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 current treatment regimens for these diseases. Currently, our work focuses on understanding the role of the unfolded protein response (UPR) in myeloproliferative neoplasms (MPN) and acute myeloid leukemia (AML). Using molecular, biochemical, and cellular approaches in both in vitro and in vivo models, we aim to dissect the molecular mechanisms underlying UPR activation in specific subsets of MPN and AML, and to use this mechanistic insight to develop rationally designed therapies to target the UPR in these challenging diseases.
Harvard Medical School / Brigham & Women’s Hospital
Boston, MA
Postdoctoral training - Hematology
2019
Emory University
Atlanta, GA
Ph.D. - Molecular & Systems Pharmacology
2013
Bowdoin College
Brunswick, ME
A.B. - Biology & Music, English minor
2003
Whole-genome CRISPR screening identifies N-glycosylation as a genetic and therapeutic vulnerability in CALR-mutant MPNs.
Whole-genome CRISPR screening identifies N-glycosylation as a genetic and therapeutic vulnerability in CALR-mutant MPNs. Blood. 2022 09 15; 140(11):1291-1304.
PMID: 35763665
Type I but Not Type II Calreticulin Mutations Activate the IRE1a/XBP1 Pathway of the Unfolded Protein Response to Drive Myeloproliferative Neoplasms.
Type I but Not Type II Calreticulin Mutations Activate the IRE1a/XBP1 Pathway of the Unfolded Protein Response to Drive Myeloproliferative Neoplasms. Blood Cancer Discov. 2022 07 06; 3(4):298-315.
PMID: 35405004
Cellular signals converge at the NOX2-SHP-2 axis to induce reductive carboxylation in cancer cells.
Cellular signals converge at the NOX2-SHP-2 axis to induce reductive carboxylation in cancer cells. Cell Chem Biol. 2022 07 21; 29(7):1200-1208.e6.
PMID: 35429459
Lysine acetylation restricts mutant IDH2 activity to optimize transformation in AML cells.
Lysine acetylation restricts mutant IDH2 activity to optimize transformation in AML cells. Mol Cell. 2021 09 16; 81(18):3833-3847.e11.
PMID: 34289383
JAK out of the box: myeloproliferative neoplasms--associated JAK2 V617F mutations contribute to aortic aneurysms.
JAK out of the box: myeloproliferative neoplasms--associated JAK2 V617F mutations contribute to aortic aneurysms. Haematologica. 2021 07 01; 106(7):1783-1784.
PMID: 33567815
Metabolon: a novel cellular structure that regulates specific metabolic pathways.
Metabolon: a novel cellular structure that regulates specific metabolic pathways. Cancer Commun (Lond). 2021 06; 41(6):439-441.
PMID: 33939322
R-2-HG in AML? friend or foe?
R-2-HG in AML? friend or foe? Blood Sci. 2021 Apr; 3(2):62-63.
PMID: 35402830
Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN.
Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN. Blood. 2020 10 29; 136(18):2051-2064.
PMID: 32726410
"All Our Wisdom is Stored in the Trees" - Degrading BCR-ABL with Berberis Vulgaris.
"All Our Wisdom is Stored in the Trees" - Degrading BCR-ABL with Berberis Vulgaris. Clin Cancer Res. 2020 08 01; 26(15):3899-3900.
PMID: 32398325
Defining the requirements for the pathogenic interaction between mutant calreticulin and MPL in MPN.
Defining the requirements for the pathogenic interaction between mutant calreticulin and MPL in MPN. Blood. 2018 02 15; 131(7):782-786.
PMID: 29288169