New Bolton Center Kennett Square, PA
Emergencies & Appointments:
Ryan Hospital Philadelphia, PA

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

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

Professor of Pathology, 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 and stem cell engraftment 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.

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.

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.

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.

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.

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.

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 a-synuclein oligomers. Nature Neurosci. 20: 1560-1568, 2017.

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.

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.

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.

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.

A.B. (Philosophy) Ripon College, 1969

post-bacc (general sciences) Harvard Univ, 1975

post-bac (general sciences) Univ Penn, 1977

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

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

Schools of Medicine and Veterinary Medicine, University of Pennsylvania (1978 to 1984)
NIH Veterinary Medical Scientist Training Program

Sloan-Kettering Institure for Cancer Research, Memorial Sloan-Kettering Cancer Center (1985 to 1987)
Exxon Fellow, Molecular Biology Program