Christopher T. Denny, M.D.

Laboratory Address:
700 Westwood Blvd
Los Angeles, CA 90095

Office Address:
10-240
CAMPUS - 175217
CA

Affiliations
Affiliations
Professor, Pediatrics, Pediatric Hematology/Oncology
Research Director, Pediatric Hematology/Oncology
Leader, Center for Translational Technologies
Member, CTSI, California NanoSystems Institute, Child Health Research, Pediatric Bone and Soft Tissue Sarcoma Program
Research Interests
Genomic mutation is a primary force in the genesis of human malignancy. Molecular isolation of genes involved in tumor-specific rearrangements has identified mechanisms of tumorigenesis and has formed a basis for studying transformation pathways of human cancers. My lab has focused on the 11;22 translocation that occurs in Ewing's sarcoma and PNET, two lethal and poorly understood pediatric cancers of presumed neural crest origin. This rearrangement fuses a previously unknown gene, termed EWS, to FLI-1, a member of the ETS family of transcription factors. We have isolated this chimeric molecule both as genomic and cDNA clones, and have shown that EWS/FLI can transform rodent fibroblast lines. This is consistent with the notion that it plays an active role in Ewing's sarcoma oncogenesis. Mutation analyses, DNA-binding studies and subcellular localization experiments have lead us to hypothesize that EWS/FLI is acting as an aberrant transcription factor that is qualitatively different from normal FLI-1. A novel method for identifying differentially expressed genes has been developed to isolate potential target genes that are modulated by EWS/FLI. This cohort of EWS/FLI regulated genes is now being analyzed with a long term goal of defining important genetic pathways that are activated during cellular transformation.
Publications
Federman Noah, Chan Jason, Nagy Jon O, Landaw Elliot M, McCabe Katelyn, Wu Anna M, Triche Timothy, Kang Hyunggyoo, Liu Bin, Marks James D, Denny Christopher T Enhanced growth inhibition of osteosarcoma by cytotoxic polymerized liposomal nanoparticles targeting the alcam cell surface receptor. Sarcoma. 2012; 2012: 126906.
Anderson Jennifer L, Denny Christopher T, Tap William D, Federman Noah Pediatric Sarcomas: Translating Molecular Pathogenesis of Disease to Novel Therapeutic Possibilities. Pediatric research. 2012; .
France Kelly A, Anderson Jennifer L, Park Ann, Denny Christopher T Oncogenic fusion protein EWS/FLI1 down-regulates gene expression by both transcriptional and posttranscriptional mechanisms. The Journal of biological chemistry. 2011; 286(26): 22750-7.
Ikeda Alan K, Judelson Dejah R, Federman Noah, Glaser Keith B, Landaw Elliot M, Denny Christopher T, Sakamoto Kathleen M ABT-869 inhibits the proliferation of Ewing Sarcoma cells and suppresses platelet-derived growth factor receptor beta and c-KIT signaling pathways. Molecular cancer therapeutics. 2010; 9(3): 653-60.
Federman Noah, Denny Christopher T Targeting liposomes toward novel pediatric anticancer therapeutics. Pediatric research. 2010; 67(5): 514-9.
Hicks Christopher M, Bandiera Glen W, Denny Christopher J Building a simulation-based crisis resource management course for emergency medicine, phase 1: Results from an interdisciplinary needs assessment survey. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2008; 15(11): 1136-43.
Potikyan Gary, France Kelly A, Carlson Marc R J, Dong Jun, Nelson Stanley F, Denny Christopher T Genetically defined EWS/FLI1 model system suggests mesenchymal origin of Ewing's family tumors. Laboratory investigation; a journal of technical methods and pathology. 2008; 88(12): 1291-302.
Potikyan Gary, Savene Rupert O V, Gaulden Julie M, France Kelly A, Zhou Zhichao, Kleinerman Eugenie S, Lessnick Stephen L, Denny Christopher T EWS/FLI1 regulates tumor angiogenesis in Ewing's sarcoma via suppression of thrombospondins. Cancer research. 2007; 67(14): 6675-84.
Ng King Pan, Potikyan Gary, Savene Rupert OV, Denny Christopher T, Uversky Vladimir N, Lee Kevin AW Multiple aromatic side chains within a disordered structure are critical for transcription and transforming activity of EWS family oncoproteins. Proc. Natl. Acad. Sci. U.S.A. 2007; 104(2): 479-84.
Kim Sungeun, Denny Christopher T, Wisdom Ron Cooperative DNA binding with AP-1 proteins is required for transformation by EWS-Ets fusion proteins. Molecular and cellular biology. 2006; 26(7): 2467-78.
Davis Ian J, Kim Jessica J, Ozsolak Fatih, Widlund Hans R, Rozenblatt-Rosen Orit, Granter Scott R, Du Jinyan, Fletcher Jonathan A, Denny Christopher T, Lessnick Stephen L, Linehan W Marston, Kung Andrew L, Fisher David E Oncogenic MITF dysregulation in clear cell sarcoma: defining the MiT family of human cancers. Cancer cell. 2006; 9(6): 473-84.
Deneen Benjamin, Hamidi Habib, Denny Christopher T Functional analysis of the EWS/ETS target gene uridine phosphorylase. Cancer research. 2003; 63(14): 4268-74.
Denny Christopher J, Steinhart Brian D, Yu Richard Improving physician flow and efficiency in the emergency department. CJEM. 2003; 5(4): 271-4.
Deneen Benjamin, Welford Scott M, Ho Thu, Hernandez Felicia, Kurland Irwin, Denny Christopher T PIM3 proto-oncogene kinase is a common transcriptional target of divergent EWS/ETS oncoproteins. Molecular and cellular biology. 2003; 23(11): 3897-908.
Ho, T. Deneen, B. Denny, C. Up-regulation of PIM3 may be necessary but not sufficient in the formation of tumors with the characteristics of Ewing's sarcoma family tumors. Journal of Investigative Medicine 2003; 51: S100-S100.
Foote Simon, Denny Christopher Construction of YAC libraries with large inserts. Current protocols in human genetics / editorial board, Jonathan L. Haines ... [et al.]. 2002; Chapter 5(4): Unit5.2.
Maris John M, Denny Christopher T Focus on embryonal malignancies. Cancer cell. 2002; 2(6): 447-50.
Morra, M. Lu, J. Poy, F. Calpe, S. Martin, M. Gullo, C. Howie, D. Denny, C. Engel, P. Eck, M. J. Terhorst, C. The "free SH2-domain" EAT-2 binds CD150-related receptors in hematopoietic cells. Faseb Journal 2002; 16(4): A321-A321.
Denny, C. Defining small round cell tumors of childhood: When is a rose really a rose. Journal of Pediatric Hematology Oncology 2001; 23(6): 338-339.
Deneen B, Denny CT Loss of p16 pathways stabilizes EWS/FLI1 expression and complements EWS/FLI1 mediated transformation. Oncogene. 2001; 20(46): 6731-41.
Arvand A, Welford S, Teitell MA, Denny CT The C-terminal domain of FLI-1 is necesary for full tumorigenic potential of the EWS/FLI1. Cancer Research. 2001; 61: 5311-17.
Welford SM, Gregg J, Chen E, Garrison D, Sorensen PH, Denny CT, Nelson SF Detection of differentially expressed genes in primary tumor tissues using representational differences analysis coupled to microarray hybridization. Nucleic acids research. 1998; 26(12): 3059-65.
May WA, Arvand A, Thompson AD, Braun BS, Wright M, Denny CT EWS/FLI1-induced Manic Fringe renders NIH 3T3 cells tumorigenic. Nature Genetics. 1997; 17: 495-498.
Anderson Jennifer L, Park Ann, Akiyama Ryan, Tap William D, Denny Christopher T, Federman Noah Evaluation of In Vitro Activity of the Class I PI3K Inhibitor Buparlisib (BKM120) in Pediatric Bone and Soft Tissue Sarcomas. PloS one. 2015; 10(9): e0133610.
Anderson Jennifer L, Titz Björn, Akiyama Ryan, Komisopoulou Evangelia, Park Ann, Tap William D, Graeber Thomas G, Denny Christopher T Phosphoproteomic profiling reveals IL6-mediated paracrine signaling within the Ewing sarcoma family of tumors. Molecular cancer research : MCR. 2014; 12(12): 1740-54.
Denny Christopher T ChIP-ping away at EWS/ETS transcription networks. Cancer cell. 2014; 26(5): 595-6.