Nancy Zeleznik-Le, PhD
Dr. Zeleznik-Le received her Ph.D. (Cellular and Molecular Biology/Immunology) from Duke University in 1988. She continued her training as a postdoctoral fellow at the Lineberger Cancer Center, University of North Carolina-Chapel Hill in the laboratory of Dr. Jenny Ting, working on MHC Class II gene regulation. In 1991, Dr. Zeleznik-Le became a Research Associate (Instructor) and then in 1993, a Research Associate (Assistant Professor) at the University of Chicago, working with Dr. Janet Rowley. She started her work on the Mixed Lineage Leukemia (MLL) gene and protein while at the University of Chicago. In 1999, she joined the faculty at Loyola University Medical Center as an Assistant Professor in the Hematological Malignancies Program. Dr. Zeleznik-Le holds a primary appointment in the Department of Medicine, and has adjunct appointments in two graduate programs, the Molecular Biology Program and the Molecular and Cellular Biochemistry Program. In 2003, Dr. Zeleznik-Le was promoted to Associate Professor, tenured in 2005 and promoted to Professor in 2009.
Dr. Zeleznik-Le's research interest is focused on the MLL protein, and on MLL fusion proteins that cause leukemia. MLL is involved in the proper maintenance of expression of downstream target genes, including genes of the HOX cluster. How MLL functions to help maintain proper expression of target genes is not well understood, but it involves epigenetic mechanisms acting at the level of chromatin. One focus of her work is to identify chromatin changes that are mediated by MLL and MLL fusion proteins. This also includes studies to understand how proteins that interact with MLL compete and /or synergize to mediate these effects, the specific non-methyl-CpG DNA binding activity of MLL, and the role of post-translational modifications of MLL on its function. Another main focus of her research utilizes in vitro and in vivo murine models of MLL leukemia to dissect critical functions required for immortalization and leukemogenesis. Questions addressed concern hematopoietic cell lineage commitment, and specificity of MLL and partner gene functional domains for immortalization capability. One of the research goals is to identify functions which would be amendable to novel therapy development.
Dr. Zeleznik-Le is the author of over 50 publications. She is active in training graduate students and fellows, both as a teacher and as a research mentor. She is involved in the Southwest Oncology Group (SWOG) clinical trials laboratory corelate studies. Her research is supported by grants from the National Institutes of Health.
- Mian YA, Zeleznik-Le NJ. MicroRNAs in leukemias: emerging diagnostic tools and therapeutic targets. Curr. Drug Targets 11:801-11, 2010.
- Chang MJ, Wu H, Achille NJ, Reisenauer MR, Chou CW, Zeleznik-Le NJ, Hemenway CS, Zhang W. Histone H3 lysine 79 methyltransferase Dot1 is required for immortalization by MLL oncogenes. Cancer Res, 70:10234-42, 2010, PMID 21159644.
- Birch NW, Zeleznik-Le NJ. Glycogen synthase kinase-3 and leukemia: restoring the balance. Cancer Cell 17:529-31, 2010. PMID: 20541696.
- Mi S, Li Z, Chen P, He C, Cao D, Elkahloun A, Lu J, Pelloso LA, Wunderlich M, Huang H, Luo RT, Sun M, He M, Neilly MB, Zeleznik-Le NJ, Thirman MJ, Mulloy JC, Liu PP, Rowley JD, Chen J. Aberrant overexpression and function of the miR-17-92 cluster in MLL-rearranged acute leukemia. Proc. Natl. Acad. Sci. USA, 107:3710-5, 2010. PMID: 20133587: PMC2840429
- Popovic R, Riesbeck LE, Velu CS, Chaubey A, Zhang J, Achille NJ, Erfurth FE, Eaton K, Lu J, Grimes HL, Chen J, Rowley JD, Zeleznik-Le NJ. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization. Blood 113:3314, 2009.
- Chen J, Santillan DL, Koonce M, Wei W, Luo R, Thirman MJ, Zeleznik-Le NJ, Diaz MO. Loss of MLL PHD-finger 3 is necessary for MLL-ENL-induced hematopoietic stem cell immortalization. Cancer Res, 68:6199-207, 2008.
- Cierpicki T, Risner LE, Grembecka J, Lukasik S, Popovic R, Omonkowska M, Shultis DS, Zeleznik-Le NJ, Bushweller JH. Structure of the MLL CXXC domain-DNA complex and its functional role in MLL-AF9 leukemia, Nat Struct Mol Bio, 17:62-68, 2010. published online 13 December 2009; doi:10.1038/nsmb.1714. PMID: 20010842. PMCID 2908503
- Erfurth FE, Popovic R, Grembecka J, Cierpicki T, Theisler C, Xia Z-B, Stuart T, Diaz M, Bushweller JH, Zeleznik-Le NJ. MLL protects CpG clusters from methylation within the Hoxa9 gene, maintaining transcript expression. Proc. Natl Acad Sci USA, 105:7517-7522, 2008.
- Popovic R, Erfurth FE, and Zeleznik-Le NJ. Transcriptional Complexity of the HOXA9 Locus. Blood Cells, Mol Dis., 40: 156-59, 2008
- Baron BW, Zeleznik-Le NJ, Baron MJ, Theisler C, Huo D, Krasowski MD, Thirman MJ, Perrella MA, Baron RM, Baron JM. Repression of the programmed cell death-2 (PDCD2) gene by BCL6: implications for the pathogenesis of human B- and T-cell lymphomas. Proc. Natl. Acad. Sci. USA 104:7449-54, 2007.
- Santillan DA, Theisler CM, Ryan AS, Stuart T, Zhou MM, Alkan S, Zeleznik-Le NJ. Bromodomain and Histon acetyltransferase domain specificities control MLL leukemia phenotype. Cancer Res 66: 10032-9, 2006.
- Zeleznik-Le, NJ. Leukemia RNAi: harnessing the killer within. Blood 106: 3336-3337, 2005.
- Xia, Z-B, Popovic, R, Chen, J, Theisler, C, Lorenz, T, Santillan, DA, Erfurth, F, Diaz, MO, Zeleznik-Le, NJ. The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression. Proc. Natl Acad Sci USA 102:14028-33, 2005.
- Popovic R, Zeleznik-Le NJ. MLL: How complex does it get? J Cell Biochem. 95(2):234-42, 2005.
- Mujtaba S, He Y, Zeng, L, Yan S, Plotnikova O, Sanchez R, Zeleznik-Le, NJ, Ronai Z, Zhou MM. Structural mechanism of the bromodomain of coactivator CBP in p53 transcriptional activation. Mol. Cell. 13:251-263, 2004.
- MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein. PNAS, 100(14):8342-8347, 2003.
- Chromatin-related properties of CBP fused to MLL generate a myelodysplastic-like syndrome that evolves into myeloid leukemia. The EMBO Journal, 19:4655-4664, 2000.
- MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16) (q23;p13.3). Proc Natl Acad Sci, 94:8732-8737, 1997.
- 11q23 translocations split the “AT-hook” cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. Proc Natl Acad Sci, 91:10610-10614, 1994.