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James
M. Wilson, M.D., Ph.D.
John
Herr Musser Professor of Research Medicine
Professor, Department of Pathology and Laboratory Medicine
Gene
Therapy and Vaccines Program
Address
Gene
Therapy Program
Translational Research Laboratory
125 South 31st Street, Suite 2000
Philadelphia PA 19104-3403
Office tel.: 215 898-0226
Fax: 215 898-6588
E-mail: wilsonjm@mail.med.upenn.edu
Link(s)
Dept of Path and
Lab Medicine
Dept
of Med, Div of Med Genetics
Education
Albion College, Albion, Michigan: BA (Chemistry), 1973-1977.
University of Michigan Medical School, Ann Arbor, Michigan:
PhD (Biological Chemistry), 1977-1984.
University of Michigan Medical School, Ann Arbor, Michigan:
MD, 1977-1984.
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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.
Selected
Publications
Vandenberghe LH, Wang L, Somanathan S, Zhi Y, Figueredo J, Calcedo R, Sanmiguel J, Desai RA, Chen CS, Johnston J, Grant RL, Gao G, Wilson JM. Heparin binding directs activation of T cells against adeno-associated virus serotype 2 capsid. Nat Med, 12:967-971, 2006.
Wang L, Figueredo J, Calcedo R, Lin J, Wilson JM. Cross presentation of AAV2 capsids activates cytotoxic T cells but does not render hepatocytes effective cytolytic targets. Human Gene Therapy, 18:185-189, 2007.
Roy S, Clawson DS, Lavrukhin O, Sandhu A, Miller J, Wilson JM. Rescue of chimeric adenoviral vectors to expand the serotype repertoire. J Virol Methods, 141: 14-21, 2007.
Kobinger GP, Figueredo JM, Rowe T, Zhi Y, Gao G, Sanmiguel JC, Bell P, Wivel NA, Zitzow LA, Flieder DB, Hogan RJ, Wilson JMW. Adenovirus-Based Vaccine Prevents Pneumonia in Ferrets Challenged with the SARS coronavirus and Stimulates Robust Immune Responses in Macaques. Vaccine ,25:5220-5231, 2007
Limberis M, Figueredo J, Calcedo, R, Wilson JM. Identification of murine CFTR protein-specific CD8 T Cell epitopes. Mol Ther,36:529-533, 2007.
Search PubMed for more articles
Lab
Rotation
Projects
- Identification of new primate adenoviruses
- Applications of DNA viruses as vaccines for infectious diseases
- Engineering the AAV capsid for use as a gene therapy vector
- Lab
personnel
Christie Bell, Graduate Student
Katya Breous, Ph.D., Postdoctoral Researcher
Sadik Kassim, Ph.D., Postdoctoral Researcher
Marty Keough, Ph.D., Postdoctoral Researcher
Maria Limberis, Ph.D., Senior Research Investigator
Jianping Lin, Ph.D., Postdoctoral Researcher
Lauren Mays, Graduate Student
Soumitra Roy, M.D., Senior Research Investigator
Suri Somanathan, Ph.D., Postdoctoral Researcher
Luk Vandenberghe, Ph.D., Senior Research Investigator
Lili Wang, Ph.D., Senior Research Investigator
last updated 7/2008
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