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JOHN H. WOLFE, V.M.D., Ph.D., A.B., post-bac, post-bacc

Stokes Investigator of the Joseph Stokes, Jr. Research Institute, Children's Hospital of Philadelphia

Professor of Pathology (with tenure), Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania

Director, Walter Flato Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine. , University of Pennsylvania, School of Veterinary Medicine.

Research Areas: Gene therapy, Neural stem cells, iPS cells, Viral vectors, Animal models of human diseases, Neurological disease, Genetics, Molecular neuropathology, Lysosomal enzymes,

Contact Information:
Children's Hospital of Philadelphia
502-G Abramson Research Center
3615 Civic Center Boulevard

Research Interests
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
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.

Castle, M.J., Perlson, E., Hozbauer, E.L.F., and Wolfe, J.H. Long-distance axonal transport of AAV9 is driven by dynein and kinesin-2 and is trafficked in a highly motile Rab7-positive compartment. Mol. Ther. 22: 554-556, 2014.

Kumar, M., Nasrallah, I.M., Kim, S., Ittyerah, R., Pickup, S., Li, J., Parente, M.K., Wolfe, J.H., and Poptani, H. High-resolution magnetic resonance microscopy and diffusion tensor imaging to assess brain structural abnormalities in the murine mucopolysaccharidosis VII model. J. Neuropath. Exp. Neurol. 73: 39-49, 2014.

Castle, M.J., Gershenson, Z.T., Giles, A.R., Holzbauer, E.L.F., and Wolfe, J.H. Adeno-associated virus serotypes 1, 8, and 9 share conserved mechanisms for anterograde and retrograde axonal transport. Hum. Gene. Ther. 25: 705-20, 2014.

Simonato, M., Bennett, J., Boulis, N.M., Castro, Frink, D.J., Gray, S.J., Lowenstein, P.R., Vendenberghe, L.H., Wilson, T.J., Wolfe, J.H., and Glorioso, J.C. Gene therapy for neurological disorders. Are we getting there? Nat. Rev. Neurol. 9: 277-291, 2013.

Weerakkody, T.N., Patel, T.P., Yue, C., Takano, H., Anderson, H.C., Meaney, D.F., Coulter, D.A., and Wolfe, J.H. Engraftment of exogenous undifferentiated neural stem cells disrupts cortical network activity Mol. Ther. 21: 2258-2267, 2013.

Chaubey, S., and Wolfe, J.H. Transplantation of CD15-enriched murine neural stem cells leads to better survival and increased oligodendrocytes differentiation. Stem Cells Transl. Med. 2: 444-454, 2013.

Parente, M.K., Rozen, R., Cearley, C.N., and Wolfe, J.H., Dysregulation of gene expression in a lysosomal storage disease varies between brain regions implicating unexpected mechanisms of neuropathology PLoS One 7: , 2012.

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. 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. 16: 927-932, 2009.

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. : 954-962, 2008.

V.M.D. (Veterinary Medicine) University of Pennsylvania, cum laude, 1982

Ph.D. (Immunology: retroviruses/genetics) University of Pennsylvania, 1986

A.B. (Philosophy) Ripon College, 1969

post-bac (general sciences) Univ Penn, 1977

post-bacc (general sciences) Harvard Univ, 1975