Areas of Interest
Dr. Platt's research focuses on the immunobiology of transplantation and related fields. The research explores mechanisms by which T cells and B cells recognize allogeneic and xenogeneic cells and the interactions of the immune system with tissues and organs that eventuate in injury. Dr. Platt was involved in the first successful efforts to overcome antibody-mediated barriers to organ transplantation. This effort led to the discovery of "accommodation," a condition in which an organ or tissues acquires resistance to immune mediated injury. Dr. Platt leads the most incisive effort aimed at discovering the molecular and cellular mechanisms of accommodation and applying those discoveries to improve the outcomes of transplantation.
Dr. Platt and Dr. Cascalho in Transplantation Biology have the leading effort in the world directed at understanding how B cells respond to foreign antigens in transplant and how these responses govern the fate of organ grafts. For example, Drs. Platt and Cascalho devised the first system for identifying, isolating and investigating B cells specific for organ transplants. They use this system to elucidate the inter-clonal and inter-clonal evolution of variable region genes in cells responding to allografts in humans and mice. Drs. Platt and Cascalho have also elucidated genomic regions that govern B cell responses, especially with respect to pathogenicity.
Dr. Platt has played a leading role in the development of the field of xenotransplantation - the transplantation of animal (in lieu of human) cells, tissues and organs for treatment of disease. His research was the first to apply genetic engineering to overcome immunological barriers to xenotransplantation. Recently the research has focused on identifying immune and non-immune hurdles to engrafting pig hepatocytes in humans and nonhuman primates for treatment of acute liver failure. Another recent focus has been on genetic engineering of large animals to facilitate engraftment of human stem cells and mature cells that could be expanded and/or differentiated to generate functioning tissues for treatment of disease.
Dr. Platt's research sometimes generates unanticipated discoveries that find applications in various fields besides transplantation. The discovery of accommodation and investigation of mechanisms underlying it have proven important not only in transplantation but in cancer immunology and infectious disease. Current efforts are aimed at devising ways to disrupt accommodation of tumors. Another such discovery concerned impact of an end product of the complement system on cell-mediated immunity. This end product amplifies T cell responses at the point of activation and effaces checkpoint inhibition. The discovery is now being adapted for treatment of various cancers and used as a target for development of new class of immunosuppressive agents for transplantation and autoimmunity. The discovery has also been used in collaboration with Dr. Cascalho in advancing a novel vaccine strategy to address highly mutable viruses, such as HIV.
Kodaira Y, Nair SK, Wrenshall LE, Gilboa E, Platt JL. Phenotypic and functional maturation of dendritic cells modulated by heparan sulfate. J Immunol 165:1599, 2000.
Dempsey LA, Brunn GJ, Platt JL. Heparanase, a potential regulator of cell-matrix interactions.Trends Biochem Sci 25:349, 2000.
Saadi S, Holzknecht RA, Patte CP, Platt JL. Endothelial cell activation by pore-forming structures: pivotal role for IL-1a. Circulation 101:1867, 2000.
Holzknecht ZE, Platt JL.The fine cytokine line between graft acceptance and rejection. Nat Med 6: 497, 2000.
Platt JL. Xenotransplantation: new risks and new gains. Nature 407:27, 2000.
Cascalho M, Platt JL. The immunological barrier to xenotransplantation. Immunity 14:437, 2001.
Cascalho M, Platt JL. Xenotransplantation and other means of organ replacement. Nat Rev Immunol1:154, 2001.
Platt JL. Knocking out xenograft rejection. Nat Biotechnol 20:231, 2002.
Johnson GB, Brunn GJ, Kodaira Y, Platt JL. Receptor-mediated monitoring of tissue well being via detection of soluble heparan sulfate by toll-like receptor 4. J Immunol 277: 8989, 2002.
Holzknecht ZE, Kuypers KL, Plummer TB, Williams J, Bustos M, Gores GJ, Brunn GJ, Platt JL. Apoptosis and cellular activation in the pathogenesis of acute vascular rejection. Circ Res 91:1135, 2002.
Johnson GB, Brunn GJ, Tang AH, Platt JL. Evolutionary clues to the functions of the toll-like family as surveillance receptors. Trends Immunol 24:19, 2003.
Ogle BM, Cascalho M, Joao CM, Taylor W, West LJ, Platt JL. Direct measurement of lymphocyte receptor diversity. Nucleic Acids Res 31:e139, 2003.
Ogle BM, Butters KA, Cascalho M, Plummer TB, Ring KR, Knudsen B, Litzow MR, Platt JL. Spontaneous fusion of cells between species yields transdifferentiation and retroviral transfer in vivo. FASEB J 18:548, 2004.
Johnson GB, Brunn GJ, Platt JL. An endogenous pathway to systemic inflammatory response syndrome (SIRS)-like responses through toll-like receptor 4. J Immunol (Cutting Edge) 172:20, 2004.
João CM, Ogle BM, Gay-Rubenstein C, Platt JL, Cascalho M. B cell-dependent TCR diversification. J Immunol 172:4709, 2004.
Johnson GB, Riggs BL, Platt JL. A genetic basis for the Adonis phenotype of low adiposity and strong bones. FASEB J 18:1282, 2004.
Koch CA, Khalpey ZI, Platt JL. Accommodation: preventing injury in transplantation and disease. J Immunol 172:5143, 2004.
Fan X, Ang A, Pollock-BarZiv SM, Dipchand AI, Ruiz P, Wilson G, Platt JL, West LJ. Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation. Nat Med 10:1227, 2004.
Brunn GB, Bungum MK, Johnson GB, Platt JL. Conditional signaling by Toll-like receptor 4. FASEB J19:872, 2005.
Kishore SP, Bungam MK, Platt JL, Brunn GJ. Selective suppression of toll-like receptor 4 activation by chemokine receptor 4. FEBS Letters 579:699, 2005.
Koch CA, Kanazawa A, Nishitai R, Knudsen BE, Ogata K, Plummer TB, Butters K, Platt JL. Intrinsic resistance of hepatocytes to complement-mediated injury. J Immunol 174:7302, 2005.
Ogle BM, Cascalho M, Platt JL. Biological implications of cell fusion. Nat Rev Mol Cell Biol 6:567, 2005.
Bischof D, Elsawa SF, Mantchev G, Yoon J, Michels GE, Nilson A, Sutor SL, Platt JL, Ansell SM, von Bulow G, Bram RJ. Selective activation of TACI by syndecan-2. Blood 107:3235, 2006.
Brunn GJ, Saadi S, Platt JL. Differential regulation of endothelial cell activation by complement and interleukin-1α. Circ Res 98:793, 2006.
Koch CA, Jordan CE, Platt JL. Complement-dependent control of teratoma formation by embryonic stem cells. J Immunol 177:4803-4809, 2006.
Brunn GJ, Platt JL. The etiology of sepsis: turned inside out. Trends Mol Med 12:10, 2006.
Ogle BM, West LJ, Driscoll DJ, Strome SE, Razonable RR, Paya CV, Cascalho M, Platt JL. Effacing of the T cell compartment by cardiac transplantation in infancy. J Immunol 176:1962, 2006.
Quiros RM, Rao G, Plate J, Harris JI, Brunnn GB, Platt JL, Gattuso P, Prinz RA, Xu X. Elevated serum heparanase-1 levels in patients with pancreatic carcinoma are associated with poor survival. Cancer106:532, 2006.
Brunn GJ, Wijdicks MF, Platt JL. Toward a modern concept of sepsis: New answers to ancient questions. Discov Med 6:11, 2006.
Nagata H, Nishitai R, Shirota C, Zhang J-L, Koch CA, Cai J, Awwad M, Schuurman H-J, Christians U, Abe M, Baranowska-Kortylewicz J, Platt JL, Fox IJ. Prolonged survival of porcine hepatocytes in cynomolgus monkeys. Gastroenterology 132:321, 2007.
Xu X, Rao G, Quiros RM, Kim AW, Miao H-Q, Brunn GJ, Platt JL, Gattuso P, Prinz RA. In vivo and in vitro degradation of heparan sulfate (HS) proteoglycans by HPR1 in pancreatic adenocarcinomas: Loss of cell surface HS suppresses fibroblast growth factor 2-mediated cell signaling and proliferation. J Biol Chem 282:2363, 2007.
Platt JL. Allophenic mice: A pillar awaiting its superstructure. J Immunol 178:4005, 2007.
AbuAttieh M, Rebrovich M, Wettstein PJ, Vuk-Pavlovic Z, Limper AH, Platt JL, Cascalho M. Fitness of cell-mediated immunity independent of repertoire diversity. J Immunol 178:2950, 2007.
Tang AH, Brunn GJ, Cascalho M, Platt JL. Endogenous pathway to SIRS, sepsis and related conditions. J Leukocyte Biol 82:282, 2007.
Koch CA, Geraldes P, Platt JL. Immunosuppression by embryonic stem cells. Stem Cells 26: 89-98, 2008.
Schmidt RL, Trejo TR, Plummer TB, Platt JL, Tang AH. The infection-induced proteolysis of PGRP-LC controls the IM.D. activation and melanization cascades in Drosophila. FASEB J 22:918-929, 2008.
Balin SJ, Ross TM, Platt JL, Cascalho M. HIV genes diversify in B cells. Curr HIV Res 6:10-18, 2008.
Brunn GJ, Saadi S, Platt JL. Constitutive repression of IL-1α in endothelial cells. Circ Res 102:823-830, 2008.
Kushwaha SS, Raichlin E, Sheinin Y, Kremers WK, Chandrasekaran K, Brunn GJ, Platt JL. Sirolimus affects cardiomyocytes to reduce left ventricular mass in heart transplant recipients. Eur Heart J29:2742-2750, 2008.
Yamanouchi K, Zhou H, Roy-Chowdhury N, Mancuso F, Liu L, Yamamoto T, Yannam GR, Enke C, Solberg TD, Adelson AB, Platt JL, Fox IJ, Roy-Chowdhury J, Guha C. Hepatic irradiation augments engraftment of donor cells following hepatocyte transplantation. Hepatology, 49(1):258-267, 2009.
Basma H, Soto-Gutiérrez A, Yannam G, Liu L, Ito R, Yamamoto T, Ellis E, Carson S, Sato SD, Muirhead D, Navarro-Álvarez N, Wong R, Platt JL, Mercer DF, Miller JD, Strom SC, Kobayashi N, Fox IJ. Differentiation, Enrichment and Transplantation of Human ES Cell-Derived Hepatocytes.Gastroenterology, 136:990-999, 2009.