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Education:
BSc 1979 Microbiology & Immunology - McGill University, Montreal, Canada
MSc 1981 Anatomy - McGill University, Montreal, Canada
PhD 1985 Anatomy - McGill University, Montreal, Canada
Postdoctoral Research Fellowship:
1985 - 1992 National Institutes of Health, Bethesda, Maryland
Started at USC: 1998 Research Topics: Immunology, Cardiovascular & Skeletal Muscle Diseases, Gene Therapy, Human/Mammalian Genetics
Research Description
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.
10 Selected Publications:
Click here to view all the publications for this faculty
Kiernan K,Harnden I,Gunthart M,Gregory C,Meisner J,Kearns-Jonker M - The anti-non-gal xenoantibody response to xenoantigens on gal knockout pig cells is encoded by a restricted number of germline progenitors. - Am J Transplant [2008] Sep;8(9):1829-39 PubMed
Doki T,Mello M,Mock D,Evans JM,Kearns-Jonker M - Intragraft gene expression profile associated with the induction of tolerance. - BMC Immunol [2008] Feb 11;9():5 PubMed
Gunthart M,Kearns-Jonker M - Gene therapy for the induction of chimerism and transplant tolerance. - Curr Gene Ther [2007] Dec;7(6):411-20 PubMed
Fischer-Lougheed J,Gregory C,White Z,Shulkin I,Gunthart M,Kearns-Jonker M - Identification of an anti-idiotypic antibody that defines a B-cell subset(s) producing xenoantibodies in primates. - Immunology [2008] Mar;123(3):390-7 PubMed
Zahorsky-Reeves JL,Kearns-Jonker MK,Lam TT,Jackson JR,Morris RE,Starnes VA,Cramer DV - The xenoantibody response and immunoglobulin gene expression profile of cynomolgus monkeys transplanted with hDAF-transgenic porcine hearts. - Xenotransplantation [2007] Mar;14(2):135-44 PubMed
Kearns-Jonker M,Barteneva N,Mencel R,Hussain N,Shulkin I,Xu A,Yew M,Cramer DV - Use of molecular modeling and site-directed mutagenesis to define the structural basis for the immune response to carbohydrate xenoantigens. - BMC Immunol [2007] Mar 12;8():3 PubMed
Mitsuhashi N,Wu GD,Zhu H,Kearns-Jonker M,Cramer DV,Starnes VA,Barr ML - Rat chemokine CXCL11: structure, tissue distribution, function and expression in cardiac transplantation models. - Mol Cell Biochem [2007] Feb;296(1-2):1-9 PubMed
Evans JM,Doki T,Fischer-Lougheed J,Davicioni E,Kearns-Jonker M - Expression changes in tolerant murine cardiac allografts after gene therapy with a lentiviral vector expressing alpha1,3 galactosyltransferase. - Transplant Proc [2006] Dec;38(10):3172-80 PubMed
Fischer-Lougheed JY,Tarantal AF,Shulkin I,Mitsuhashi N,Kohn DB,Lee CC,Kearns-Jonker M - Gene therapy to inhibit xenoantibody production using lentiviral vectors in non-human primates. - Gene Ther [2007] Jan;14(1):49-57 PubMed
Zahorsky-Reeves JL,Gregory CR,Cramer DV,Patanwala IY,Kyles AE,Borie DC,Kearns-Jonker MK - Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes. - BMC Immunol [2006] Mar 20;7():3 PubMed
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