RETROVIRUS-HOST INTERACTIONS AND INNATE IMMUNITY TO GENE TRANSFER
We are studying the molecular mechanisms of host-vector interplay and innate immunity in the context of hematopoietic stem and progenitor cells (HSPC) gene therapy, with particular focus on innate restriction blocks and host responses potentially triggered by the lentiviral vectors (LV) used to convey the therapeutic gene into cells. Clinical application of LV‐based HSPC gene therapy is rapidly becoming a reality. Nevertheless, LV‐mediated signaling and its potential functional consequences on HSPC biology remain poorly understood. The aim is to provide insights into how innate immune signalling may affect human HSC and hematopoietic development in vivo, with potential broad range clinical impact in the field of gene therapy.
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.