Photo of Anna M. Krichevsky,  PhD

Anna M. Krichevsky, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-5195
Fax: (617) 525-5252


akrichevsky@partners.org

Anna M. Krichevsky, PhD

Brigham And Women's Hospital

EDUCATIONAL TITLES

  • Associate Professor, Neurology, Harvard Medical School
  • Scientist, Center for Neurologic Diseases, Neurology, Brigham And Women's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The work in the laboratory focuses on small regulatory RNA molecules, microRNAs, their role in brain tumors, and potential as novel therapeutic targets and biomarkers. We are also interested in the RNA-mediated intracellular communication between brain tumors and normal cells of their microenvironment. Our overall goal is to develop basic RNA research toward a cure for glioblastoma (GBM) and other brain tumors.

We have identified key miRNAs that regulate various signaling pathways underlying glioma progression, including miR-21, miR-296, miR-148a, and miR-10b. As an example, the ongoing work focuses on miR-10b, a unique oncogenic miRNA that is highly expressed in all GBM subtypes, while absent in normal neuroglial cells of the brain. miR-10b inhibition strongly impairs proliferation and survival of cultured glioma cells, including glioma-initiating stem-like cells (GSC). Furthermore, GBM is strictly “addicted” to miR-10b, and miR-10b gene ablation by CRISPR/Cas9 editing system is lethal for glioma cell cultures and established intracranial tumors. miR-10b loss-of-function leads to the death of glioma, but not of other cancer or normal neural cells. Administration of miR-10b antisense oligonucleotide inhibitors (ASO) through direct intratumoral injections, continuous osmotic delivery, and systemic intravenous injections attenuate growth and progression of established intracranial GBM. These results indicate that miR-10b is a strong candidate for the development of targeted therapies against various GBM subtypes. Despite its critical role in gliomagenesis, neither the mechanisms of miR-10b induction nor its signaling is sufficiently investigated, representing an exciting avenue for our ongoing work.

Publications

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  • Yanachkov I, Zavizion B, Metelev V, Stevens LJ, Tabatadze Y, Yanachkova M, Wright G, Krichevsky AM, Tabatadze DR. Self-neutralizing oligonucleotides with enhanced cellular uptake. Org Biomol Chem 2017; 15:1363-1380. PubMed
  • El Fatimy R, Subramanian S, Uhlmann EJ, Krichevsky AM. Genome Editing Reveals Glioblastoma Addiction to MicroRNA-10b. Mol Ther 2017; 25:368-378. PubMed
  • Wei Z, Batagov AO, Carter DR, Krichevsky AM. Fetal Bovine Serum RNA Interferes with the Cell Culture derived Extracellular RNA. Sci Rep 2016; 6:31175. PubMed
  • Teplyuk NM, Uhlmann EJ, Gabriely G, Volfovsky N, Wang Y, Teng J, Karmali P, Marcusson E, Peter M, Mohan A, Kraytsberg Y, Cialic R, Chiocca EA, Godlewski J, Tannous B, Krichevsky AM. Therapeutic potential of targeting microRNA-10b in established intracranial glioblastoma: first steps toward the clinic. EMBO Mol Med 2016; 8:268-87. PubMed
  • Wong HA, Fatimy RE, Onodera C, Wei Z, Yi M, Mohan A, Gowrisankaran S, Karmali P, Marcusson E, Wakimoto H, Stephens R, Uhlmann EJ, Song JS, Tannous B, Krichevsky AM. The Cancer Genome Atlas Analysis Predicts MicroRNA for Targeting Cancer Growth and Vascularization in Glioblastoma. Mol Ther 2017; 23:1234-1247. PubMed