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James M. Wilson, MD, PhD Researcher

Rose H. Weiss Orphan Disease Center Director's Professor Professor of Pediatrics

Dr. Wilson is employed by Penn Medicine.

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Memberships

Advisory Committee for the Career Awards in the Biomedical Sciences Program, Burroughs Welcome Fund, National Albion College, National American Association for the Advancement of Science, International American Association for the Study of Liver Diseases, International American Federation for Clinical Research, International American Society for Clinical Investigation, International American Society for Microbiology, International American Society of Gene Therapy, National American Society of Gene Therapy, National Association for Patient-Oriented Research, National Board of Advisors, The Stop ALD Foundation, National Executive Committee, Combined Degree Physician Scholar Program, University of Pennsylvania, National External Advisory Committee, Therapeutics Development Centers Program, Cystic Fibrosis Foundation, National External Scientific Advisory Committee, Pittsburgh Human Gene Therapy Center, National Federation of American Societies for Experimental Biology, National Gene Therapy Task Force, Muscular Dystrophy Association, International John Morgan Society, National Molecular Medicine Society, International NIDDK Medical Student Research Training Program University of Pennsylvania, Advisory Committee, National Regenerative Medicine Society, International Scientific Task Force, Juvenile Diabetes Research Foundation, International

Hospital Affiliation

Dr. Wilson is employed by Penn Medicine.

Research

Description of Research Expertise:

Research Interests
Dr. Wilson’s laboratory focuses on the development of gene transfer vectors and their application in the treatment of a variety of acquired and inherited diseases. He has recently isolated new families of simian-based adenoviruses and adeno-associated viruses. Characterization of these new isolates has yielded important insights into basic virology. More importantly, recombinant versions of these viruses have shown to be useful as improved gene transfer vehicles to a variety of targets. These studies have included gene transfer to lung for the treatment of CF and to liver for the treatment of inherited dyslipidemias. Another major effort is the development of genetic vaccines against a number of biologic weapons and emerging infections such as Ebola virus and the SARS coronavirus.

Key words: adenovirus, adeno-associated virus (AAV), gene therapy, gene transfer, lentivirus.

Description of Research
Dr. Wilson is interested in the study of inherited diseases and the development of effective therapies. One theme is the evaluation of cell biology relevant to organs affected in inherited diseases such as the lung in cystic fibrosis, the muscle in inherited muscular dystrophies and the liver in inborne errors of metabolism. Dr. Wilson’s group uses animal models to evaluate the regenerative capacity of these organs as well as the existence of stem cells. In characterizing cystic fibrosis, Dr. Wilson’s laboratory helped identify a defect in the innate immune system of the lung which contributes to the chronic airway respiratory infections characteristic of this disease. Molecules are present in the airway surface fluid which contribute to host defense; these have been characterized as a prelude to evaluating how they are deranged in CF. Therapeutic interventions primarily emphasize the use of somatic gene transfer to correct inherited defects. A number of studies utilize vectors based on DNA viruses such as recombinant adenovirus and adeno-associated virus (AAV). Dr. Wilson's group has discovered a new family of AAVs in human and nonhuman primates and shown they undergo substantial recombination in vivo. They appear to be excellent gene transfer vectors. More recently, Dr. Wilson’s group has exploited the biology of the lentiviral vector to achieve stable and long-term gene transfer in non-dividing cells.

Dr. Wilson's studies of immune responses to gene transfer vectors suggested the use of these constructs in eliciting immune responses in the setting of vaccines. The basic concept is to utilize a recombinant adenovirus to activate T and B cell responses to gene products derived from other human pathogens thereby providing protective immunity to these pathogens. The focus of this work is the development of vaccines against biologic weapons and emerging infections such as Ebola virus and SARS coronavirus. Dr. Wilson's group is directly involved in the study of these pathogens in specialized containment facilities at Penn and collaborating institutions.

Rotation Projects
1. Structural biology of AAV capsids
2. Engineering of AAV capsids to improve vector performance
3. Biology of AAV immunology in mice and monkeys
4. Application of AAV vectors for treatment of animals models of human genetic diseases
5. Biology of persistence of endogenous adenoviruses in nonhuman primates.


Lab personnel:
Peter Bell, PhD - Director, Histology Core
Roberto Calcedo, PhD - Director, Immunology Core
Shu Jen Chen, PhD - Associate Director, Vector Core, Quality Control
Tami Goode, DVM, DACLAM - Director, Animal Models Core
Jenny Greig, PhD - Senior Research Investigator
Julie Johnston, PhD - Executive Director, Vector Operations
Maria Limberis, PhD - Research Associate Professor
Martin Lock, PhD - Director, Vector Process Development
Arbans Sandhu, PhD - Associate Director, Vector Core, Production
Suri Somanathan, PhD - Senior Research Investigator
Anna Tretiakova, PhD - Senior Director, Antibody Therapeutics
Lili Wang, PhD - Research Associate Professor
Qiang (Thomas) Wang, PhD - Senior Research Investigator

Scott Ashley - PhD candidate
April Giles - PhD candidate
Christian Hinderer, PhD - MD candidate
Kalyani Nambiar - PhD candidate
William Rothwell - PhD candidate

Open postdoctoral positions: http://www.med.upenn.edu/postdoc/positions.shtml

Selected Publications:

Tenney R, Bell C, Wilson JM: AAV8 capsid variable regions at the two-fold symmetry axis contribute to high liver transduction by mediating nuclear entry and capsid uncoating Virology 454-455 : 227-236,2014.

Mays LE, Wang L, Lin J, Bell P, Crawford A, Wherry EJ, Wilson JM: AAV8 induces tolerance in murine muscle as a result of poor APC transduction, T cell exhaustion and minimal MHCI upregulation on target cells Mol Ther 22 (1): 28-41,2014.

Huang J, Li X, Coelho-dos-Reis JGA, Wilson JM, Tsuji M: An AAV Vector-Mediated Gene Delivery Approach Facilitates Reconstitution of Functional Human CD8+ T Cells in Mice PLoS ONE 9 (2): 2014.

Mueller C, Chulay JD, Trapnell BC, Humphries M, Carey B, Sandhaus RA, McElvaney NG, Messina L, Tang Q, Rouhani FN, Campbell-Thompson M, Dongtao Fu A, Yachnis A, Knop DR, Ye G, Brantly M, Calcedo R, Somanathan S, Richman LP, Vonderheide RH, Hulme MA, Brusko TM, Wilson JM and Flotte TR: Human Treg responses allow sustained recombinant adeno-associated virus–mediated transgene expression J Clin Invest 123 (12): 5310-5318,2013.

Lock M, Alvira MR, Chen SJ, Wilson JM.: Absolute Determination of Single-Stranded and Self-Complementary AAV Vector Genome Titers by Droplet Digital PCR Hum Gene Ther Methods : 2013.

Chen SJ, Sanmiguel J, Lock M, McMenamin D, Draper C, Limberis MP, Kassim SH, Somanathan S, Bell P, Johnston JC, Rader DJ, and Wilson JM: Bio-distribution of AAV8 vectors expressing human LDL receptor in a mouse model of homozygous familial hypercholesterolemia Hum Gene Ther Clin Dev 24 (4): 154-160,2013.

Faust SM, Bell P, Zhu Y, Sanmiguel J and Wilson JM: The Role of Apoptosis in Immune Hyporesponsiveness Following AAV8 Liver Gene Transfer Molecular Therapy : 2013.

Calcedo R, Griesenbach U, Dorgan DJ, Soussi S, Boyd AC, Davies JC, Higgins TE, Hyde SC, Gill DR, Innes JA, Porteous DJ, Alton EW, Wilson JM, Limberis MP: Self-Reactive CFTR T Cells in Humans: Implications for Gene Therapy Hum Gene Ther Clin Dev 24 (3): 108-15,2013.

Mays LE, Wang L, Tenney R, Bell P, Nam HJ, Lin J, Gurda B, Van Vliet K, Mikals K, Agbandje-McKenna M, Wilson JM: Mapping the structural determinants responsible for enhanced T cell activation to the immunogenic adeno-associated virus capsid from isolate rhesus J Virol 87 (17): 9473-85,2013.

Zhong L, Li S, Li M, Xie J, Zhang Y, Lee B, Batshaw ML, Wilson JM, Gao G: Vector sequences are not detected in tumor tissue from research subjects with ornithine transcarbamylase deficiency who previously received adenovirus gene transfer Hum Gene Ther 24 (9): 814-9,2013.

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Academic Contact Info

125 S. 31st Street,
Suite 2000 TRL

Philadelphia, PA 19104-3403
Phone: (215) 573-9020