Lab Phone Number: (909) 558-4800 Ext. 42031
The increasing shortage of donor organs for transplantation has led to consideration of alternative solutions for patients with end-stage organ failure. Stem cell transplantation and xenotransplantation represent two potential solutions to this problem. Our laboratory is interested in developing methods to block the immune response that currently prevents pig organs from being used for transplantation into humans when allografts from human donors are unavailable. Our research is focused on defining the genetic structure of the antibodies that initiate the rejection of these grafts and in developing small molecules to prevent xenoantibody-mediated rejection. In addition, our group studies the application of cardiomyocytes differentiated from human embryonic stem cells and endogenous cardiac stem cells for myocardial repair. We are interested in the immunobiology of differentiated cardiomyocytes from various sources and in understanding the early gene expression changes that impact the survival of these cells after transplantation in vivo.
1. Kearns-Jonker M , Dai W, Gunthart M, Fuentes T, Yeh Hsiao-Yun, Gerczuk P, Pera M, Mummery C, and Kloner RA. Genetically Engineered Mesenchymal Stem Cells Influence Gene Expression in Donor Cardiomyocytes and the Recipient Heart J Stem Cell Res and Therapy, 2012, S1-S8
2. Evans, JM, Navarro S, Doki T, Mitsuhashi N, and Kearns-Jonker M. Gene transfer of hemeoxygenase 1 using adeno-associated virus serotype 6 vector prolongs cardiac allograft survival (submitted).
3. Harnden I, Kiernan K, and Kearns-Jonker M The anti-non-gal xenoantibody response to galactosyltransferase gene knockout (GalTKO) pig xenografts. Current Opinion in Organ Transplantation 15(2):207-11, 2010
4. Kearns-Jonker M, Dai W and Kloner RA. Stem Cells for the Treatment of Heart Failure. Current Opinion in Molecular Therapeutics 12(4):432-441, 2010
5. Fischer-Lougheed J, Gregory C, White Z, Shulkin I, Gunthart M and Kearns-Jonker M,. Identification of an anti-idiotypic antibody that defines B cell subset(s) producing xenoantibodies in primates. Immunology 123(3):390-7, 2008
6. Doki T, Mello M, Mock D, Evans JM, Kearns-Jonker M Intragraft gene expression profile associated with the induction of tolerance. BMC Immunology Feb 11;9(1):5, 2008
7. Kiernan K, Harnden I, Gunthart M, Gregory C, Meisner J and Kearns-Jonker M. The anti-non-Gal xenoantibody response to xenoantigens on Gal knockout pig cells is encoded by the IGHV3-21 germline progenitor. American Journal of Transplantation 8: 1829-1839, 2008
8. Fischer-Lougheed J, Tarantal A., Shulkin I, Noboru Mitsuhashi, Kohn DB, Lee C, Kearns-Jonker M. Gene therapy to inhibit xenoantibody production using lentiviral vectors in non-human primates. Gene Therapy 14(1):49-57, 2007
9. Zahorsky-Reeves JL, Kearns-Jonker MK, Lam TL, Jackson J.R, Morris RE, Starnes VA, and Cramer DV. The xenoantibody response and immunoglobulin gene expression profile of cynomolgus monkeys transplanted with hDAF–transgenic porcine hearts Xenotransplantation 14: 135-144, 2007.
10. Mitsuhashi N, Wu G, Zhu H, Kearns-Jonker M, Cramer DV, Starnes VA, and Barr M. Rat chemokine CXCL11; Structure, tissue distribution, function and expression in cardiac transplantation models. Molecular and Cellular Biochemistry 296 (1-2):1-9, 2007
11. Kearns-Jonker M, Barteneva N, Mencel R, Hussain N, Shulkin I, Xu A., Yew M and D.V.Cramer. Use of molecular modeling and site-directed mutagenesis to define the structural basis for the immune response to carbohydrate xenoantigens BMC Immunology 8(1):3, 2007
12. Gunthart M and Kearns-Jonker M. Gene Therapy for the Induction of Chimerism and Transplant Tolerance. Current Gene Therapy 7 (6) 411-420, 2007.
13. Mitsuhashi N, Fischer-Lougheed J, Shulkin I, Kleihauer A, Kohn DB, Weinberg K, Starnes VA, and Kearns-Jonker MK. Tolerance induction by lentiviral gene therapy with a non-myeloablative regimen. Blood 107(6) 2286-93,2006.
14. Zahorsky-Reeves J., Gregory C, Cramer DV, Patanwala I, Kyles AE, Borie DC, Christe KL, Starnes VA, and Kearns-Jonker M. Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes.BMC Immunol 7(1):3, 2006.
15. Evans JM, Doki T, Fischer-Lougheed J, Davicioni E, and Kearns-Jonker M. Expression changes in tolerant murine cardiac allografts after gene therapy with a lentiviral vector expressing a1,3 galactosyltransferase. Transplantation Proceedings 38, 3172-3180, 2006.
16. Kleihauer A, Gregory CR, Borie DC, Kyles AE, Shulkin I, Patanwala I, Zahorsky-Reeves J, Starnes VA, Mullen Y, Todorov IT, and Kearns-Jonker M. Identification of the VH genes encoding xenoantibodies in non-immunosuppressed rhesus monkeys. Immunology 116: 89-102, 2005