Bio

Professional Education


  • Doctor of Philosophy, Stanford University, GENE-PHD (2017)
  • Bachelor of Science, Brown University, Biology; Neuroscience (2008)

Publications

All Publications


  • Reversibility of Defective Hematopoiesis Caused by Telomere Shortening in Telomerase Knockout Mice PLOS ONE Raval, A., Behbehani, G. K., Le Xuan Truong Nguyen, L. X., Thomas, D., Kusler, B., Garbuzov, A., Ramunas, J., Holbrook, C., Park, C. Y., Blau, H., Nolan, G. P., Artandi, S. E., Mitchell, B. S. 2015; 10 (7)
  • Reversibility of Defective Hematopoiesis Caused by Telomere Shortening in Telomerase Knockout Mice. PloS one Raval, A., Behbehani, G. K., Nguyen, L. X., Thomas, D., Kusler, B., Garbuzov, A., Ramunas, J., Holbrook, C., Park, C. Y., Blau, H., Nolan, G. P., Artandi, S. E., Mitchell, B. S. 2015; 10 (7)

    Abstract

    Telomere shortening is common in bone marrow failure syndromes such as dyskeratosis congenita (DC), aplastic anemia (AA) and myelodysplastic syndromes (MDS). However, improved knowledge of the lineage-specific consequences of telomere erosion and restoration of telomere length in hematopoietic progenitors is required to advance therapeutic approaches. We have employed a reversible murine model of telomerase deficiency to compare the dependence of erythroid and myeloid lineage differentiation on telomerase activity. Fifth generation Tert-/- (G5 Tert-/-) mice with shortened telomeres have significant anemia, decreased erythroblasts and reduced hematopoietic stem cell (HSC) populations associated with neutrophilia and increased myelopoiesis. Intracellular multiparameter analysis by mass cytometry showed significantly reduced cell proliferation and increased sensitivity to activation of DNA damage checkpoints in erythroid progenitors and in erythroid-biased CD150hi HSC, but not in myeloid progenitors. Strikingly, Cre-inducible reactivation of telomerase activity restored hematopoietic stem and progenitor cell (HSPC) proliferation, normalized the DNA damage response, and improved red cell production and hemoglobin levels. These data establish a direct link between the loss of TERT activity, telomere shortening and defective erythropoiesis and suggest that novel strategies to restore telomerase function may have an important role in the treatment of the resulting anemia.

    View details for DOI 10.1371/journal.pone.0131722

    View details for PubMedID 26133370

    View details for PubMedCentralID PMC4489842

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