Associate ProfessorAlexandra Sharland

Basic and translational research in transplantation.

Our research focuses on understanding the mechanisms which determine the fate of alloreactive T cells following antigen encounter, and the outcomes of organ or tissue transplantation. Gene transfer of donor MHC class I molecules to the recipient liver is a robust and powerful strategy for transplant tolerance induction, which is effective even in the presence of pre-existing anti-donor immunity. Tolerance induction depends on the direct recognition of intact donor MHC class I molecules, along with their endogenous peptide cargo. Recently, we have identified a number of specific peptide-MHC (pMHC) epitopes recognised by directly alloreactive T cells, and are using this information to develop methods for the detection, tracking and immunophenotyping of these cells. Cloning and sequencing the alloreactive T cell receptors (TCR) identified in this way will form the basis for detailed studies of the TCR-pMHC interaction.

Approaches we use in our research include preclinical models of transplantation and related conditions, gene transfer using adeno-ascociated viral vectors, multiparameter flow, spectral and mass cytometry, histology and immunostaining, mass spectrometry and computational analysis (via a collaboration with the immunoproteomics group at Monash), PCR, tissue culture, ex-vivo assays of T cell activation, cellular and molecular cloning.