Research Interests
Dr. Wilson’s laboratory focuses on the development of gene transfer vectors and their application in the treatment of a variety of acquired and inherited diseases. He has recently isolated new families of simian-based adenoviruses and adeno-associated viruses. Characterization of these new isolates has yielded important insights into basic virology. More importantly, recombinant versions of these viruses have shown to be useful as improved gene transfer vehicles to a variety of targets. These studies have included gene transfer to lung for the treatment of CF and to liver for the treatment of inherited dyslipidemias. Another major effort is the development of genetic vaccines against a number of biologic weapons and emerging infections such as Ebola virus and the SARS coronavirus.
Key words: adenovirus, adeno-associated virus (AAV), gene therapy, gene transfer, lentivirus.
Description of Research
Dr. Wilson is interested in the study of inherited diseases and the development of effective therapies. One theme is the evaluation of cell biology relevant to organs affected in inherited diseases such as the lung in cystic fibrosis, the muscle in inherited muscular dystrophies and the liver in inborne errors of metabolism. Dr. Wilson’s group uses animal models to evaluate the regenerative capacity of these organs as well as the existence of stem cells. In characterizing cystic fibrosis, Dr. Wilson’s laboratory helped identify a defect in the innate immune system of the lung which contributes to the chronic airway respiratory infections characteristic of this disease. Molecules are present in the airway surface fluid which contribute to host defense; these have been characterized as a prelude to evaluating how they are deranged in CF. Therapeutic interventions primarily emphasize the use of somatic gene transfer to correct inherited defects. A number of studies utilize vectors based on DNA viruses such as recombinant adenovirus and adeno-associated virus (AAV). Dr. Wilson's group has discovered a new family of AAVs in human and nonhuman primates and shown they undergo substantial recombination in vivo. They appear to be excellent gene transfer vectors. More recently, Dr. Wilson’s group has exploited the biology of the lentiviral vector to achieve stable and long-term gene transfer in non-dividing cells.
Dr. Wilson's studies of immune responses to gene transfer vectors suggested the use of these constructs in eliciting immune responses in the setting of vaccines. The basic concept is to utilize a recombinant adenovirus to activate T and B cell responses to gene products derived from other human pathogens thereby providing protective immunity to these pathogens. The focus of this work is the development of vaccines against biologic weapons and emerging infections such as Ebola virus and SARS coronavirus. Dr. Wilson's group is directly involved in the study of these pathogens in specialized containment facilities at Penn and collaborating institutions.
Rotation Projects
1. Structural biology of AAV capsids
2. Engineering of AAV capsids to improve vector performance
3. Biology of AAV immunology in mice and monkeys
4. Application of AAV vectors for treatment of animals models of human genetic diseases
5. Biology of persistence of endogenous adenoviruses in nonhuman primates.
Lab personnel:
Christie Bell, Graduate Student
Susan Faust, Ph.D., Postdoctoral Researcher
Jenny Greig, Ph.D., Postdoctoral Researcher
Brittney Gurda, Ph.D., Postdoctoral Researcher
Sadik Kassim, Ph.D., Postdoctoral Researcher
Suri Somanathan, Ph.D., Postdoctoral Researcher
Lili Wang, Ph.D., Research Assistant Professor
Thomas Wang, Ph.D., Senior Research Investigator
Ru Xiao, Ph.D., Postdoctoral Researcher
Peter Bell, Ph.D., Director - Cell Morphology
Roberto Calcedo, Ph.D., Manager - Immunology Core
Julie Johnston, Ph.D., Director - Vector Core
Maria Limberis, Ph.D., Research Assistant Professor - Animal Models
Selected Publications
Brantly, M. L., Chulay, J. D., Wang, L., Mueller, C., Humphries, M., Spencer, L. T., Rouhani, F., Conlon, T. J., Calcedo, R., Betts, M. R., Spencer, C., Byrne, B. J., Wilson, J. M., Flotte, T. R.: Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci U S A 2009.
Limberis, M. P., Bell, C. L., Wilson, J. M.: Identification of the murine firefly luciferase-specific CD8 T-cell epitopes. Gene Ther 16(3): 441-7, 2009.
Limberis, M. P., Bell, C. L., Heath, J., Wilson, J. M.: Activation of Transgene-specific T Cells Following Lentivirus-mediated Gene Delivery to Mouse Lung. Mol Ther 2009.
Gao, G., Wang, Q., Calcedo, R., Mays, L., Bell, P., Wang, L., Vandenberghe, L. H., Grant, R., Sanmiguel, J., Furth, E. E., Wilson, J. M.: Adeno-Associated Virus-Mediated Gene Transfer to Nonhuman Primate Liver Can Elicit Destructive Transgene-Specific T Cell Responses. Hum Gene Ther 2009.
Flotte, T. R., Fischer, A. C., Goetzmann, J., Mueller, C., Cebotaru, L., Yan, Z., Wang, L., Wilson, J. M., Guggino, W. B., Engelhardt, J. F.: Dual Reporter Comparative Indexing of rAAV Pseudotyped Vectors in Chimpanzee Airway. Mol Ther 2009.
Fein, D. E., Limberis, M. P., Maloney, S. F., Heath, J. M., Wilson, J. M., Diamond, S. L.: Cationic Lipid Formulations Alter the In Vivo Tropism of AAV2/9 Vector in Lung. Mol Ther 2009.
Calcedo, R., Vandenberghe, L. H., Roy, S., Somanathan, S., Wang, L., Wilson, J. M.: Host immune responses to chronic adenovirus infections in human and nonhuman primates. J Virol 83(6): 2623-31, 2009.
Calcedo, R., Vandenberghe, L. H., Gao, G., Lin, J., Wilson, J. M.: Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis 199(3): 381-90, 2009.
Breous, E., Somanathan, S., Wilson, J. M.: Identification of the immunodominant cytotoxic T-cell epitope of human alpha-1 antitrypsin. Gene Ther 16(11): 1380-2, 2009.
Breous, E., Somanathan, S., Vandenberghe, L. H., Wilson, J. M.: Hepatic regulatory T cells and Kupffer cells are crucial mediators of systemic T cell tolerance to antigens targeting murine liver. Hepatology 50(2): 612-21, 2009.
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Last updated: 01/24/2013
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