Megan McNerney, MD, PhD

Assistant Professor

Department of Pathology
The University of Chicago
Knapp Center for Biomedical Discovery (KCBD)
900 E. 57th Street, Room 5128
Chicago, IL 60637
Phone: 773.834.8896

mcnerneylab.uchicago.edu

Dr. Megan McNerney received her BA at Northwestern University and M.D. and Ph.D. at the University of Chicago.  As an Immunology Ph.D. student in the lab of Vinay Kumar, M.D., M.B.B.S., she studied how natural killer cells eliminate tumor cells, and discovered a novel system of natural killer cell inhibition.  She completed her postdoctoral work in Dr. Kevin White’s laboratory within the Institute of Genomics and Systems Biology at the University of Chicago, where she characterized the genetic abnormalities in high-risk myeloid neoplasm.  Dr. McNerney is a Leukemia and Lymphoma Society Fellow and was named the 2013 Leukemia and Lymphoma Society, Illinois Chapter, Researcher of the Year.  She is a recent recipient of the Cancer Research Foundation Young Investigator Award and Riviera Country Club United-4 A Cure Award.  Other honors include the Robert W. Wissler Fellowship Award, the Leon O. Jacobson Basic Science Prize, the Robert E. Priest Pathology Merit Award, the Elaine Frank Family Fellowship for Medical Research, and the College of American Pathologists Resident Research Grant.

Clinical Interests

  • Genomic and Molecular Pathology
  • Hematopoietic Malignancy Genomics

Dr. McNerney is board-certified in Clinical Pathology and is an Attending in the Genomic and Molecular Pathology clinical diagnostic lab.  Her clinical role is identifying cancer mutations, by next-generation sequencing, to guide patient diagnosis and treatment decisions.

Research Interest

  • Myeloid Malignancy Genomics
  • Transcriptional Regulation in Hematopoiesis and Leukemogenesis

Dr. McNerney’s research focuses on the genomics of therapy-related and de novo acute myeloid leukemias (AML).  A high-risk subset of patients is unresponsive to treatment and their survival is less than a year.  Understanding the underlying genetic changes in these neoplasms is essential to identifying new therapeutic strategies for patients.  Using next-generation sequencing and other genomic approaches, Dr. McNerney determined the genetic changes that occur in high-risk myeloid leukemias.  She demonstrated that these leukemias have a distinct mutational profile.  Half of high-risk myeloid neoplasms exhibit haploinsufficiency of the CUX1 transcription factor, a tumor suppressor gene on chromosome 7 (McNerney et al. 2013, Blood 121:869).  In addition, mutations that activate the RAS signaling pathway occur at significantly higher frequency than other AMLs (McNerney et al. 2014, British Journal of Haematology, in press).  Both of these somatic changes likely cooperate to drive leukemogenesis.  Her laboratory is now leveraging this information to find new treatments for this disease, with the ultimate goal of improving patient survival.  Current approaches include identifying the aberrant transcriptional networks downstream of CUX1 loss, using genome-wide approaches such as RNA-seq and ChIP-seq.  Of particular interest is understanding the cis-regulatory logic that defines dose-sensitive CUX1 gene targets.   In addition, her lab is developing a mouse model of high-risk myeloid leukemia for pre-clinical drug testing.

Positions
Positions for graduate students and postdocs are currently available.  Please contact Megan McNerney (megan.mcnerney@uchospitals.edu).  

In the press

Selected Papers

1.         Yi, Y, McNerney, M, and Datta, SK. (2000) 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. Journal of Immunology 165: 6627-6634.

2.         Lee, KM*, McNerney, ME*, Stepp, SE, Mathew, PA, Schatzle, JD, Bennett, M, and Kumar, V. (2004) 2B4 acts as a non-MHC binding inhibitory receptor on mouse NK cells. Journal of Experimental Medicine. 199:1245-1254. *Authors contributed equally. [Commentary: SLAM family receptors regulate immunity with and without SAP-related adaptors.  Veillette, A. (2004) Journal of Experimental Medicine. 199:1175-1178. Editor’s Choice: Seeking alternative pathways. Simpson, SJ. (2004) Science. 304:1079b.]

3.         Vaidya SV, Stepp SE, McNerney ME, Lee JK, Bennett M, Lee KM, Stewart CL, Kumar V, Mathew PA. (2005) Targeted disruption of the 2B4 gene in mice reveals an in vivo role of 2B4 (CD244) in the rejection of B16 melanoma cells. Journal of Immunology. 174:800-807.

4.         McNerney, ME†, Lee KM, and Kumar, V. (2005) 2B4 (CD244) is a non-MHC binding receptor with multiple functions on natural killer cells and CD8+ T cells. Molecular Immunology. 42:489-494. †Corresponding author.

5.         Kumar, V and McNerney, ME. (2005) A new self: MHC class I independent NK cell self-tolerance.  Nature Reviews Immunology. 5:363-374. 

6.         McNerney, ME†, Guzior, D, and Kumar, V. (2005) 2B4 (CD244) – CD48 interactions provide a novel MHC class I-independent system for NK cell self-tolerance in mice. Blood. 106:1337-1340. †Corresponding author.            [Research Highlights: Natural killer cells – maintaining tolerance. Bell, E. (2005) Nature Reviews Immunology. 5:432.]

7.         McNerney, ME and Kumar, V.  (2006) The CD2 family of NK cell receptors. Colonna, M and Vivier, E eds. Current Topics in Microbiology and Immunology. 298:91-120.

8.         McNerney, ME*, Lee, KM*, Zhou, P*, Molinero, L, Mashayekhi, M, Guzior, D, Sattar, H, Kuppireddi, S, Wang, CR, Kumar, V, and Alegre, ML. (2006) Role of natural killer cell subsets in cardiac allograft rejection. American Journal of Transplantation. 6:505-513. *Authors contributed equally.

9.         Lee, KM*, Forman, J*, McNerney, ME*, Stepp, S, Kuppireddi, S, Guzior, D, Latchman, YE, Sayegh, MH, Yagita, H, Park, CK, Oh, SB, Wulfing, C, Schatzle, J, Mathew, PA, Sharpe, AH, and Kumar, V. (2006) Requirement of homotypic NK cell interactions through 2B4(CD244)/CD48 in the generation of NK effector functions. Blood. 107:3181-3188. *Authors contributed equally.

10.       Alegre, ML and McNerney, ME. (2007) NK cell subsets in allograft rejection and tolerance. Current Opinion in Organ Transplantation. 12:10-16.

11.       McNerney, ME, Baron, BW, Volchenboum, SL, Papari, M, Keith, M, Williams, K, and Richa, E. (2010) Development of warm auto- and alloantibodies in a three year-old boy with sickle cell hemoglobinopathy following his first transfusion of a single unit of red blood cells.  Blood Transfusion. 8:126-128.

12.       Godley, LA, John Cunningham, J, Eileen Dolan, ME, Stephanie Huang, RS, Gurbuxani, S, McNerney, ME, Larson, RA, Leong, H, Lussier, Y, Onel, K, Odenike, O, Stock, W, Kevin White, K, and Le Beau, MM. (2011) An integrated genomic approach to the assessment and treatment of acute myeloid leukemia. Seminars in Oncology. 38:215-224.

13.       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. (2011) Genetic pathways leading to therapy-related myeloid neoplasms. Mediterranean Journal of Hematology and Infectious Diseases. 3:e2011019.

14.       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, and White, KP†. (2013) CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia. Blood. 121:975-983. †Co-corresponding author.  [Featured on the cover. Commentary: Inside Blood – CUX1 in leukemia: dosage matters. Boultwood, J. (2013) Blood. 121:869-871.]

15.       Braegelmann, J, Dinali, M, Stricker, S, Brown, C, Zuo, Z, Khattri, A, Keck, McNerney, M, Longnecker, R, Beiging, K, Domanus, M, Alexander, K, Salgia, R, Lingen, M, Vokes, E, Cohen, E, White, K, Seiwert, T (2013) No evidence of viral genetic material in digital subtraction RNA-seq analysis of oral tongue cancers from non-smokers/non-drinkers. Oral Oncology. 49(6):525-33.

16.       Xu, J, Haigis, K, Firestone, AJ, McNerney, ME, Li, Q, Davis, E, Chen, SC, Nakitandwe, J., Downing, J, Jacks, T, Le Beau, MM, Shannon, K. (2013) Dominant Role of Oncogene Dosage and Absence of Tumor Suppressor Activity in Nras-Driven Hematopoietic Transformation. Cancer Research. 3:993-1001

17.       Heath, AP, Greenway, M, Powell, R, Spring, J, Suarez, R, Hanley, D, Bandlamudi, C, McNerney, ME, White, KP, and Grossman, RL (2014) Bionimbus: A cloud for managing, analyzing and sharing large genomics datasets. Journal of the American Medical Informatics Association. 0:1-7.

18.       McNerney ME, Brown, CD, Peterson, AL, Banerjee, M, Larson, RA, Anastasi, J, Le Beau, MM, and White, KP. (2014) The spectrum of somatic mutations in high-risk acute myeloid leukemia. British Journal of Haematology. In press. 

Pubmed link to M. McNerney's publications