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Molecular Cardiology Research Institute (MCRI)

Translational Immunology Science Center

Overview

A longstanding focus of our laboratory is to understand the cellular and molecular basis of adaptive immune responses and immunological tolerance. We have chosen to use transplantation as a model system because of the wide array of reagents available to study B and T cell immunity and tolerance in vivo, and because of the translational potential of the work. We wish to understand the role of T cell subsets in rejection, and how the response of each subset can be prevented.

We also study the development and regulation of B cells that produce natural antibodies. This work has led to an additional area of focus related to whether pre-existing natural antibody repertoires can be used to augment antigen immunogenicity and improve vaccines. Most recently, the laboratory has become interested in microRNA biology. We are examining the role of microRNAs in T cell activation, as well as how tissue injury responses are regulated by microRNAs in the context of transplantation.

Publications

D'Addio F, Yuan X, Habicht A, Williams J, Ruzek M, Iacomini J, Turka LA, Sayegh MH, Najafian N, Ansari MJ. 2010. A novel clinically relevant approach to tip the balance toward regulation in stringent transplant model. Transplantation 90: 260-269.

Godwin JG, Ge X, Stephan K, Jurisch A, Tullius SG, Iacomini J. 2010. Identification of a microRNA signature of renal ischemia reperfusion injury. Proc Natl Acad Sci U S A. 107: 14339-14344.

Jindra PT, Bagley J, Godwin JG, Iacomini J. 2010. Costimulation-dependent expression of microRNA-214 increases the ability of T cells to proliferate by targeting Pten. J Immunol. 185: 990-997.

Tian C, Yuan X, Jindra PT, Bagley J, Sayegh MH, Iacomini J. 2010. Induction of transplantation tolerance to fully mismatched cardiac allografts by T cell mediated delivery of alloantigen. Clin Immunol. 136:174-187.

Yuan X, Sayegh MH, Iacomini J. 2009. Understanding how Tregs are regulated: therapeutic implications. Transplantation 88: 1159-1160.

Yuan X, Ansari MJ, D'Addio F, Paez-Cortez J, Schmitt I, Donnarumma M, Boenisch O, Zhao X, Popoola J, Clarkson MR, Yagita H, Akiba H, Freeman GJ, Iacomini J, Turka LA, Glimcher LH, Sayegh MH. 2009. Targeting Tim-1 to overcome resistance to transplantation tolerance mediated by CD8 T17 cells. Proc Natl Acad Sci U S A. 106: 10734-10739.

Bagley J, Paez-Cortez J, Tian C, Iacomini J. 2008. Gene therapy in type 1 diabetes. Crit Rev Immunol. 28: 301-324.

Yuan X, Paez-Cortez J, Schmitt-Knosalla I, D'Addio F, Mfarrej B, Donnarumma M, Habicht A, Clarkson MR, Iacomini J, Glimcher LH, Sayegh MH, Ansari MJ. 2008.

A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy. J Exp Med. 205: 3133-3144.

Bagley J, Tian C, Iacomini J. 2008. Prevention of type 1 diabetes in NOD mice by genetic engineering of hematopoietic stem cells. Methods Mol Biol. 433: 277-285.

Paez-Cortez J, Montano R, Iacomini J, Cardier J. 2008. Liver sinusoidal endothelial cells as possible vehicles for gene therapy: a comparison between plasmid-based and lentiviral gene transfer techniques. Endothelium 15: 165-173.

Baranyi U, Linhart B, Pilat N, Gattringer M, Bagley J, Muehlbacher F, Iacomini J, Valenta R, Wekerle T. 2008. Tolerization of a type I allergic immune response through transplantation of genetically modified hematopoietic stem cells. J Immunol. 180: 8168-8175.

Benatuil L, Kaye J, Cretin N, Godwin JG, Cariappa A, Pillai S, Iacomini J. 2008. Ig knock-in mice producing anti-carbohydrate antibodies: breakthrough of B cells producing low affinity anti-self antibodies. J Immunol. 180: 3839-3848.

Tian C, Yuan X, Bagley J, Blazar BR, Sayegh MH, Iacomini J. 2008. Induction of transplantation tolerance by combining non-myeloablative conditioning with delivery of alloantigen by T cells. Clin Immunol. 127: 130-137.

Tian C, Ansari MJ, Paez-Cortez J, Bagley J, Godwin J, Donnarumma M, Sayegh MH, Iacomini J. 2007. Induction of robust diabetes resistance and prevention of recurrent type 1 diabetes following islet transplantation by gene therapy. J Immunol. 179: 6762-6769.

Bagley J, Tian C, Iacomini J. 2007. New approaches to the prevention of organ allograft rejection and tolerance induction. Transplantation 84: S38-41.

See All MCRI Publications

Researchers + Staff

Principal Investigator

John Iacommi
Professor of Pathology, Tufts University School of Medicine