Photo of Zuzana Tothova,  MD, PhD

Zuzana Tothova, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute


zuzana_tothova@dfci.harvard.edu

Zuzana Tothova, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Instructor, Medicine, Harvard Medical School
  • Instructor, Medical Oncology, Dana-Farber Cancer Institute
  • Instructor, Medicine, Brigham And Women's Hospital
  • Associate Member, Cancer Program, Broad Institute of MIT and Harvard

DF/HCC PROGRAM AFFILIATION

Research Abstract

The primary focus of the Tothova laboratory is investigation of the biology, genetics and treatment of myeloid malignancies, including the premalignant state of clonal hematopoiesis (CHIP), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our goal is to contribute to our understanding of the effect of chromatin organization on hematopoietic stem cell (HSC) transformation in the context of mutations in cohesin genes and other epigenetic modulators recurrently mutated in myeloid malignancies. We employ a combination of genomic, genome engineering, mouse modeling as well as classical biochemistry, cellular and molecular biology approaches to answer disease-relevant questions with the goal to identify novel therapeutic targets that can be translated to true patient benefit in the future.

Publications

Powered by Harvard Catalyst
  • Tothova Z, Krill-Burger JM, Popova KD, Landers CC, Sievers QL, Yudovich D, Belizaire R, Aster JC, Morgan EA, Tsherniak A, Ebert BL. Multiplex CRISPR/Cas9-Based Genome Editing in Human Hematopoietic Stem Cells Models Clonal Hematopoiesis and Myeloid Neoplasia. Cell Stem Cell 2017; 21:547-555.e8. PubMed
  • Tothova Z, Ebert BL. Doubling Down on Mutant RAS Can MEK or Break Leukemia. Cell 2017; 168:749-750. PubMed
  • Puram RV, Kowalczyk MS, de Boer CG, Schneider RK, Miller PG, McConkey M, Tothova Z, Tejero H, Heckl D, Järås M, Chen MC, Li H, Tamayo A, Cowley GS, Rozenblatt-Rosen O, Al-Shahrour F, Regev A, Ebert BL. Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML. Cell 2016; 165:303-16. PubMed
  • Elf S, Abdelfattah NS, Chen E, Perales-Paton J, Rosen EA, Ko A, Peisker F, Florescu N, Giannini S, Wolach O, Morgan EA, Tothova Z, Losman JA, Schneider RK, Al-Shahrour F, Mullally A. Mutant calreticulin requires both its mutant C-terminus and the thrombopoietin receptor for oncogenic transformation. 2016. PubMed
  • Doench JG, Fusi N, Sullender M, Hegde M, Vaimberg EW, Donovan KF, Smith I, Tothova Z, Wilen C, Orchard R, Virgin HW, Listgarten J, Root DE. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat Biotechnol 2017; 34:184-191. PubMed
  • Doench JG, Hartenian E, Graham DB, Tothova Z, Hegde M, Smith I, Sullender M, Ebert BL, Xavier RJ, Root DE. Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation. Nat Biotechnol 2014. PubMed
  • Tothova Z, Berliner N. Hemophagocytic Syndrome and Critical Illness: New Insights into Diagnosis and Management. J Intensive Care Med 2014. PubMed
  • Hartwell KA, Miller PG, Mukherjee S, Kahn AR, Stewart AL, Logan DJ, Negri JM, Duvet M, Järås M, Puram R, Dancik V, Al-Shahrour F, Kindler T, Tothova Z, Chattopadhyay S, Hasaka T, Narayan R, Dai M, Huang C, Shterental S, Chu LP, Haydu JE, Shieh JH, Steensma DP, Munoz B, Bittker JA, Shamji AF, Clemons PA, Tolliday NJ, Carpenter AE, Gilliland DG, Stern AM, Moore MA, Scadden DT, Schreiber SL, Ebert BL, Golub TR. Niche-based screening identifies small-molecule inhibitors of leukemia stem cells. Nat Chem Biol 2013; 9:840-8. PubMed
  • Tothova Z, Steensma DP, Ebert BL. New strategies in myelodysplastic syndromes: application of molecular diagnostics to clinical practice. Clin Cancer Res 2013; 19:1637-43. PubMed
  • Tothova Z, Wagner AJ. Anaplastic lymphoma kinase-directed therapy in inflammatory myofibroblastic tumors. Curr Opin Oncol 2012; 24:409-13. PubMed
  • Sykes SM, Lane SW, Bullinger L, Kalaitzidis D, Yusuf R, Saez B, Ferraro F, Mercier F, Singh H, Brumme KM, Acharya SS, Scholl C, Schöll C, Tothova Z, Attar EC, Fröhling S, DePinho RA, Armstrong SA, Gilliland DG, Scadden DT. AKT/FOXO signaling enforces reversible differentiation blockade in myeloid leukemias. Cell 2011; 146:697-708. PubMed
  • Cornejo MG, Mabialah V, Sykes SM, Khandan T, Lo Celso C, Lopez CK, Rivera-Muñoz P, Rameau P, Tothova Z, Aster JC, DePinho RA, Scadden DT, Gilliland DG, Mercher T. Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification. Blood 2011; 118:1264-73. PubMed
  • Lee JY, Nakada D, Yilmaz OH, Tothova Z, Joseph NM, Lim MS, Gilliland DG, Morrison SJ. mTOR activation induces tumor suppressors that inhibit leukemogenesis and deplete hematopoietic stem cells after Pten deletion. Cell Stem Cell 2017; 7:593-605. PubMed
  • Tothova Z, Gilliland DG. A radical bailout strategy for cancer stem cells. Cell Stem Cell 2009; 4:196-7. PubMed
  • Lee BH, Tothova Z, Levine RL, Anderson K, Buza-Vidas N, Cullen DE, McDowell EP, Adelsperger J, Fröhling S, Huntly BJ, Beran M, Jacobsen SE, Gilliland DG. FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia. Cancer Cell 2018; 12:367-80. PubMed
  • Tothova Z, Gilliland DG. FoxO transcription factors and stem cell homeostasis: insights from the hematopoietic system. Cell Stem Cell 2008; 1:140-52. PubMed
  • Tothova Z, Mercher T. [FoxO: stress or eternal life]. Med Sci (Paris) 2016; 23:466-7. PubMed
  • Klose RJ, Yan Q, Tothova Z, Yamane K, Erdjument-Bromage H, Tempst P, Gilliland DG, Zhang Y, Kaelin WG. The retinoblastoma binding protein RBP2 is an H3K4 demethylase. Cell 2007; 128:889-900. PubMed
  • Paik JH, Kollipara R, Chu G, Ji H, Xiao Y, Ding Z, Miao L, Tothova Z, Horner JW, Carrasco DR, Jiang S, Gilliland DG, Chin L, Wong WH, Castrillon DH, DePinho RA. FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell 2007; 128:309-23. PubMed
  • Tothova Z, Kollipara R, Huntly BJ, Lee BH, Castrillon DH, Cullen DE, McDowell EP, Lazo-Kallanian S, Williams IR, Sears C, Armstrong SA, Passegu. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 2007; 128:325-39. PubMed
  • Masutomi K, Possemato R, Wong JM, Currier JL, Tothova Z, Manola JB, Ganesan S, Lansdorp PM, Collins K, Hahn WC. The telomerase reverse transcriptase regulates chromatin state and DNA damage responses. Proc Natl Acad Sci U S A 2005; 102:8222-7. PubMed
  • Gu TL, Tothova Z, Scheijen B, Griffin JD, Gilliland DG, Sternberg DW. The NPM-ALK Fusion Kinase of Anaplastic Large Cell Lymphoma Regulates Survival and Proliferative Signaling Through Modulation of FOXO3a. Blood 2004; 103:4622-9. PubMed
Hide