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John H. Wolfe, V.M.D., Ph.D.
Professor, Pathology and Medical Genetics, School of Veterinary Medicine
and Department of Pediatrics, School of Medicine
Director, Walter Flato Goodman Ctr for Comparative Medical Genetics http://www.vet.upenn.edu/research/centers/ccmg/
502G Abramson Research Building
(215) 590-7028 FAX: (215) 590-3779
email: jhwolfe@vet.upenn.edu
Click here for selected publications since Dr. Wolfe's arrival at Penn
RESEARCH INTERESTS
Somatic gene transfer and therapy for the central nervous system RESEARCH TECHNIQUES
Viral and non-viral gene transfer vectors (retro-, adeno-associated, and herpes viruses; liposomes); cell transplantation in the brain, especially neural stem/progenitor cells; enzymology; general molecular biology methods; evaluation of pathologyRESEARCH SUMMARY
My research focuses on somatic cell gene transfer to the brain. Animal homologues of human neurodegenerative genetic diseases are used as test systems for gene transfer by viral and other vectors. The primary model system is mucopolysaccharidosis (MPS) type VII (Sly disease), a lysosomal storage disorder caused by a deficiency of ß-glucuronidase, which blocks the normal cellular breakdown of glycosaminoglycans. MPS VII animal models (mice, dogs, and cats) are excellent experimental systems to study the fate of gene transfer and cell transplantation in the brain because both the transferred ß-glucuronidase enzymatic activity and changes in pathology can be studied. Several approaches are being investigated and compared to develop technologies that can tailored to specific applications. These are expected to be especially useful in genetically manipulating discrete populations of cells within the developed brain. Ex vivo gene transfer is being studied using retrovirus vector-corrected cells which are transplanted directly into the brain to circumvent the blood-brain barrier. Fibroblasts grafts are used to evaluate variations in vector designs for their ability to support sustained expression of the transferred gene. Multipotent neural progenitor cells, which differentiate into mature normal cells appropriate to their location within the brain, are being evaluated for their ability to deliver engineered cells to many regions of the diseased brain. Direct transduction of brain cells is being evaluated with herpesvirus, adeno-associated virus, and lentivirus vectors. The methods are being evaluated in post-natal and fetal animals.KEY WORDS:
lysosomal storage diseases, CNS, gene therapy, viral vectors, neural stem cells
