Current Research
RETROVIRUS-HOST INTERACTIONS AND INNATE IMMUNITY TO GENE TRANSFER
Our research focuses on understanding the molecular mechanisms of host-vector interactions and innate immunity in hematopoietic stem and progenitor cell (HSPC) gene therapy, with a specific emphasis on identifying innate immune restriction blocks and host immune responses triggered by lentiviral vectors (LV). As LV-based HSPC gene therapy approaches clinical application, we aim to elucidate LV-mediated signaling effects on HSPC biology by a comprehensive transcriptomic and proteomic profiling to analyze gene and protein expression changes in HSPCs post-LV transduction and identify immune signaling pathways activated by LV integration.
HUMAN HEMATOPOIETIC DEVELOPMENT AND DISEASE MODELING
We focus on an ambitious and fundamental research program integrating developmental cell and molecular biology. The overarching research goal is to understand and recapitulate normal and pathological human hematopoietic development, both at the signaling and genetic level, with a particular interest in generating blood cell products to be used in the regenerative medicine framework. Most of the studies harness the potential of human pluripotent stem cells (hPSC; comprising human embryonic stem cells - hESC - and induced pluripotent stem cells - hiPSC). We aim to model hematopoietic development to understand the sequence of events that promotes the generation of hematopoietic stem cells by investigating the molecular mechanisms regulating human hematopoietic commitment and lineage specification using hPSC as well as mouse PSCs and embryos as model systems. Moroever, by exploiting hiPSCs derived from patient affected by hematopoietic disorders, we aim to identify the genetic requirements of specific critical stages of the development of the immune system and investigate the molecular mechanisms at the onset of these hematological diseases, representing the ultimate frontier of functional genetics.