Although the genes that drive the development of myeloid blood cancers have largely been defined, there are currently few effective targeted treatment strategies for these diseases. The development of imatinib to treat BCR/ABL-positive chronic myeloid leukemia remains the only true success story, with the majority of targeted therapies for myeloid malignancies demonstrating unimpressive clinical activity. This illuminates the need to exploit the molecular understanding that has been gained in the last decade through cancer exome sequencing to identify novel therapeutic vulnerabilities in myeloid malignancies.
Research in the Elf Lab focuses on identifying unique molecular dependencies in myeloid blood cancers that can be targeted for therapeutic intervention, with the long-term goal of improving upon existing treatment regimens for these diseases. Current work, in the lab involves understanding the role of the unfolded protein response (UPR) in myeloproliferative neoplasms (MPN) and acute myeloid leukemia (AML). We are particularly interested in dissecting the molecular mechanisms underlying UPR activation in calreticulin (CALR)-mutated MPN and isocitrate dehydrogenase (IDH)-mutated AML, including how oncogenic signaling pathways, metabolism, and epigenetics converge on the UPR to promote cellular adaptation and survival. Using molecular, biochemical, and cellular approaches in both in vitro and in vivo models, we aim to use this mechanistic insight to develop rationally designed therapies to target the UPR in these challenging diseases.