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USC - University of Southern California Cardiothoracic Surgery at University of Southern California Keck School of Medicine
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Mary Kearns-Jonker, Ph.D.

Mary Kearns-Jonker, Ph.D.
Assistant Professor of Research




Contact

Phone: (323) 361-8319
Fax: (323) 662-1709
Email: mkearns@chla.usc.edu

Research Interest

  • Characterization of the Xenoantibody Response to Porcine Xenoantigens in Humans and Primates
  • Gene Therapy Approach to Preventing Xenograft Rejection

Antibody responses present a major immunological barrier to the use of pig organs for transplantation in humans. We have recently identified the immunoglobulin VH genes encoding xenoantibodies in humans. Single chain antibodies encoded by these genes react with the alpha-gal carbohydrate and block up to 80% of human natural antibody binding to pig cells. We are using site-directed mutagenesis and chain shuffling to study the role of xenoantibody structure in binding specificity for the alpha-gal epitope. The manipulation of the xenoantibody response by the application of gene therapy has been tested in vitro and will be studied in animal models applicable to pig-to-human xenotransplantation.

Recent Publications

  1. Kearns-Jonker M, Fischer-Lougheed J, Shulkin I, Kleihauer A, Mitsuhashi N, Kohn DB, Weinberg K, d’Starnes V, and D.V.Cramer The use of lentiviral vectors to induce long-term tolerance to gal+ heart grafts, Transplantation, in press, 2004.
  2. Cramer DV, Wu GD, and Kearns-Jonker M. Synthesis of xenoantibodies at the gene and molecular level. Current Opinion in Organ Transplantation 6:42-46, 2002.
  3. Kearns-Jonker, M., Swensson, J., Ghiuzeli, C., Chu, W., Osame, Y., Starnes, V., and Cramer, D.V. The human xenoantibody response to porcine xenoantigens is encoded by IGHV3-11 and IGHV3-74 immunoglobulin IgVH germline progenitors. J. Immunology 163:8 4399-4412, 1999.
  4. Kearns-Jonker, M., Fraiman, M., Chu, W., Gochi, E., Michel, J., Wu, G.D., and Cramer, D.V.C. Xenoantibodies to pig endothelium are expressed in germline configuration and share a conserved immunoglobulin VH gene structure with antibodies to common infectious agents. Transplantation 65:1515-1519,1998.
  5. Kearns-Jonker, M.K., Cramer, D.V., Dane, L.A., Swensson, J.M., and Makowka, L. Human serum reactivity to porcine endothelial cells following antisense-mediated downregulation of GpIIIa expression. Transplantation 63:588-593,1997.

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