New Investigator Research Grant Program

Our research is focused on understanding the mechanisms underlying a disease named Richter transformation (RT), which represents a fatal complication of patients affected by chronic lymphocytic leukemia (CLL). CLL is a very common disorder of blood B cells (i.e., the cells within the immune systems that are responsible for antibody production), primarily affecting the elderly, with an onset at ~70 years of age. RT is a rarer disease that affects ~10% CLL patients and occurs as an aggressive transformation of CLL into lymphoma, a cancer affecting lymph nodes and related tissues. Patients with RT generally survive less than one year and are heavily resistant to most available therapies. New studies have identified genetic mutations (i.e., changes in the DNA encoding genes) typical of CLL and RT patients, but how these mutations generate changes in B cells, and how these changes lead to CLL and later transformation into RT is still undefined. Our studies aim to analyze the effect of one very prevalent RT mutation (i.e., NOTCH1) in modulating the properties of cancer cells and the surrounding immune cells – the so-called ‘tumor microenvironment’. We will perform these studies through cutting-edge technology which allows to understand the behavior of individual cells through complex bioinformatic analysis. In collaboration with clinicians, we will study samples obtained from RT patients. These studies will define fundamental mechanisms at the basis of CLL transformation and RT.