The main research focus of our laboratory in the last 5 years has been the study of the immune system in hematological malignancies and after HSCT, as well as the development of strategies that modulate immunity and tolerance post-transplant to enhance patient survival. Donor immunity emerging post-transplant plays a pivotal role in the protection against infections, such as CMV and EBV, as well as in the development of graft versus host disease (GVHD) and graft versus leukemia (GVL) effect. All these variables impact patient survival. We are particularly interested in developing strategies that may be easily translated into the clinical setting, such as the use of donor regulatory T cells for refractory GVHD. Over the past few years, we have developed several projects in the lab, from a prospective dissection of T cell homeostasis in patients developing chronic GVHD after HSCT, to more basic projects looking at the pattern of methylation of different subtypes of regulatory T cells. All of our studies are carried out in human samples and lay the foundation for the development of novel methods to specifically modulate immune reconstitution and tumor immunity after transplant. Under the auspices of the EC Horizon 2020-funded project TREGeneration, which we coordinate, we are currently conducting a Phase I/Phase II clinical trial of donor regulatory T cells in patients with refractory chronic GVHD. At the same time, we are developing novel platforms for the expansion of different populations of regulatory T cells to be eventually employed in the clinic, such as MSC-induced and allo-specific regulatory T cells. We also maintain lines of investigation in the biology and genetic propensity for the development of invasive fungal infections, in which we have disclosed several novel findings, such as the role of PTX3 in the emergence of invasive aspergillosis. We are also evaluating genetic susceptibility to CMV infection in patient/donor pairs after hematopoietic stem cell transplantation. In 2020, we are also starting a new line of research in the field of CAR T cell therapy for hematologic neoplasms. We are particularly interested in two vectors: first, the improvement of current CAR platforms by making subtle changes in the different domains of the CAR molecule, and secondly by the development of novel and more universal receptors for the treatment of a plethora of malignant disorders. This last project is particularly ground-breaking, as by targeting non-conventional receptors in the malignant cell it has the potential to become a new therapy for many different subtypes of cancers.