Center for Orphan Disease Research and Therapy
James M. Wilson, M.D., Ph.D
Director, Gene Therapy Program
Professor, Department of Pathology & Laboratory Medicine, Division of Transfusion Medicine
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.
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.