Olga Aprelikova, Ph.D.
Olga  Aprelikova, Ph.D.
Staff Scientist

Currently, Dr. Aprelikova studies chromosomal and molecular aberrations selected by tumors driven by well-defined oncogenes, with a focus on Myc-induced mammary carcinomas. The major focus of this study is Myc cooperation with epigenetic modifiers of histone and non-histone proteins involved in transformation of primary epithelial cell and established tumors.

Dr. Aprelikova’s other area of interest focuses on changes in the tumor microenvironment that stimulate primary tumor progression and/or distant metastasis. She identified several microRNAs that are deregulated in cancer-associated fibroblasts and ascertained the effect of those microRNAs and their target genes on tumor growth and motility.

Areas of Expertise
1) tumor microenvironment, 2) hypoxia, 3) microRNA, 4) breast cancer, 5) Myc oncogene

Contact Info

Olga Aprelikova, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 37, Room 1042
Bethesda, MD 20892
301-435-5774
apreliko@mail.nih.gov

Dr. Aprelikova currently performs analysis of genes collaborating with known oncogenes during malignant transformation. Oncogene overexpression in primary cells usually triggers an induction of safeguard  factors to promote cell senescence or apoptosis. Therefore, oncogene-induced tumorigenesis requires cooperating genetic events to overcome these biologic obstacles. 

In order to address this on a genomic scale, we performed a comparative genomic hybridization (CGH) array on 8 genetically engineered mouse (GEM) models of mammary cancer. The MMTV-Myc model displayed a paucity of copy-number variations (CNVs) except for the amplification of the distal region of mouse chromosome 11 in 60% of the tumors.  This region is syntenic with the human chromosome 17q23-25 that is often amplified in human breast cancer.  We hypothesized that some of the 243 gene(s) within this amplicon would cooperate with Myc to enhance tumorigenesis, especially since Myc can exert anti-tumorigenic effects through its ability to induce apoptosis. Analysis of 7 candidate genes that were selected based upon their high expression in Myc-driven tumors have identified JMJD6 as a gene that cooperates with Myc to enhance tumorigenesis.  This gene has pleotropic functions in histone and non-histone protein modifications through catalyzing lysine hydroxylation and, therefore, is capable of regulating gene expression and protein activity.

Recently, JMJD6 was identified as a driver and a marker for poor prognosis in breast cancer, although its mechanism of action was not understood.  We also showed that in already established Myc-driven tumors that are not metastatic, JMJD6 increases their tumor burden, promotes tumor metastasis and induces multiple epithelial-mesenchymal transition (EMT) markers (Twist and Snail) as well as several anti-apototic genes from the Bcl2 family. Given the pleotropic pro-tumorigenic activities of JMJD6 it may be used as a prognostic factor and a therapeutic target for Myc-driven mammary gland tumors.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Chromosome Biology
Selected Recent Publications
  1. Chu IM, Lai WC, Aprelikova O, El Touny LH, Kouros-Mehr H, and Green JE.
    PLoS One. 8(4): e61125, 2013. [ Journal Article ]
  2. Aprelikova O, Palla J, Hibler B, Yu X, Greer YE, Yi M, Stephens R, Maxwell GL, Jazaeri A, Risinger JI, Rubin JS, Niederhuber J.
    Oncogene. 32: 3246-53, 2013. [ Journal Article ]
  3. Aprelikova O, Green JE.
    Cancer Immunol. Immunother. 61: 231-7, 2012. [ Journal Article ]
  4. Aprelikova O, Yu X, Palla J, Wei BR, John S, Yi M, Stephens R, Simpson RM, Risinger JI, Jazaeri A, Niederhuber J.
    Cell Cycle. 9: 4387-98, 2010. [ Journal Article ]
  5. Aprelikova O, Pandolfi S, Tackett S, Ferreira M, Salnikow K, Ward Y, Risinger JI, Barrett JC, Niederhuber J.
    Cancer Res. 69: 616-24, 2009. [ Journal Article ]

Dr. Aprelikova received both her bachelor and master's degrees in biochemistry from Moscow University and her Ph.D. from the Institute of Cytology in St. Petersburg, Russia. She continued her postdoctoral training at the Friedrich Miescher Institute in Basel, Switzerland, in the laboratory of Dr. Joseph Jiricny, where she focused on the repair of spontaneous DNA lesions, and then at the University of Helsinki (Helskinki, Finland), in the laboratory of Dr. Kari Alitalo, where she identified, cloned and characterized the novel VEGF receptor, FLT4. In 1993 she joined the laboratory of Dr. Edison Liu at the University of North Carolina at Chapel Hill, where she studied the biological function of BRCA1. She started working at the NCI in 1997 where she continued her research in breast cancer, and later, in tumor hypoxia.

Research

Dr. Aprelikova currently performs analysis of genes collaborating with known oncogenes during malignant transformation. Oncogene overexpression in primary cells usually triggers an induction of safeguard  factors to promote cell senescence or apoptosis. Therefore, oncogene-induced tumorigenesis requires cooperating genetic events to overcome these biologic obstacles. 

In order to address this on a genomic scale, we performed a comparative genomic hybridization (CGH) array on 8 genetically engineered mouse (GEM) models of mammary cancer. The MMTV-Myc model displayed a paucity of copy-number variations (CNVs) except for the amplification of the distal region of mouse chromosome 11 in 60% of the tumors.  This region is syntenic with the human chromosome 17q23-25 that is often amplified in human breast cancer.  We hypothesized that some of the 243 gene(s) within this amplicon would cooperate with Myc to enhance tumorigenesis, especially since Myc can exert anti-tumorigenic effects through its ability to induce apoptosis. Analysis of 7 candidate genes that were selected based upon their high expression in Myc-driven tumors have identified JMJD6 as a gene that cooperates with Myc to enhance tumorigenesis.  This gene has pleotropic functions in histone and non-histone protein modifications through catalyzing lysine hydroxylation and, therefore, is capable of regulating gene expression and protein activity.

Recently, JMJD6 was identified as a driver and a marker for poor prognosis in breast cancer, although its mechanism of action was not understood.  We also showed that in already established Myc-driven tumors that are not metastatic, JMJD6 increases their tumor burden, promotes tumor metastasis and induces multiple epithelial-mesenchymal transition (EMT) markers (Twist and Snail) as well as several anti-apototic genes from the Bcl2 family. Given the pleotropic pro-tumorigenic activities of JMJD6 it may be used as a prognostic factor and a therapeutic target for Myc-driven mammary gland tumors.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Chromosome Biology

Publications

Selected Recent Publications
  1. Chu IM, Lai WC, Aprelikova O, El Touny LH, Kouros-Mehr H, and Green JE.
    PLoS One. 8(4): e61125, 2013. [ Journal Article ]
  2. Aprelikova O, Palla J, Hibler B, Yu X, Greer YE, Yi M, Stephens R, Maxwell GL, Jazaeri A, Risinger JI, Rubin JS, Niederhuber J.
    Oncogene. 32: 3246-53, 2013. [ Journal Article ]
  3. Aprelikova O, Green JE.
    Cancer Immunol. Immunother. 61: 231-7, 2012. [ Journal Article ]
  4. Aprelikova O, Yu X, Palla J, Wei BR, John S, Yi M, Stephens R, Simpson RM, Risinger JI, Jazaeri A, Niederhuber J.
    Cell Cycle. 9: 4387-98, 2010. [ Journal Article ]
  5. Aprelikova O, Pandolfi S, Tackett S, Ferreira M, Salnikow K, Ward Y, Risinger JI, Barrett JC, Niederhuber J.
    Cancer Res. 69: 616-24, 2009. [ Journal Article ]

Biography

Dr. Aprelikova received both her bachelor and master's degrees in biochemistry from Moscow University and her Ph.D. from the Institute of Cytology in St. Petersburg, Russia. She continued her postdoctoral training at the Friedrich Miescher Institute in Basel, Switzerland, in the laboratory of Dr. Joseph Jiricny, where she focused on the repair of spontaneous DNA lesions, and then at the University of Helsinki (Helskinki, Finland), in the laboratory of Dr. Kari Alitalo, where she identified, cloned and characterized the novel VEGF receptor, FLT4. In 1993 she joined the laboratory of Dr. Edison Liu at the University of North Carolina at Chapel Hill, where she studied the biological function of BRCA1. She started working at the NCI in 1997 where she continued her research in breast cancer, and later, in tumor hypoxia.