Project 1: Molecular Pathogenesis and Therapy of Myeloproliferative Neoplasms
Principal Investigator: Ross Levine, PhD
Dr. Ross Levine will develop strategies that more effectively target JAK-STAT signaling than the currently available JAK1/2 inhibitors which have been approved by the FDA. He will explore how mutations in a signaling effector (JAK2) and a chromatin modulator (ASXL1) cooperate to dysregulate epigenetic/transcriptional output, alter signaling and promote disease progression. He will then evaluate how treatment with type II JAK2 inhibitors alone and in combination with epigenetic directed agents, such as an EZH2 inhibitor, are effective at depleting MPN HSCs with a specific focus on ASXL1-mutant, high risk MF.