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John H. Wolfe VMD, PhD
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Professor of Pathobiology in Pediatrics (Neurology)
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Department: Pediatrics
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Graduate Group Affiliations
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Contact information
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Children's Hospital of Philadelphia
26 502-G Abramson Research Center
43 3615 Civic Center Boulevard
Philadelphia, PA 19104-4399
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26 502-G Abramson Research Center
43 3615 Civic Center Boulevard
Philadelphia, PA 19104-4399
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Office: (215) 590-7028
34 Fax: (215) 590-3779
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34 Fax: (215) 590-3779
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Email:
jhwolfe@vet.upenn.edu
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jhwolfe@vet.upenn.edu
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Education:
21 9 A.B. 17 (Philosophy) c
26 Ripon College, 1969.
21 e post-bacc 1d (general sciences) c
25 Harvard Univ, 1975.
21 d post-bac 1d (general sciences) c
22 Univ Penn, 1977.
21 b V.M.D. 20 (Veterinary Medicine) c
3e University of Pennsylvania, cum laude, 1982.
21 a Ph.D. 2e (Immunology: retroviruses/genetics) c
33 University of Pennsylvania, 1986.
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21 9 A.B. 17 (Philosophy) c
26 Ripon College, 1969.
21 e post-bacc 1d (general sciences) c
25 Harvard Univ, 1975.
21 d post-bac 1d (general sciences) c
22 Univ Penn, 1977.
21 b V.M.D. 20 (Veterinary Medicine) c
3e University of Pennsylvania, cum laude, 1982.
21 a Ph.D. 2e (Immunology: retroviruses/genetics) c
33 University of Pennsylvania, 1986.
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Links
87 Neuroscience Graduate Group
43 Cell and Molecular Biology graduate group faculty webpage.
84 Wolfe Lab
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Permanent link87 Neuroscience Graduate Group
43 Cell and Molecular Biology graduate group faculty webpage.
84 Wolfe Lab
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89 gene transfer and stem cell engraftment in the central nervous system, genetic diseases, animal models, mechanisms of pathology.
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a7 Key words: gene therapy, viral vectors, brain, pathogenesis, lysosomal enzymes, neural stem cells, MRI and PET imaging, animal models, genetic diseases.
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26 Description of Research
2ee 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.
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20 Rotation Projects
1ac 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.
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Description of Research Expertise
2a Research Interests89 gene transfer and stem cell engraftment in the central nervous system, genetic diseases, animal models, mechanisms of pathology.
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a7 Key words: gene therapy, viral vectors, brain, pathogenesis, lysosomal enzymes, neural stem cells, MRI and PET imaging, animal models, genetic diseases.
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26 Description of Research
2ee 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.
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20 Rotation Projects
1ac 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.
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139 Hunter JE, Molony CM, Bagel JH, O’Donnell PA, Kaler SG, Wolfe JH: Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery. Mol. Ther. Meth. & Clin. Devel. 26: 384-393, 2022.
111 Siddiqi, F., Trakimas, A.L., Joseph, D.J., Lippincott, M.L., Marsh, E.D., Wolfe, J.H.: Islet1 precursors contribute to mature interneuron subtypes in mouse neocortex. Cereb Cortex 31: 5206-5224, 2021.
16f Yoon, S.Y., Hunter, J.E., Chawla, S., Clarke, D.L., Molony, C., O'Donnell, P., Bagel, J.H., Kumar, M., Poptani, H., Vite, C.H. and Wolfe, J.H.: Global central nervous system correction in large brain model of human alpha-mannosidosis by intravascular gene therapy. Brain 143: 2058-2072 2020.
190 Cuoco JA, Esposito AW, Moriarty S, Tang Y, Seth S, Toia AR, Kampton EB, Mayr Y, Khan M, Mullen BR, Ackman JB, Siddiqi F, Wolfe JH, Savinova O, Ramos RL.: Malformation of the posterior cerebellar vermis is a common neuroanatomical phenotype of genetically-engineered mice on the C57BL/6 background. Cerebellum 17: 173-190, 2018.
196 Mor, D.E., Tsika, E., Mazzulli, J.R., Gould, N.S., Kim, H., Daniels, M.J., Doshi, S., Gupta, P., Grossman, J.L., Tan, V.X., Kalb, R.G., Caldwell, K.A., Caldwell, G.A., Wolfe, J.H. and Ischiropoulos, H. : Dopamine-induced nigrostriatal degeneration is mediated by soluble α-synuclein oligomers. Nature Neurosci. 20: 1560-1568, 2017.
11b Parente, M.K., Rozen, R., Seeholzer, S.H. and Wolfe, J.H. : Integrated analysis of proteome and transcriptome changes in the mucopolysaccharidosis type VII mouse hippocampus. Mol Genet Metab 118: 41-54, 2016.
10d Yoon, S.Y., Bagel, J.H., O'Donnell, P.A., Vite, C.H. and Wolfe, J.H.: Clinical improvement of alpha-mannosidosis cat following a single cisterna magna infusion of AAV1. Mol. Ther. 24: 26-33, 2016.
163 Kumar, M., Duda, J.T., Yoon, S.Y., Bagel, J., O'Donnell, P., Vite, C., Pickup, S., Gee, J., Wolfe, J.H. and Poptani, H. : Diffusion tensor imaging for assessing gray and white matter abnormalities in a feline model of alpha-mannosidosis. J. Neuropath. Exp. Neurol. 75: 35-43, 2016.
172 Hjelm, B.E., Grunseich, C., Gowing, G., Avalos, P., Tian, J., Shelley, B.C., Mooney, M., Narwani, K., Shi, Y., Svendsen, C.N., Wolfe, J.H., Fischbeck, K.H. and Pierson, T.M.: Mifepristone-inducible transgene expression in neural progenitor cells in vitro and in vivo. Gene Ther. 23: 424-37, 2016.
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Selected Publications
1a9 Ripolles-Garcia, A., Dolgova, N., Phillips, M.J., Savina, S., Ludwig, A.L., Stuedemann, S.A., Nlebedum, U., Wolfe, J.H., Garden, O., Gamm, D.M., Aguirre, G.D., Beltran, W.A.: Systemic immunosuppression promotes survival and integration of subretinally-implanted human ESC-derived photoreceptor precursors in dogs. Stem Cell Reports 17: 1824-1841, 2022.139 Hunter JE, Molony CM, Bagel JH, O’Donnell PA, Kaler SG, Wolfe JH: Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery. Mol. Ther. Meth. & Clin. Devel. 26: 384-393, 2022.
111 Siddiqi, F., Trakimas, A.L., Joseph, D.J., Lippincott, M.L., Marsh, E.D., Wolfe, J.H.: Islet1 precursors contribute to mature interneuron subtypes in mouse neocortex. Cereb Cortex 31: 5206-5224, 2021.
16f Yoon, S.Y., Hunter, J.E., Chawla, S., Clarke, D.L., Molony, C., O'Donnell, P., Bagel, J.H., Kumar, M., Poptani, H., Vite, C.H. and Wolfe, J.H.: Global central nervous system correction in large brain model of human alpha-mannosidosis by intravascular gene therapy. Brain 143: 2058-2072 2020.
190 Cuoco JA, Esposito AW, Moriarty S, Tang Y, Seth S, Toia AR, Kampton EB, Mayr Y, Khan M, Mullen BR, Ackman JB, Siddiqi F, Wolfe JH, Savinova O, Ramos RL.: Malformation of the posterior cerebellar vermis is a common neuroanatomical phenotype of genetically-engineered mice on the C57BL/6 background. Cerebellum 17: 173-190, 2018.
196 Mor, D.E., Tsika, E., Mazzulli, J.R., Gould, N.S., Kim, H., Daniels, M.J., Doshi, S., Gupta, P., Grossman, J.L., Tan, V.X., Kalb, R.G., Caldwell, K.A., Caldwell, G.A., Wolfe, J.H. and Ischiropoulos, H. : Dopamine-induced nigrostriatal degeneration is mediated by soluble α-synuclein oligomers. Nature Neurosci. 20: 1560-1568, 2017.
11b Parente, M.K., Rozen, R., Seeholzer, S.H. and Wolfe, J.H. : Integrated analysis of proteome and transcriptome changes in the mucopolysaccharidosis type VII mouse hippocampus. Mol Genet Metab 118: 41-54, 2016.
10d Yoon, S.Y., Bagel, J.H., O'Donnell, P.A., Vite, C.H. and Wolfe, J.H.: Clinical improvement of alpha-mannosidosis cat following a single cisterna magna infusion of AAV1. Mol. Ther. 24: 26-33, 2016.
163 Kumar, M., Duda, J.T., Yoon, S.Y., Bagel, J., O'Donnell, P., Vite, C., Pickup, S., Gee, J., Wolfe, J.H. and Poptani, H. : Diffusion tensor imaging for assessing gray and white matter abnormalities in a feline model of alpha-mannosidosis. J. Neuropath. Exp. Neurol. 75: 35-43, 2016.
172 Hjelm, B.E., Grunseich, C., Gowing, G., Avalos, P., Tian, J., Shelley, B.C., Mooney, M., Narwani, K., Shi, Y., Svendsen, C.N., Wolfe, J.H., Fischbeck, K.H. and Pierson, T.M.: Mifepristone-inducible transgene expression in neural progenitor cells in vitro and in vivo. Gene Ther. 23: 424-37, 2016.
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5b © The Trustees of the University of Pennsylvania | Site best viewed a in a supported browser. | Site Design: 57 PMACS Web Team. 3 22
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