As a Medical Doctor and resident in Internal Medicine at the University of  Rome, Dr. Natoli began a scientific career in a clinical environment  primarily focused on viral hepatitis research. During undergraduate studies and the Internal Medicine Residency, he developed a strong interest in basic molecular mechanisms of disease, particularly inflammation and cancer. As a post-doctoral fellow at the Department of Pharmacology of the University of California, San Diego in Michael Karin’s lab (1998-2000), Dr. Natoli started working on signal transduction and transcription factors that control the expression of inflammatory genes. In 2000, he commenced research activity as an independent investigator at the Institute for Research in Biomedicine (IRB) in Switzerland. Here, the focus shifted from signaling to investigating  the mechanisms linking chromatin organization to the control of inflammatory gene expression in cells of the innate immune system, a research area that he continued and expanded after moving to the European Institute of Oncology (IEO) in Milan in 2005. The most significant contribution of Dr. Natoli's laboratory has been the elucidation of how the regulatory information contained in mammalian genomes controls the deployment of the inflammatory gene expression programs in a cell type - and stimulus-specific manner. This research has validated concepts now commonly accepted, particularly the notion that transcription factors controlling the differentiation of innate immune cells determine where transcription factors activated in response to inflammatory stimulation bind in the genome, thus establishing the foundation for cell type-specific inducible gene expression. More recently, Dr. Natoli's research has expanded to include a molecular understanding of cellular heterogeneity in human pancreatic cancer using a combination of omics and functional genomics approaches. In particular his work focuses on transcriptional mechanisms underlying the extensive loss of lineage fidelity characteristic of PDAC and accounting for the extensive plasticity of this cancer.