Natasha J. Caplen, Ph.D.

Natasha J. Caplen, Ph.D.
Investigator
Head, Functional Genetics Section

Dr. Caplen co-discovered RNA interference (RNAi) in mammalian cells and has pioneered approaches for exploiting this gene regulatory mechanism to investigate cancer biology and treatment. Dr. Caplen applies the perturbations induced by RNA- or DNA-based technologies to interrogate specific aspects of the genetic, transcriptional, and cell-signaling alterations observed in cancer cells. These functional genetic approaches will be used to enhance our understanding of the mechanistic basis of cancer and to discover new cancer treatment strategies. Current studies are focused on the functional genetic analysis of cancers driven by fusion oncogenes.

Areas of Expertise
Functional genetics, RNA interference (RNAi), RNAi screening, Regulation of gene expression

Contact Info

Natasha J. Caplen, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 37, Room 6128A
Bethesda, MD 20892
Ph: 240-760-7366
ncaplen@mail.nih.gov

Technological advances have revolutionized the genome-scale profiling of DNA copy number and sequence, DNA and chromatin modification, and gene expression and have substantially enhanced our understanding of the molecular changes that underlie many cancers. However, functionalizing these findings in a systematic manner remains a challenge. To address this challenge I, and others, developed experimental strategies for the discovery and elucidation of gene function by exploiting the RNA interference (RNAi) gene silencing mechanism to generate loss-of-function (LOF) phenotypes. My research interests build on my experience in the nucleic acid delivery/gene therapy research field, my work on the RNAi mechanism (including studies establishing the existence of RNAi in mammalian cells), and my independent and collaborative endeavors developing RNAi based analysis and screening approaches for the study of gene function.

My laboratory uses functional genetic approaches induced by RNAi and other DNA or RNA-based technologies to interrogate specific aspects of the genetic, transcriptional, and cell-signaling alterations observed in cancer cells. Current research is focused on the development of new treatment strategies for cancers driven by fusion oncoproteins. Fusion or chimeric oncoproteins represent a unique vulnerability as they are only expressed within tumor cells. However, little is known about how tumor cells co-opt cellular processes to express, from rearranged DNA, an in-frame fusion transcript encoding a chimeric functional protein and so we are using functional genetic approaches to identify genes required for the expression or activity of fusion oncoproteins. This work will further our understanding of how the expression of this important class of cancer oncogenes is regulated and how they may be optimally targeted.

 

Scientific Focus Areas:
Cancer Biology, Genetics and Genomics, Molecular Biology and Biochemistry, Systems Biology
View Dr. Caplen's PubMed Summary.

Selected Recent Publications

  1. Grohar PJ, Kim S, Rangel Rivera GO, Sen N, Haddock S, Harlow ML, Maloney NK, Zhu J, O'Neill M, Jones TL, Huppi K, Grandin M, Gehlhaus K, Klumpp-Thomas CA, Buehler E, Helman LJ, Martin SE, Caplen NJ.
    Cell Reports. 14: 598-610, 2016. [ Journal Article ]
  2. Garimella SV, Gehlhaus K, Dine JL, Pitt JJ, Grandin M, Chakka S, Nau MM, Caplen NJ, Lipkowitz S.
    Breast Cancer Research. 16: R41, 2014. [ Journal Article ]
  3. Ou O, Huppi K, Chakka S, Gehlhaus K, Dubois W, Patel J, Chen J, Mackiewicz M, Jones TL, Pitt JJ, Martin SE, Goldsmith P, Simmons JK, Mock BA, Caplen NJ.
    Cancer Letters. 354: 336-47, 2014. [ Journal Article ]
  4. Caplen NJ, Parrish S, Imani F, Fire A, Morgan RA.
    Proc. Natl. Acad. Sci. U. S. A.. 98: 9742-7, 2001. [ Journal Article ]
  5. Caplen N.J., Alton E. W.F.W., Middleton P.G., Dorin J.R., Stevenson B.J., Gao X., Durham S., Jeffery P.K., Hodson M.E., Coutelle C. Huang L. Porteous D., Williamson R., Geddes D.M.
    Nature Medicine. 1: 39-46, 1995. [ Journal Article ]

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.

Name Position
Allison M. Cross Ph.D. Postdoctoral Fellow (CRTA)
Kwame Donkor Postbaccalaureate Fellow (CRTA)
Tamara L. Jones M.S. Research Biologist
Carla Neckles Ph.D. Postdoctoral Fellow (CRTA)