Judith Staerk

• Papadopoulos, Nicolas; Pristavec, Ajda; Nédélec, Audrey; Levy, Gabriel; Staerk, Judith & Constantinescu, Stefan N. (2023). Modulation of human thrombopoietin receptor conformations uncouples JAK2 V617F-driven activation from cytokine-induced stimulation. Blood. ISSN 0006-4971. doi: 10.1182/blood.2022019580. Full text in Research Archive
• Reint, Ganna; Li, Zhuokun; Labun, Kornel; Keskitalo, Salla; Soppa, Inkeri & Mamia, Katariina Aino Inkeri [Show all 19 contributors for this article] (2021). Rapid genome editing by CRISPR-Cas9-POLD3 fusion. eLIFE. ISSN 2050-084X. 11. doi: 10.7554/eLife.75415. Full text in Research Archive Show summary

  Precision CRISPR gene editing relies on the cellular homology-directed DNA repair (HDR) to introduce custom DNA sequences to target sites. The HDR editing efficiency varies between cell types and genomic sites, and the sources of this variation are incompletely understood. Here, we have studied the effect of 450 DNA repair protein - Cas9 fusions on CRISPR genome editing outcomes. We find the majority of fusions to improve precision genome editing only modestly in a locus- and cell-type specific manner. We identify Cas9-POLD3 fusion that enhances editing by speeding up the initiation of DNA repair. We conclude that while DNA repair protein fusions to Cas9 can improve HDR CRISPR editing, most need to be optimized to the cell type and genomic site, highlighting the diversity of factors contributing to locus-specific genome editing outcomes.

• Caglayan, Safak; Hashim, Adnan; Cieslar-Pobuda, Artur; Jensen, Vidar; Behringer, Sidney & Talug, Burcu [Show all 16 contributors for this article] (2020). Optic Atrophy 1 Controls Human Neuronal Development by Preventing Aberrant Nuclear DNA Methylation. iScience. ISSN 2589-0042. 23(6). doi: 10.1016/j.isci.2020.101154. Full text in Research Archive Show summary

  Optic atrophy 1 (OPA1), a GTPase at the inner mitochondrial membrane involved in regulating mitochondrial fusion, stability, and energy output, is known to be crucial for neural development: Opa1 heterozygous mice show abnormal brain development, and inactivating mutations in OPA1 are linked to human neurological disorders. Here, we used genetically modified human embryonic and patient-derived induced pluripotent stem cells and reveal that OPA1 haploinsufficiency leads to aberrant nuclear DNA methylation and significantly alters the transcriptional circuitry in neural progenitor cells (NPCs). For instance, expression of the forkhead box G1 transcription factor, which is needed for GABAergic neuronal development, is repressed in OPA1+/− NPCs. Supporting this finding, OPA1+/− NPCs cannot give rise to GABAergic interneurons, whereas formation of glutamatergic neurons is not affected. Taken together, our data reveal that OPA1 controls nuclear DNA methylation and expression of key transcription factors needed for proper neural cell specification.

• Cieslar-Pobuda, Artur; Ahrens, Theresa Dorothee; Caglayan, Safak; Behringer, Sidney; Hannibal, Luciana & Staerk, Judith (2020). DNMT3B deficiency alters mitochondrial biogenesis and α‐ketoglutarate levels in human embryonic stem cells. Stem Cells. ISSN 1066-5099. 38(11), p. 1409–1422. doi: 10.1002/stem.3256. Full text in Research Archive Show summary

  Embryonic stem cell renewal and differentiation is regulated by metabolites that serve as cofactors for epigenetic enzymes. An increase of α‐ketoglutarate (α‐KG), a cofactor for histone and DNA demethylases, triggers multilineage differentiation in human embryonic stem cells (hESCs). To gain further insight into how the metabolic fluxes in pluripotent stem cells can be influenced by inactivating mutations in epigenetic enzymes, we generated hESCs deficient for de novo DNA methyltransferases (DNMTs) 3A and 3B. Our data reveal a bidirectional dependence between DNMT3B and α‐KG levels: a‐KG is significantly upregulated in cells deficient for DNMT3B, while DNMT3B expression is downregulated in hESCs treated with α‐KG. In addition, DNMT3B null hESCs exhibit a disturbed mitochondrial fission and fusion balance and a switch from glycolysis to oxidative phosphorylation. Taken together, our data reveal a novel link between DNMT3B and the metabolic flux of hESCs.

• Behringer, Sidney; Wingert, Victoria; Oria, Victor; Schumann, Anke; Grünert, Sarah & Cieslar-Pobuda, Artur [Show all 13 contributors for this article] (2019). Targeted metabolic profiling of methionine cycle metabolites and redox thiol pools in mammalian plasma, cells and urine. Metabolites. ISSN 2218-1989. 9:235(10), p. 1–27. doi: 10.3390/metabo9100235. Full text in Research Archive
• Luhr, Morten; Torgersen, Maria Lyngaas; Szalai, Paula; Hashim, Adnan; Brech, Andreas & Stärk, Judith [Show all 7 contributors for this article] (2019). The kinase PERK and the transcription factor ATF4 play distinct and essential roles in autophagy resulting from tunicamycin-induced ER stress. Journal of Biological Chemistry. ISSN 0021-9258. 294(20), p. 8197–8217. doi: 10.1074/jbc.RA118.002829. Full text in Research Archive
• Rogne, Marie; Svärd, Oksana; Madsen-Østerbye, Julia-Kristina Jensen; Hashim, Adnan; Tjønnfjord, Geir Erland & Staerk, Judith (2018). Cytokinesis arrest and multiple centrosomes in B cell chronic lymphocytic leukaemia. Journal of Cellular and Molecular Medicine. ISSN 1582-1838. 22(5), p. 2846–2855. doi: 10.1111/jcmm.13579. Full text in Research Archive
• Tekpli, Xavier; Urbanucci, Alfonso; Hashim, Adnan; Vågbø, Cathrine Broberg; Lyle, Robert & Kringen, Marianne K. [Show all 11 contributors for this article] (2016). Changes of 5-hydroxymethylcytosine distribution during myeloid and lymphoid differentiation of CD34+ cells. Epigenetics & Chromatin. ISSN 1756-8935. 9. doi: 10.1186/s13072-016-0070-8. Full text in Research Archive
• Leroy, Emilie; Defour, Jean-Philippe; Sato, Takeshi; Dass, Sharmila; Gryshkova, Vitalina & Shwe, Myat [Show all 9 contributors for this article] (2016). His499 Regulates Dimerization and Prevents Oncogenic Activation by Asparagine Mutations of the Human Thrombopoietin Receptor. Journal of Biological Chemistry. ISSN 0021-9258. 291(6), p. 2974–2987. doi: 10.1074/jbc.M115.696534.
• Leroy, Emilie; Defour, JP; Sato, T.; Dass, S; Gryshkova, V & Myat Marlar, S [Show all 9 contributors for this article] (2016). His499 Regulates Dimerization and Prevents Oncogenic Activation by Asparagine Mutations of the Human Thrombopoietin Receptor. Journal of Biological Chemistry. ISSN 0021-9258. 291(6), p. 2974–2987. doi: 10.1074/jbc.M115.696534.

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• Ahrens, Theresa Dorothee; Caglayan, Safak; Staerk, Judith & Cieslar-Pobuda, Artur (2018). Transdifferentiation – changing cell identity. Academic Press. ISBN 9780128122785. 249 p.
• Caglayan, Safak; Ahrens, Theresa Dorothee; Cieslar-Pobuda, Artur & Staerk, Judith (2018). Modern ways of obtaining stem cells. Academic Press. ISBN 9780128122785. 249 p.

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• Reint, Ganna; Li, Zhuokun; Labun, Kornel; Keskitalo, Salla; Soppa, Inkeri & Mamia, Katariina Aino Inkeri [Show all 19 contributors for this article] (2022). Rapid genome editing by CRISPR-Cas9-POLD3 fusion. .

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