The Wolfe laboratory investigates direct gene transfer and neural stem cell engraftment in the central nervous system with a focus on the lysosomal storage diseases that, like most inherited metabolic disorders in the CNS, have global lesions.
Neural stem cells,
Animal models of human diseases,
gene transfer in the central nervous system, genetic diseases, animal models, mechanisms of pathology.
Key words: gene therapy, viral vectors, brain, pathogenesis, lysosomal enzymes, neural stem cells, MRI and PET imaging, animal models, genetic diseases.
Description of Research
Animal homologs of human genetic diseases are used as test systems for gene transfer by viral vectors. The approaches for transferring genes to the brain currently being investigated are ex vivo gene transfer using retrovirus and lentivius vector-modified neural stem cells transplanted to the brain and direct injection of herpesvirus, adeno-associated virus, and lentivirus vectors. The studies involve comparisons of promoters, properties of transduction for different cell types and various subregions of the brain. New methods to follow cell fate and gene expression in the live animal are being explored using MRI and PET techniques. Studies are also being directed towards better understanding of the mechanism of disease in the brain.
Rotation Projects for 2009-2010
Rotation projects are related to the molecular design and engineering of vectors, understanding the fate of vector-transferred genes in the brain, the regulation of foreign gene expression from vectors, neural stem cell biology,induced pluripotent stem cells (iPS), imaging studies, and proteomics and genomics analysis of neurodegenerative lesions. Projects can be tailored to the interest and experience of the student.
- Professor of Pathology and Medical Genetics in Pediatrics at University of Pennsylvania School of Medicine (2005– present)
- Ph.D., Immunology: retroviruses/genetics, University of Pennsylvania (1986)
- V.M.D., veterinary medicine, University of Pennsylvania, cum laude (1982)
- post-bac, general sciences, Univ Penn (1977)
- post-bacc, general sciences, Harvard Univ (1975)
- A.B., Philosophy, Ripon College (1969)
- Magnitsky, S., Vite, C.H., Delikatny, E.J., Pickup, S., Wehrli, S., Wolfe, J.H. and Poptani, P.. Magnetic resonance spectroscopy of the cerebral cortex and cerebellum distinguishes individual cats affected with alpha-mannosidosis from normal cats.. NMR Biomed.. Vol in press. 2009.
- Husain, T., Passini, M.A., Parente, M.K., Fraser, N.W. and Wolfe, J.H. (2009). Long-term AAV vector gene and protein expression in mouse brain from a small pan-cellular promoter is similar to neural cell promoters.. Gene Ther.. Vol 16. 2009:927-932.
- Walton R.M., Magnitsky, S.G., Seiler, G.S., Poptani H., and Wolfe J.H.. Transplantation and magnetic resonance imaging of canine neural progenitor cell grafts in the postnatal dog brain.. J. Neuropath. Exp. Neurol.. (67) . 2008:954-962.
- Cearley, C.N., Vandenberghe, L.H., Carnish, E.R., Parente, M.K., Wilson, J.M. and Wolfe, J.H.. Expanded repertoire of AAV vector serotypes mediate unique patterns of transduction in mouse brain.. Mol. Ther.. Vol 16. 2008:1710-1718.
- Vite, C.H., Magnitsky, S., Aleman, D., O?Donnell, P., Cullen, K., Ding, W., Pickup, S., Wolfe, J.H. and Poptani, H.. Apparent diffusion coefficient reveals gray and white matter disease and T2 mapping detects white matter disease in the brain in feline alpha-mannosidosis.. Am. J. Neuroradiol.,. 2007.
- Cearley, C.N. and Wolfe, J.H.. A single injection of an AAV vector into nuclei with divergent connections results in widespread vector distribution and global correction of a neurogenetic disease.. J. Neurosci. 27: 9928-9940. 2007.
- Magnitsky, S., Walton, R. M. , Wolfe, J. H. and Poptani, H.. Magnetic resonance imaging as a tool for monitoring stem cell therapy.. Neurodegen. Dis. 4: 314-321. 2007.
- Magnitsky, S., Walton, R.M., Wolfe, J.H. and Poptani, H.. Labeling neural stem cells with iron oxide particles for in vivo MRI: effects on proliferation and differentiation.. 2007.
- Berges, B.K., Wolfe, J.H. and Fraser, N.W.. Transduction of brain by herpes simplex virus vectors.. Mol. Ther., 15: 20-29. 2007.
- Walton, R.M. and Wolfe, J.H.. Abnormalities in neural progenitor cells in a dog model of lysosomal storage disease.. J. Neuropath. Exp. Neurol. 66: 760-769. 2007.