Megan McNerney

Associate Professor
Websites
Research Summary
The McNerney lab studies the genomic changes in blood cancers with the goal of identifying therapeutic vulnerabilities. We focus on myeloid malignancies which are particularly difficult to treat. We apply a variety of functional genomics approaches and model systems to decipher changes in the cancer genome. Ongoing and available projects include studies of hematopoietic stem cell regulation, gene regulation during hematopoiesis, contiguous gene syndromes in cancer, and oncogenic signaling. Please visit our webpage for more information https://voices.uchicago.edu/mcnerneylab/
Keywords
Cancer, Myeloid Leukemia, Genomics, Transcription Factor, Hematopoiesis
Education
  • Northwestern University, Evanston, B.A. Molecular and Cellular Biology 1999
  • The University of Chicago, Chicago, PhD Immunology 2005
  • The University of Chicago , Chicago, MD Medicine 2007
  • The University of Chicago, Chicago, Residency Clinical Pathology 2010
  • The University of Chicago, Chicago, Postdoctoral Genomics and Systems Biology 2014
Biosciences Graduate Program Association
Awards & Honors
  • 1997 - Edgar Macey Scholarship for Summer Research, Northwestern University
  • 1999 - Graduation Cum Laude, Northwestern University
  • 1999 - Graduation with Departmental Honors, Biological Sciences, Northwestern University
  • 2000 - 2007 Medical Scientist Training Program, NIH
  • 2003 - Elaine Frank Family Fellowship for Medical Research, MSTP, University of Chicago
  • 2004 - Doolittle-Harrison Travel Fellowship, University of Chicago
  • 2005 - Robert E. Priest Pathology Merit Award, Department of Pathology, University of Chicago
  • 2006 - Committee on Immunology Best PhD Thesis Award, University of Chicago
  • 2006 - Honorable Mention Best PhD Dissertation Award, Biological Sciences, University of Chicago
  • 2007 - Leon Jacobson Prize for Senior Scientific Presentation, Pritzker School of Medicine
  • 2009 - Resident Research Grant, College of American Pathologists
  • 2010 - Robert W. Wissler Fellowship Award, Department of Pathology
  • 2011 - Leukemia and Lymphoma Society Fellow Award
  • 2013 - Cancer Research Foundation Young Investigator Award
  • 2013 - Evans Travel Award, FASEB Hematologic Malignancies Science Research Conference
  • 2013 - Leukemia and Lymphoma Society, Illinois Chapter Researcher of the Year
  • 2014 - “V” Foundation in Cancer Research Scholar Award
  • 2015 - Nachman Fellow, Dept. of Pediatrics Hematology-Oncology
  • 2017 - American Society of Hematology Junior Faculty Scholar Award
  • 2019 - American Cancer Society Research Scholar Award
  • 2020 - Faculty Award for Excellence in Graduate Teaching and Mentoring
Publications
  1. Jotte MRM, McNerney ME. The significance of CUX1 and chromosome 7 in myeloid malignancies. Curr Opin Hematol. 2022 03 01; 29(2):92-102. View in: PubMed

  2. Baeten JT, Liu W, Preddy IC, Zhou N, McNerney ME. CRISPR screening in human hematopoietic stem and progenitor cells reveals an enrichment for tumor suppressor genes within chromosome 7 commonly deleted regions. Leukemia. 2022 05; 36(5):1421-1425. View in: PubMed

  3. Krishnan M, Senagolage MD, Baeten JT, Wolfgeher DJ, Khan S, Kron SJ, McNerney ME. Genomic studies controvert the existence of the CUX1 p75 isoform. Sci Rep. 2022 01 07; 12(1):151. View in: PubMed

  4. Ludwig LM, Hawley KM, Banks DB, Thomas-Toth AT, Blazar BR, McNerney ME, Leverson JD, LaBelle JL. Venetoclax imparts distinct cell death sensitivity and adaptivity patterns in T cells. Cell Death Dis. 2021 10 27; 12(11):1005. View in: PubMed

  5. Imgruet MK, Lutze J, An N, Hu B, Khan S, Kurkewich J, Martinez TC, Wolfgeher D, Gurbuxani SK, Kron SJ, McNerney ME. Loss of a 7q gene, CUX1, disrupts epigenetically driven DNA repair and drives therapy-related myeloid neoplasms. Blood. 2021 09 02; 138(9):790-805. View in: PubMed

  6. Imgruet MK, Lutze J, An NN, Hu B, Khan S, Kurkewich J, Martinez TC, Wolfgeher DJ, Gurbuxani S, Kron SJ, McNerney ME. Loss of a 7q gene, CUX1, disrupts epigenetic-driven DNA repair and drives therapy-related myeloid neoplasms. Blood. 2021 May 26. View in: PubMed

  7. Stoddart A, Wang J, Fernald AA, Davis EM, Johnson CR, Hu C, Cheng JX, McNerney ME, Le Beau MM. Cytotoxic Therapy-Induced Effects on Both Hematopoietic and Marrow Stromal Cells Promotes Therapy-Related Myeloid Neoplasms. Blood Cancer Discov. 2020 07; 1(1):32-47. View in: PubMed

  8. Cahill KE, Karimi YH, Karrison TG, Jain N, Green M, Weiner H, Fulton N, Kadri S, Godley LA, Artz AS, Liu H, Thirman MJ, Le Beau MM, McNerney ME, Segal J, Larson RA, Stock W, Odenike O. A phase 1 study of azacitidine with high-dose cytarabine and mitoxantrone in high-risk acute myeloid leukemia. Blood Adv. 2020 02 25; 4(4):599-606. View in: PubMed

  9. McNerney ME, Le Beau MM. The Harmful Consequences of Increased Fitness in Hematopoietic Stem Cells. Cell Stem Cell. 2018 11 01; 23(5):634-635. View in: PubMed

  10. Kang W, Kadri S, Puranik R, Wurst MN, Patil SA, Mujacic I, Benhamed S, Niu N, Zhen CJ, Ameti B, Long BC, Galbo F, Montes D, Iracheta C, Gamboa VL, Lopez D, Yourshaw M, Lawrence CA, Aisner DL, Fitzpatrick C, McNerney ME, Wang YL, Andrade J, Volchenboum SL, Furtado LV, Ritterhouse LL, Segal JP. System for Informatics in the Molecular Pathology Laboratory: An Open-Source End-to-End Solution for Next-Generation Sequencing Clinical Data Management. J Mol Diagn. 2018 07; 20(4):522-532. View in: PubMed

  11. An N, Khan S, Imgruet MK, Gurbuxani SK, Konecki SN, Burgess MR, McNerney ME. Gene dosage effect of CUX1 in a murine model disrupts HSC homeostasis and controls the severity and mortality of MDS. Blood. 2018 06 14; 131(24):2682-2697. View in: PubMed

  12. McNerney ME, Godley LA, Le Beau MM. Therapy-related myeloid neoplasms: when genetics and environment collide. Nat Rev Cancer. 2017 08 24; 17(9):513-527. View in: PubMed

  13. Arthur RK, An N, Khan S, McNerney ME. The haploinsufficient tumor suppressor, CUX1, acts as an analog transcriptional regulator that controls target genes through distal enhancers that loop to target promoters. Nucleic Acids Res. 2017 Jun 20; 45(11):6350-6361. View in: PubMed

  14. Stricker TP, Brown CD, Bandlamudi C, McNerney M, Kittler R, Montoya V, Peterson A, Grossman R, White KP. Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression. PLoS Genet. 2017 03; 13(3):e1006589. View in: PubMed

  15. Kadri S, Long BC, Mujacic I, Zhen CJ, Wurst MN, Sharma S, McDonald N, Niu N, Benhamed S, Tuteja JH, Seiwert TY, White KP, McNerney ME, Fitzpatrick C, Wang YL, Furtado LV, Segal JP. Clinical Validation of a Next-Generation Sequencing Genomic Oncology Panel via Cross-Platform Benchmarking against Established Amplicon Sequencing Assays. J Mol Diagn. 2017 01; 19(1):43-56. View in: PubMed

  16. Alegre ML, McNerney ME. Natural killer cell subsets in allograft rejection and tolerance. Curr Opin Organ Transplant. 2007 Feb; 12(1):10-16. View in: PubMed

  17. Stoddart A, Qian Z, Fernald AA, Bergerson RJ, Wang J, Karrison T, Anastasi J, Bartom ET, Sarver AL, McNerney ME, Largaespada DA, Le Beau MM. Retroviral insertional mutagenesis identifies the del(5q) genes, CXXC5, TIFAB and ETF1, as well as the Wnt pathway, as potential targets in del(5q) myeloid neoplasms. Haematologica. 2016 06; 101(6):e232-6. View in: PubMed

  18. Zhao Z, Chen CC, Rillahan CD, Shen R, Kitzing T, McNerney ME, Diaz-Flores E, Zuber J, Shannon K, Le Beau MM, Spector MS, Kogan SC, Lowe SW. Cooperative loss of RAS feedback regulation drives myeloid leukemogenesis. Nat Genet. 2015 May; 47(5):539-43. View in: PubMed

  19. Wang X, Fu AQ, McNerney ME, White KP. Widespread genetic epistasis among cancer genes. Nat Commun. 2014 Nov 19; 5:4828. View in: PubMed

  20. Voce DJ, Schmitt AM, Uppal A, McNerney ME, Bernal GM, Cahill KE, Wahlstrom JS, Nassiri A, Yu X, Crawley CD, White KP, Onel K, Weichselbaum RR, Yamini B. Nfkb1 is a haploinsufficient DNA damage-specific tumor suppressor. Oncogene. 2015 May 21; 34(21):2807-13. View in: PubMed

  21. McNerney ME, Brown CD, Peterson AL, Banerjee M, Larson RA, Anastasi J, Le Beau MM, White KP. The spectrum of somatic mutations in high-risk acute myeloid leukaemia with -7/del(7q). Br J Haematol. 2014 Aug; 166(4):550-6. View in: PubMed

  22. Heath AP, Greenway M, Powell R, Spring J, Suarez R, Hanley D, Bandlamudi C, McNerney ME, White KP, Grossman RL. Bionimbus: a cloud for managing, analyzing and sharing large genomics datasets. J Am Med Inform Assoc. 2014 Nov-Dec; 21(6):969-75. View in: PubMed

  23. Xu J, Haigis KM, Firestone AJ, McNerney ME, Li Q, Davis E, Chen SC, Nakitandwe J, Downing J, Jacks T, Le Beau MM, Shannon K. Dominant role of oncogene dosage and absence of tumor suppressor activity in Nras-driven hematopoietic transformation. Cancer Discov. 2013 Sep; 3(9):993-1001. View in: PubMed

  24. Brägelmann J, Dagogo-Jack I, El Dinali M, Stricker T, Brown CD, Zuo Z, Khattri A, Keck M, McNerney ME, Longnecker R, Bieging K, Kocherginsky M, Alexander K, Salgia R, Lingen MW, Vokes EE, White KP, Cohen EE, Seiwert TY. Oral cavity tumors in younger patients show a poor prognosis and do not contain viral RNA. Oral Oncol. 2013 Jun; 49(6):525-33. View in: PubMed

  25. McNerney ME, Brown CD, Wang X, Bartom ET, Karmakar S, Bandlamudi C, Yu S, Ko J, Sandall BP, Stricker T, Anastasi J, Grossman RL, Cunningham JM, Le Beau MM, White KP. CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia. Blood. 2013 Feb 07; 121(6):975-83. View in: PubMed

  26. Stoddart A, McNerney ME, Bartom E, Bergerson R, Young DJ, Qian Z, Wang J, Fernald AA, Davis EM, Larson RA, White KP, Le Beau MM. Genetic pathways leading to therapy-related myeloid neoplasms. Mediterr J Hematol Infect Dis. 2011; 3(1):e2011019. View in: PubMed

  27. Godley LA, Cunningham J, Dolan ME, Huang RS, Gurbuxani S, McNerney ME, Larson RA, Leong H, Lussier Y, Onel K, Odenike O, Stock W, White KP, Le Beau MM. An integrated genomic approach to the assessment and treatment of acute myeloid leukemia. Semin Oncol. 2011 Apr; 38(2):215-24. View in: PubMed

  28. McNerney ME, Baron BW, Volchenboum SL, Papari M, Keith M, Williams K, Richa E. Development of warm auto- and allo-antibodies in a 3-year old boy with sickle cell haemoglobinopathy following his first transfusion of a single unit of red blood cells. Blood Transfus. 2010 Apr; 8(2):126-8. View in: PubMed

  29. McNerney ME, Lee KM, Zhou P, Molinero L, Mashayekhi M, Guzior D, Sattar H, Kuppireddi S, Wang CR, Kumar V, Alegre ML. Role of natural killer cell subsets in cardiac allograft rejection. Am J Transplant. 2006 Mar; 6(3):505-13. View in: PubMed

  30. McNerney ME, Kumar V. The CD2 family of natural killer cell receptors. Curr Top Microbiol Immunol. 2006; 298:91-120. View in: PubMed

  31. Lee KM, Forman JP, McNerney ME, Stepp S, Kuppireddi S, Guzior D, Latchman YE, Sayegh MH, Yagita H, Park CK, Oh SB, Wülfing C, Schatzle J, Mathew PA, Sharpe AH, Kumar V. Requirement of homotypic NK-cell interactions through 2B4(CD244)/CD48 in the generation of NK effector functions. Blood. 2006 Apr 15; 107(8):3181-8. View in: PubMed

  32. McNerney ME, Guzior D, Kumar V. 2B4 (CD244)-CD48 interactions provide a novel MHC class I-independent system for NK-cell self-tolerance in mice. Blood. 2005 Aug 15; 106(4):1337-40. View in: PubMed

  33. Kumar V, McNerney ME. A new self: MHC-class-I-independent natural-killer-cell self-tolerance. Nat Rev Immunol. 2005 May; 5(5):363-74. View in: PubMed

  34. Vaidya SV, Stepp SE, McNerney ME, Lee JK, Bennett M, Lee KM, Stewart CL, Kumar V, Mathew PA. Targeted disruption of the 2B4 gene in mice reveals an in vivo role of 2B4 (CD244) in the rejection of B16 melanoma cells. J Immunol. 2005 Jan 15; 174(2):800-7. View in: PubMed

  35. McNerney ME, Lee KM, Kumar V. 2B4 (CD244) is a non-MHC binding receptor with multiple functions on natural killer cells and CD8+ T cells. Mol Immunol. 2005 Feb; 42(4):489-94. View in: PubMed

  36. Lee KM, McNerney ME, Stepp SE, Mathew PA, Schatzle JD, Bennett M, Kumar V. 2B4 acts as a non-major histocompatibility complex binding inhibitory receptor on mouse natural killer cells. J Exp Med. 2004 May 03; 199(9):1245-54. View in: PubMed

  37. Yi Y, McNerney M, Datta SK. Regulatory defects in Cbl and mitogen-activated protein kinase (extracellular signal-related kinase) pathways cause persistent hyperexpression of CD40 ligand in human lupus T cells. J Immunol. 2000 Dec 01; 165(11):6627-34. View in: PubMed