Pier Paolo Pandolfi, MD
Harvard Medical School
The Pandolfi laboratory is dedicated to understanding the molecular genetics and mechanisms that lead to tumorigenesis and has helped to elucidate the pathogenesis of leukemias and solid tumors as well as modeling these cancers in the mouse. Throughout the years, Dr. Pandolfi and colleagues have characterized the function of the fusion oncoproteins and the genes involved in the chromosomal translocations of acute promyelocytic leukemia (APL), as well as of major tumor suppressors such as PTEN and p53, and novel cancer genes such as POKEMON. The elucidation of the molecular basis underlying APL pathogenesis has led to the development of novel and effective therapeutic strategies. As a result of these efforts, APL is now considered a curable disease. Additional novel therapeutic concepts have emerged from this work and are currently being tested in clinical trials (e.g. Gleevec and Arsenic combination trials in chronic myelogenous leukemia (CML)). Dr. Pandolfi’s team has also developed new discovery platforms using faithful mouse models of cancers (e.g. the “Mouse Hospital” and the “Co-Clinical” trial project) that not only allowed to study genetic alterations associated with the disease, but that can be used for the human/mouse Co-Clinical integrated assessment of new therapeutic modalities in Co-Clinical Trials. More recently, Dr. Pandolfi and colleagues have focused their attention on the molecular genetics of the non-coding RNA dimension of the genome. Specifically, they have presented a new theory describing how RNAs, both non-coding and protein coding, exerts their biological functions; and demonstrated the critical importance of diverse types of non-coding RNAs including miRNAs, circRNAs, pseudogenes and lincRNAs, in tumorigenesis and therapy resistance.