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

Anna M. Krichevsky, PhD

Brigham And Women's Hospital


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


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 from Harvard Catalyst Profiles

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  • Zhang Y, Yue C, Krichevsky AM, Garkavtsev I. Repression of the stress granule protein G3BP2 inhibits immune checkpoint molecule PD-L1. Mol Oncol 2021. PubMed
  • Zeng A, Wei Z, Rabinovsky R, Jun HJ, El Fatimy R, Deforzh E, Arora R, Yao Y, Yao S, Yan W, Uhlmann EJ, Charest A, You Y, Krichevsky AM. Glioblastoma-Derived Extracellular Vesicles Facilitate Transformation of Astrocytes via Reprogramming Oncogenic Metabolism. iScience 2020; 23:101420. PubMed
  • Gevaert O, Nabian M, Bakr S, Everaert C, Shinde J, Manukyan A, Liefeld T, Tabor T, Xu J, Lupberger J, Haas BJ, Baumert TF, Hernaez M, Reich M, Quintana FJ, Uhlmann EJ, Krichevsky AM, Mesirov JP, Carey V, Pochet N. Imaging-AMARETTO: An Imaging Genomics Software Tool to Interrogate Multiomics Networks for Relevance to Radiography and Histopathology Imaging Biomarkers of Clinical Outcomes. JCO Clin Cancer Inform 2020; 4:421-435. PubMed
  • Lucero R, Zappulli V, Sammarco A, Murillo OD, Cheah PS, Srinivasan S, Tai E, Ting DT, Wei Z, Roth ME, Laurent LC, Krichevsky AM, Breakefield XO, Milosavljevic A. Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells. Cell Rep 2020; 30:2065-2074.e4. PubMed
  • Abels ER, Maas SLN, Nieland L, Wei Z, Cheah PS, Tai E, Kolsteeg CJ, Dusoswa SA, Ting DT, Hickman S, El Khoury J, Krichevsky AM, Broekman MLD, Breakefield XO. Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21. Cell Rep 2019; 28:3105-3119.e7. PubMed
  • Gyuris A, Navarrete-Perea J, Jo A, Cristea S, Zhou S, Fraser K, Wei Z, Krichevsky AM, Weissleder R, Lee H, Gygi SP, Charest A. Physical and Molecular Landscapes of Mouse Glioma Extracellular Vesicles Define Heterogeneity. Cell Rep 2019; 27:3972-3987.e6. PubMed
  • Krichevsky AM, Uhlmann EJ. Oligonucleotide Therapeutics as a New Class of Drugs for Malignant Brain Tumors: Targeting mRNAs, Regulatory RNAs, Mutations, Combinations, and Beyond. 2019. PubMed
  • Wei Z, Kale S, El Fatimy R, Rabinovsky R, Krichevsky AM. Co-cultures of Glioma Stem Cells and Primary Neurons, Astrocytes, Microglia, and Endothelial Cells for Investigation of Intercellular Communication in the Brain. Front Neurosci 2019; 13:361. PubMed
  • Broekman ML, Maas SLN, Abels ER, Mempel TR, Krichevsky AM, Breakefield XO. Multidimensional communication in the microenvirons of glioblastoma. Nat Rev Neurol 2018; 14:482-495. PubMed
  • Wei Z, Batagov AO, Schinelli S, Wang J, Wang Y, El Fatimy R, Rabinovsky R, Balaj L, Chen CC, Hochberg F, Carter B, Breakefield XO, Krichevsky AM. Coding and noncoding landscape of extracellular RNA released by human glioma stem cells. Nat Commun 2017; 8:1145. PubMed
  • 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 2015; 23:1234-1247. PubMed