“Biology and Therapeutic Targeting of Mutant Calreticulin in Myeloproliferative Neoplasms”
Somatic mutations in celreticulin (CALR)are frequent and disease-initiating in myeloproliferative neoplasms (MPN). Dr. Mullally’s laboratory recently elucidated the mechanism by which mutant CALR is oncogenic and induces MPN. Building on this work and guided by strong preliminary data they have generated, she will now identify unique molecular vulnerabilities in CALR-mutant MPN that arise as a result of (i) the pathogenic binding interaction of mutant CALR with MPL and (ii) the differential protein-protein binding interactions of mutant CALR. Dr. Mullally will exploit this information to target unique molecular vulnerabilities in CALR-mutant MPN stem cells to achieve definitive cure.