Andrew Dunbar

The Dunbar lab seeks to explore the mechanisms driving clonal evolution in Myeloproliferative Neoplasms (MPNs), a rare form of chronic blood cancer. Left untreated, MPNs are lethal—occurring as a result of progressive bone marrow failure due to severe scarring (“myelofibrosis”) or evolution to an acute leukemia. Oncogenic mutations of the JAK/STAT pathway are present in the great majority of MPN patients and promote abnormal proliferation of bone marrow stem cells. While JAK2 inhibitor drugs have become a mainstay treatment, current inhibitors fail to reduce mutant allele fraction, and most patients lose response to therapy over time. The mechanisms promoting JAK inhibitor resistance are still unclear, but evidence suggests cooperating mutations in epigenetic/chromatin modifier proteins play a crucial role. We aim to utilize novel animal models of MPN together with state-of-the-art next-generation sequencing genomic/epigenomic assays of primary patient samples to further understand epigenetic mechanisms of disease progression and drug resistance in myeloproliferative neoplasms (MPNs). We hope the insights gleaned from these studies will have direct clinical/translational relevance for the development of novel therapies for patients with advanced MPN.