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Member Information
Paula Henthorn, PhD
Associate Professor, Department of Medical Genetics
School of Veterinary Medicine
Office Phone: 215-898-9601
Office Fax: 215-573-2162
Email: henthorn@vet.upenn.edu
Website(s):
Education: PhD 1984, University of Wisconsin - Genetics
Keywords: comparative genetics, gene transfer
Research and/or Clinical Interests:
Molecular basis of human and animal genetic diseases, comparative genetics, gene transfer for the treatment of genetic diseases.
Summary:
Our research program centers on the molecular basis of genetic disease in humans and in domestic animals with genetic diseases homologous to those found in humans. Current major focus in on human hypophosphatasia and canine Xlinked severe combined immunodeficiency (XSCID). X-linked severe combined immunodeficiency (XSCID) in humans and dogs is characterized by profound defects in both cellular and humoral immunity and is caused by mutations in the gene encoding the gamma chain of the interleukin-2 receptor, a component of multiple cytokine receptors. We are using the XSCID dog model to develop approaches to somatic cell gene transfer as a treatment for immunodeficiencies. Hypophosphatasia is characterized by defective bone formation and deficient tissue-nonspecific alkaline phosphatase (TNSALP) enzyme activity. Although the presence of TNSALP on the cell membrane of osteoblasts appears to be necessary for bone mineralization, the molecular pathogenesis of hypophosphatasia is not understood. Our goals are to identify the spectrum of hypophosphatasia TNSALP mutations, to correlate abnormal TNSALP gene structure or expression with defective bone mineralization, and to investigate the regulation of TNSALP gene expression. Other diseases under study include mucopolysaccharidosis VII, conotruncal defects, glycogen storage diseases type IV, and cystinuria.
Representative Publications:
Felsburg PJ, Somberg RL, Hartnett BJ, Suter SF, Henthorn PS, Moore PF, Weinberg KI, and Ocha H. (1997) Full immunological reconstitution following non-conditioned bone marrow transplantation for canine X-linked severe combined immunodeficiency. Blood 90:3214-3221.
Ray J, Bouvet A, DeSanto C, Fyfe JC, Xu D, Wolfe JH, Aguirre GD, Patterson DF, Haskins ME, and Henthorn PS. (1998) Cloning of the canine beta-glucuronidase cDNA, mutation identification in canine MPS VII, and retroviral vector-mediated correction of MPS VII cells. Genomics 48:248-253.
