Dr. Caplen was awarded her Ph.D. from the University of London (Kings College Hospital Medical School) for studies on the genetics of type I diabetes and its complications. Dr. Caplen's Postdoctoral training began at St Mary's Hospital Medical School, Imperial College, where she focused on the development of gene therapy approaches for cystic fibrosis (CF) during which she was involved in some of the first pre-clinical and clinical studies of cationic lipid mediated gene therapy for CF. In 1996, Dr. Caplen came to the National Human Genome Research Institute (NHGRI) at NIH as a Visiting Fellow, where she initially conducted studies investigating hybrid viral vector systems for the delivery of genes. It was while at NHGRI that Dr. Caplen developed a research interest in the newly identified gene silencing mechanism, RNA interference (RNAi) leading to her studies that help establish the presence of RNAi in mammalian cells. Dr. Caplen joined CCR, NCI in 2004 as a Senior Scientist, where she pioneered approaches for exploiting RNAi to investigate cancer biology and treatment and helped establish a trans-NIH facility for genome-wide RNAi screening. Dr. Caplen was appointed a Tenure-Track Investigator in CCR’s Genetics Branch in January 2016. Her current research focuses on using functional genetic methods to interrogate specific aspects of the genetic, transcriptional, and signaling alterations observed in cancers driven by fusion oncogenes.
Articles1
- (2019). Fusion transcripts: Unexploited vulnerabilities in cancer?. Wiley Interdisciplinary Reviews-RNA.
Academic Articles72
- (2020). Cancer biology functional genomics: From small RNAs to big dreams. MOLECULAR CARCINOGENESIS.
- (2020). CDK9 Blockade Exploits Context-dependent Transcriptional Changes to Improve Activity and Limit Toxicity of Mithramycin for Ewing Sarcoma. MOLECULAR CANCER THERAPEUTICS. 19(5), 1183-1196.
- (2019). Fusion transcripts: Unexploited vulnerabilities in cancer?. Wiley Interdisciplinary Reviews-RNA.
- (2019). HNRNPH1-dependent splicing of a fusion oncogene reveals a targetable RNA G-quadruplex interaction. RNA. 25(12), 1731-1750.
- (2019). MAP kinase and autophagy pathways cooperate to maintain RAS mutant cancer cell survival. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 116(10), 4508-4517.
- (2018). EWS-FLI1 reprograms the metabolism of Ewing sarcoma cells via positive regulation of glutamine import and serine-glycine biosynthesis. MOLECULAR CARCINOGENESIS. 57(10), 1342-1357.
- (2017). BRD4 facilitates DNA damage response and represses CBX5/Heterochromatin protein 1 (HP1). 8(31), 51402-51415.
- (2016). Functional Genomic Screening Reveals Splicing of the EWS-FLI1 Fusion Transcript as a Vulnerability in Ewing Sarcoma. Cell Reports. 14(3), 598-610.
- (2016). Identification of therapeutic targets applicable to clinical strategies in ovarian cancer. BMC CANCER. 16,
- (2015). Targeting MPS1 Enhances Radiosensitization of Human Glioblastoma by Modulating DNA Repair Proteins. MOLECULAR CANCER RESEARCH. 13(5), 852-862.
- (2014). Identification and validation of genes with expression patterns inverse to multiple metastasis suppressor genes in breast cancer cell lines. CLINICAL & EXPERIMENTAL METASTASIS. 31(7), 771-786.
- (2014). Loss-of-function RNAi screens in breast cancer cells identify AURKB, PLK1, PIK3R1, MAPK12, PRKD2, and PTK6 as sensitizing targets of rapamycin activity. CANCER LETTERS. 354(2), 336-347.
- (2014). Selective targeting of KRAS-Mutant cells by miR-126 through repression of multiple genes essential for the survival of KRAS-Mutant cells. Oncotarget. 5(17), 7635-7650.
- (2013). Genetic Amplification of the NOTCH Modulator LNX2 Upregulates the WNT/beta-Catenin Pathway in Colorectal Cancer. CANCER RESEARCH. 73(6), 2003-2013.
- (2013). Inhibition of polo-like kinase 1 in glioblastoma multiforme induces mitotic catastrophe and enhances radiosensitisation. EUROPEAN JOURNAL OF CANCER. 49(14), 3020-3028.
- (2012). p53-dependent Induction of PVT1 and miR-1204. JOURNAL OF BIOLOGICAL CHEMISTRY. 287(4), 2509-2519.
- (2011). A genomic strategy for the functional validation of colorectal cancer genes identifies potential therapeutic targets. INTERNATIONAL JOURNAL OF CANCER. 128(5), 1069-1079.
- (2011). Identification of the receptor tyrosine kinase AXL in breast cancer as a target for the human miR-34a microRNA. BREAST CANCER RESEARCH AND TREATMENT. 130(2), 663-679.
- (2011). RNAi Screening Identifies TAK1 as a Potential Target for the Enhanced Efficacy of Topoisomerase Inhibitors. CURRENT CANCER DRUG TARGETS. 11(8), 976-986.
- (2010). Identification of WEE1 as a potential molecular target in cancer cells by RNAi screening of the human tyrosine kinome. BREAST CANCER RESEARCH AND TREATMENT. 122(2), 347-357.
- (2009). Cellular Inhibition of Checkpoint Kinase 2 (Chk2) and Potentiation of Camptothecins and Radiation by the Novel Chk2 Inhibitor PV1019 [7-Nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. 331(3), 816-826.
- (2009). Implication of Checkpoint Kinase-dependent Up-regulation of Ribonucleotide Reductase R2 in DNA Damage Response. JOURNAL OF BIOLOGICAL CHEMISTRY. 284(27), 18085-18095.
- (2008). Allele-specific silencing of the dominant disease allele in sialuria by RNA interference. FASEB JOURNAL. 22(11), 3846-3852.
- (2008). Single-step doxorubicin-selected cancer cells overexpress the ABCG2 drug transporter through epigenetic changes. BRITISH JOURNAL OF CANCER. 98(9), 1515-1524.
- (2008). The identification of microRNAs in a genomically unstable region of human chromosome 8q24. MOLECULAR CANCER RESEARCH. 6(2), 212-221.
- (2007). Applications of RNA interference in mammalian systems. Annual Review of Genomics and Human Genetics. 8, 81-108.
- (2007). Multiplexing siRNAs to compress RNAi-based screen size in human cells. NUCLEIC ACIDS RESEARCH. 35(8),
- (2006). Asparagine synthetase as a causal, predictive biomarker for L-asparaginase activity in ovarian cancer cells. MOLECULAR CANCER THERAPEUTICS. 5(11), 2613-2623.
- (2006). Inefficient cationic lipid-mediated siRNA and antisense oligonucleotide transfer to airway epithelial cells in vivo. RESPIRATORY RESEARCH. 7,
- (2006). Selective toxicity of NSC73306 in MDR1-positive cells as a new strategy to circumvent multidrug resistance in cancer. CANCER RESEARCH. 66(9), 4808-4815.
- (2006). Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. CANCER CELL. 9(3), 189-198.
- (2005). Efficient delivery of RNA interference effectors via in vitro-packaged SV40 pseudovirions. HUMAN GENE THERAPY. 16(9), 1110-1115.
- (2005). Kinase-independent functions for Itk in TCR-induced regulation of Vav and the actin cytoskeleton. JOURNAL OF IMMUNOLOGY. 174(3), 1385-1392.
- (2004). Gene therapy progress and prospects. Downregulating gene expression: the impact of RNA interference. GENE THERAPY. 11(16), 1241-1248.
- (2004). In situ generation of pseudotyped retroviral progeny by adenovirus-mediated transduction of tumor cells enhances the killing effect of HSV-tk suicide gene therapy in vitro and in vivo. JOURNAL OF GENE MEDICINE. 6(3), 288-299.
- (2004). Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 101(7), 1892-1897.
- (2003). Short interfering RNA (siRNA)-mediated RNA interference (RNAi) in human cells. Annals of the New York Academy of Sciences. 1002, 56-62.