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Shannon Elf

Assistant Professor
shannonelf@uchicago.edu
Research Summary
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.
Keywords
Leukemia, Acute Myeloid, Myeloproliferative Disorders, Unfolded Protein Response, Targeted Molecular Therapies, Metabolism, Hematopoietic Malignancies, Calreticulin
Education
  • Bowdoin College, Brunswick, ME, A.B. Biology & Music, English minor 05/2003
  • Emory University, Atlanta, GA, Ph.D. Molecular & Systems Pharmacology 07/2013
  • Harvard Medical School / Brigham & Women’s Hospital, Boston, MA, Postdoctoral training Hematology 01/2019
Biosciences Graduate Program Association
Publications

  1. 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. View in: PubMed

  2. 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. View in: PubMed

  3. 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. View in: PubMed

  4. R-2-HG in AML? friend or foe? Blood Sci. 2021 Apr; 3(2):62-63. View in: PubMed

  5. Lysine acetylation restricts mutant IDH2 activity to optimize transformation in AML cells. Mol Cell. 2021 09 16; 81(18):3833-3847.e11. View in: PubMed

  6. Metabolon: a novel cellular structure that regulates specific metabolic pathways. Cancer Commun (Lond). 2021 06; 41(6):439-441. View in: PubMed

  7. JAK out of the box: myeloproliferative neoplasms--associated JAK2 V617F mutations contribute to aortic aneurysms. Haematologica. 2021 07 01; 106(7):1783-1784. View in: PubMed

  8. Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN. Blood. 2020 10 29; 136(18):2051-2064. View in: PubMed

  9. "All Our Wisdom is Stored in the Trees" - Degrading BCR-ABL with Berberis Vulgaris. Clin Cancer Res. 2020 08 01; 26(15):3899-3900. View in: PubMed

  10. Defining the requirements for the pathogenic interaction between mutant calreticulin and MPL in MPN. Blood. 2018 02 15; 131(7):782-786. View in: PubMed

  11. Tetrameric Acetyl-CoA Acetyltransferase 1 Is Important for Tumor Growth. Mol Cell. 2016 12 01; 64(5):859-874. View in: PubMed

  12. Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin. Oncogene. 2017 01 12; 36(2):254-262. View in: PubMed

  13. Mutant Calreticulin Requires Both Its Mutant C-terminus and the Thrombopoietin Receptor for Oncogenic Transformation. Cancer Discov. 2016 Apr; 6(4):368-81. View in: PubMed

  14. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation. Nat Chem. 2015 Dec; 7(12):968-79. View in: PubMed

  15. 6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling. Nat Cell Biol. 2015 Nov; 17(11):1484-96. View in: PubMed

  16. Metabolic Rewiring by Oncogenic BRAF V600E Links Ketogenesis Pathway to BRAF-MEK1 Signaling. Mol Cell. 2015 Aug 06; 59(3):345-358. View in: PubMed

  17. Distinct effects of concomitant Jak2V617F expression and Tet2 loss in mice promote disease progression in myeloproliferative neoplasms. Blood. 2015 Jan 08; 125(2):327-35. View in: PubMed

  18. Tyr-301 phosphorylation inhibits pyruvate dehydrogenase by blocking substrate binding and promotes the Warburg effect. J Biol Chem. 2014 Sep 19; 289(38):26533-26541. View in: PubMed

  19. Lysine acetylation activates 6-phosphogluconate dehydrogenase to promote tumor growth. Mol Cell. 2014 Aug 21; 55(4):552-65. View in: PubMed

  20. Tyr-94 phosphorylation inhibits pyruvate dehydrogenase phosphatase 1 and promotes tumor growth. J Biol Chem. 2014 Aug 01; 289(31):21413-22. View in: PubMed

  21. Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate the pyruvate dehydrogenase complex. Mol Cell. 2014 Feb 20; 53(4):534-48. View in: PubMed

  22. Downregulation of RUNX1/CBF? by MLL fusion proteins enhances hematopoietic stem cell self-renewal. Blood. 2014 Mar 13; 123(11):1729-38. View in: PubMed

  23. Targeting glucose metabolism in patients with cancer. Cancer. 2014 Mar 15; 120(6):774-80. View in: PubMed

  24. Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation. Nat Commun. 2013; 4:1790. View in: PubMed

  25. p90 RSK2 mediates antianoikis signals by both transcription-dependent and -independent mechanisms. Mol Cell Biol. 2013 Jul; 33(13):2574-85. View in: PubMed

  26. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell. 2012 Nov 13; 22(5):585-600. View in: PubMed

  27. Akt phosphorylates the transcriptional repressor bmi1 to block its effects on the tumor-suppressing ink4a-arf locus. Sci Signal. 2012 Oct 23; 5(247):ra77. View in: PubMed

  28. The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations. Blood. 2011 Dec 15; 118(25):6544-52. View in: PubMed

  29. p90RSK2 is essential for FLT3-ITD- but dispensable for BCR-ABL-induced myeloid leukemia. Blood. 2011 Jun 23; 117(25):6885-94. View in: PubMed

  30. p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells. J Clin Invest. 2010 Apr; 120(4):1165-77. View in: PubMed

  31. Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal. 2009 Nov 17; 2(97):ra73. View in: PubMed

  32. The p53 tumor suppressor protein is a critical regulator of hematopoietic stem cell behavior. Cell Cycle. 2009 Oct 01; 8(19):3120-4. View in: PubMed

  33. ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation. Mol Cell Biol. 2009 Jul; 29(13):3687-99. View in: PubMed

  34. Fibroblast growth factor receptor 3 associates with and tyrosine phosphorylates p90 RSK2, leading to RSK2 activation that mediates hematopoietic transformation. Mol Cell Biol. 2009 Apr; 29(8):2105-17. View in: PubMed

  35. p53 regulates hematopoietic stem cell quiescence. Cell Stem Cell. 2009 Jan 09; 4(1):37-48. View in: PubMed

  36. PU.1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. Nat Genet. 2008 Jan; 40(1):51-60. View in: PubMed

  37. Protein arginine methylation in Candida albicans: role in nuclear transport. Eukaryot Cell. 2007 Jul; 6(7):1119-29. View in: PubMed

  38. Respiratory failure due to differentiation arrest and expansion of alveolar cells following lung-specific loss of the transcription factor C/EBPalpha in mice. Mol Cell Biol. 2006 Feb; 26(3):1109-23. View in: PubMed

  39. Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation. Blood. 2005 Sep 01; 106(5):1590-600. View in: PubMed
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