Nancy Zeleznik-Le, PhD

 

Nancy Zeleznik-Le, PhD

 

CHAIR, CANCER BIOLOGY
PROFESSOR, CANCER BIOLOGY; MEDICINE

Contact:
nzelezn@luc.edu 
CBCC 337

 

Research Focus Areas:              

  • MLL leukemias
  • Hematopoiesis
  • Chromatin-mediated gene regulation and epigenetics

My laboratory is interested in understanding how oncogenic MLL fusion proteins cause aggressive MLL leukemias and how this information could inform novel therapeutic approaches for this devastating cancer. Our focus is on structure-informed functional studies of the chromatin regulators MLL and the MLL fusion partners such as AF9 (MLLT3) and ENL (MLLT1) to understand their gene regulatory mechanisms. The wildtype MLL, AF9 and ENL proteins normally function as master regulators of critical gene expression pathways via chromatin epigenetic reader and writer mechanisms, whereas the oncogenic MLL fusion proteins cause misregulated expression of these same MLL target genes. We utilize a variety of complementary approaches including in vitro and in vivo leukemia models, normal hematopoietic stem and progenitor cell analyses, and advanced molecular and cellular techniques. Our research has implications for improving normal hematopoietic stem cell function and to determine mechanisms that might be amenable to therapeutic targeting of MLL leukemia.

EDUCATION:

  • BS in Microbiology and Immunology. The Ohio State University
  • PhD in Immunology / Cellular and Molecular Biology, Duke University
  • Postdoctoral fellowship, Lineberger Cancer Resarch Center, University of North Carolina Chapel Hill

SELECT PUBLICATIONS:

  • BCOR binding to MLL-AF9 is essential for leukemia via altered EYA1, SIX, and MYC activity Schmidt, CR; Achille, NJ; Kuntimaddi, A; Boulton, AM; Leach, BI; Zhang, S; Zeleznik-Le, NJ; Bushweller, JH  Blood Cancer Discovery  2020 Sep;1(2):162-177. doi: 10.1158/2643-3230.BCD-20-0036. PMID: 32954361; PMCID: PMC7497807
  • One step forward in the challenging arena of MLL-AF4 leukemia  Zeleznik-Le, NJ  Cancer Cell 2016 Nov 14;30(5):657-658. doi: 10.1016/j.ccell.2016.10.017. PMID: 27846384
  • The miR-17∼92 cluster contributes to MLL leukemia through the repression of MEIS1 competitor PKNOX1  Mian, YA; Zeleznik-Le, NJ Leukemia Research  2016 Jul;46:51-60. doi: 10.1016/j.leukres.2016.04.006. Epub 2016 Apr 16. PMID: 27123834; PMCID: PMC4899285
  • Association between early promoter-specific DNA methylation changes and outcome in older acute myeloid leukemia patients    Achille, NJ; Othus, M; Phelan, K; Zhang, S; Cooper, K; Godwin, JE;  Appelbaum, FR; Radich, JP; Erba, HP; Nand, S; Zeleznik-Le, NJ   Leukemia Research  2016 Mar;42:68-74. doi: 10.1016/j.leukres.2016.01.004. Epub 2016 Jan 15. PMID: 26818573; PMCID: PMC4779662.
  • Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di- and tri-methylation on target genes and transformation potential  Kuntimaddi, A; Achille, NJ; Thorpe, J; Lokken, AA; Singh, R; Hemenway, CS; Adli, M; Zeleznik-Le, NJ; Bushweller, JH  Cell Reports  2015 May 5;11(5):808-20. doi: 10.1016/j.celrep.2015.04.004. Epub 2015 Apr 23. PMID: 25921540; PMCID: PMC4426023.
  • Introduction to progress and promise of epigenetics for diagnosis and therapy in cancer Zeleznik-Le, NJ  Cancer Genetics  2015 May;208(5):165-6. doi: 10.1016/j.cancergen.2015.04.003. Epub 2015 Apr 14. PMID: 25981828
  • WEE1 is a validated target of the microRNA miR-17-92 cluster in leukemia  Brockway S; Zeleznik-Le NJ. Cancer Genet  2015 May;208(5):279-87. doi: 10.1016/j.cancergen.2015.01.001. Epub 2015 Jan 20. PMID: 25732734; PMCID: PMC4466047.
  • FAK mediates a compensatory survival signal parallel to PI3K-AKT in PTEN-null T-ALL cells  You, D; Xin, J; Volk, A; Wei, W; Schmidt, R; Scurti, G; Nand, S; Breuer, EK; Kuo, PC; Breslin, P; Kini AR; Nishimura MI; Zeleznik-Le NJ; Zhang J  Cell Reports  2015 Mar 31;10(12):2055-68. doi: 10.1016/j.celrep.2015.02.056. Epub 2015 Mar 19. PMID: 25801032; PMCID: PMC7001526

Nancy Zeleznik-Le Publications List