- Regulatory T cells in organ transplantation, cancer and immune-related diseases
- T cell signalling mechanisms
- Liver transplantation for autoimmune diseases and malignancies
- Clinical and surgical aspects in kidney transplantation
- New strategies in medical and surgical treatment in pancreas transplantation for severe diabetes type I
- The use of extended criteria donors in liver transplantation
- ABO-incompatible liver transplantation
- Liver transplantation as rescue treatment after liver resections and surgical complications after liver surgery
T cell function in cancer and immune-related diseases
A major goal of our research group is to understand immunobiology of Treg suppression. We make use healthy human donor PBMCs to study invitro how Tregs supress CD4 and CD8 Teffs in contact dependent manner. Previously we have shown the importance of suppressive potency of Tregs and how Treg control the TCR signalling and susceptibility to suppression in CD4 Teffs (Chellappa et al., J Leuk Biol 2016).
Current project aims to understand the mutual interactions of Tregs and CD4/8 Teffs and to decipher the contact-dependent suppression mechanisms. We use phospho-Flowcytometry, Treanscriptomics and proteomic approach to study the mutual interactions between Tregs and Teffs. Surface shaving of suppressive Tregs leads to their loss of suppressive capacity. We are currently carrying out proteomic analysis of shaved peptides of suppressive Tregs to identify key surface receptors involved in the contact-dependent suppression. Other approaches includes, targeting Connexin 43, a gap junction protein involved in transfer of cAMP from Treg to Teffs and siRNA against Connexin 43.
Immunophenotyping Kidney, Pancreas and Liver transplant patients prior and after transplantation
Learned from the basic immunology of Tregs, our ultimate goal is to translate the key suppressive mechanisms in cancer and autoimmune settings. Transplant surgeon Dr. Einar-Martin Aandahl has access to patient’s material from kidney, pancreas and liver transplantations. Liver transplant patient’s referred mainly due to primary sclerosing cholangitis (PSC) and hepatocellular carcinoma (HCC). We aim to compare the immune signatures between cancer setting (HCC) and autoimmune setting (PSC). We have a biobank of serum, plasma and PBMCs collected prior to the transplantation and three months, six months and one year after transplantation. We currently use multicolour flow cytometry (BD Fortessa with 4 lasers) up to 20 flurochromes to immune-phenotype the PBMCs. To comprehensively analyse numerous surface antigen and intracellular cytokine/chemokines in a single sample, we want to use CytOF technology.