchuck hepatitis post-transcriptional regulatory element (WPRE). Gene Ther 2005; 12: 3-4
McKay T, Patel M, Pickles RJ, Johnson LG, Olsen JC. Influenza M2 envelope protein augments hemagglutinin pseudotyping of lentiviral vectors. Gene Ther 2005; Submitted
Book Chapters:
Comstock KE, Watson NF , Olsen JC. Design of retroviral expression vectors. In: Tuan R, ed. Methods in Molecular Biology, vol. 62: Recombinant Gene Expression Protocols . Totowa , NJ : Humana Press Inc.; 1997:207-222.
Olsen JC, Johnson LG, Yankaskas JR. Methods for use of retroviral vectors for transfer of the CFTR gene to airway epithelium. In: Robbins P, ed. Methods in Molecular Medicine: Gene Therapy Protocols . Totowa , NJ : Humana Press Inc.; 1997.
Morse K, Olsen JC. An ecdysone-inducible expression system for use with retroviruses. In: Machida CA , ed. Methods in Molecular Medicine, vol.76: Viral Vectors for Gene Therapy: Methods and Protocols . Totowa , NJ : Humana Press Inc.; 2003:331-342.
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