Anna A Friedl

Anna A Friedl
Ludwig-Maximilians-University of Munich | LMU · Department of Radiation Oncology

Dr

About

160
Publications
13,267
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2,696
Citations
Citations since 2016
62 Research Items
1285 Citations
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
Introduction
Additional affiliations
September 2009 - present
Ludwig-Maximilians-University of Munich
Position
  • Group Leader

Publications

Publications (160)
Article
Radiation exposures at ultra‐high dose rates (UHDR) at several orders of magnitude greater than in current clinical radiotherapy have been shown to manifest differential radiobiological responses compared to conventional dose rates (CONV). This has led to studies investigating the application of UHDR for therapeutic advantage (FLASH‐RT) which have...
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Background Invasiveness is a major factor contributing to metastasis of tumour cells. Given the broad variety and plasticity of invasion mechanisms, assessing potential metastasis-promoting effects of irradiation for specific mechanisms is important for further understanding of potential adverse effects of radiotherapy. In fibroblast-led invasion m...
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Background: Charged-particle radiotherapy is an emerging treatment modality for radioresistant tumors. The enhanced effectiveness of high-energy particles (such as heavy ions) has been related to the spatial clustering of DNA lesions due to highly localized energy deposition. Here, DNA damage patterns induced by single and multiple carbon ions wer...
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Radiotherapy is an essential component of multi-modality treatment of glioblastoma(GBM). However, treatment failure and recurrence are frequent and give rise to the dismal prognosis of this aggressive type of primary brain tumor. A high level of inherent treatment resistance is considered to be the major underlying reason, stemming from constantly...
Article
The development from single shot basic laser plasma interaction research toward experiments in which repetition rated laser-driven ion sources can be applied requires technological improvements. For example, in the case of radio-biological experiments, irradiation duration and reproducible controlled conditions are important for performing studies...
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This paper summarises the view of the German Commission on Radiological Protection (“Strahlenschutzkommission”, SSK) on the rationale behind the currently valid dose limits and dose constraints for workers recommended by the International Commission on Radiological Protection (ICRP). The paper includes a discussion of the reasoning behind current d...
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Purpose: Humans are increasingly exposed to ionising radiation (IR). Both low (<100 mGy) and high doses can cause stochastic effects, including cancer; whereas doses above 100 mGy are needed to promote tissue or cell damage. 10-15% of radiotherapy (RT) patients suffer adverse reactions, described as displaying radiosensitivity (RS). Sensitivity to...
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Nucleoli gained interest for their role as cellular stress sensors and as potential targets for cancer treatment. The effect of DNA double-strand breaks (DSBs) in nucleoli on rRNA transcription or nucleolar organisation appears to depend on the agent used to introduce DSBs, DSB frequency and presence (or not) of DSBs outside the nucleoli. We target...
Article
The accumulation and spatial distribution of 53BP1, BRCA1 and Rad51, key proteins in DNA double-strand break (DSB) repair, was investigated with high temporal resolution over a time span of 24 h, using STED nanoscopy. DNA lesions were induced by irradiation with high-LET (linear energy transfer) α-particles. We show that 53BP1 IRIF formation occurs...
Article
Purpose: The review aims to discuss the prominence of dietary and metabolic regulators in maintaining HSC function, long-term self-renewal and differentiation. Results: Most adult stem cells are preserved in a quiescent, non-motile state in vivo which acts as a “protective state” for stem cells to reduce endogenous stress provoked by DNA replicatio...
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The spatial distribution of DSB repair factors γH2AX, 53BP1 and Rad51 in ionizing radiation induced foci (IRIF) in HeLa cells using super resolution STED nanoscopy after low and high linear energy transfer (LET) irradiation was investigated. 53BP1 and γH2AX form IRIF with same mean size of (540 ± 40) nm after high LET irradiation while the size aft...
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Histone demethylases have recently gained interest as potential targets in cancer treatment and several histone demethylases have been implicated in the DNA damage response. We investigated the effects of siRNA-mediated depletion of histone demethylase Jarid1A (KDM5A, RBP2), which demethylates transcription activating tri- and dimethylated lysine 4...
Data
Depletion of Jarid1A does not lead to strong induction of p21. Expression of p21 after depletion of Jarid1A in HeLa, MCF-7 and U2OS cells, 72 h after transfection with scr or Jarid1A siRNA. A representative sample and its quantitative evaluation are shown. Cont = untransfected control. (TIF)
Data
Depletion of Jarid1A does not affect anti-correlation of γH2AX and H3K4me3 or active RNA Pol II, respectively, after ion irradiation. HeLa cell transfected with scr or Jarid1A A1+A3 siRNAs were subject to ion microirradiation with single carbon ions applied in line patterns (lateral distance between single ion hits 1 μm, distance between “lines” 5...
Data
Early formation of γH2AX foci is not affected by depletion of Jarid1A. 72 h after transfection with scr or Jarid1A A1+A3 siRNA, HeLa cells were irradiated in a small angle configuration with 55 MeV carbon ions and fixed after 5 min (A) and 2 min (B), or irradiated with 5 Gy X-rays and fixed after 15 min (C). Indirect immunofluorescence was performe...
Data
Depletion of Jarid1A enhances radiosensitivity. Colony formation experiment with Hela cells transfected with JaridA1 siRNAs A1 or A3 or a combination thereof, as well as untransfected controls and cells transfected with scr siRNA. Cells were irradiated 72 h after siRNA transfection with 0 Gy, 2 Gy, 5 Gy or 10 Gy X-rays. Cells were incubated for 10...
Data
Background and residual 53BP1 and Rad51 foci are not affected by depletion of Jarid1A. Mean background frequency and number of residual 53BP1 and Rad51 foci (+/- SEM) were determined in at least 20 cells after 5 Gy X-irradiation. Cells were fixed before irradiation or at 24 h and 48 h after irradiation and indirect immunofluorescence was performed....
Data
Efficient down-regulation of Jarid1A is associated with a global increase of H3K4me3. (A) Decreased levels of Jarid1A in whole cell protein extracts of HeLa, MCF-7 and U2OS cells after siRNA transfection. Western blot images show levels of Jarid1A in untransfected cells (cont), in cells transfected with scrambled siRNA (scr) and in cells transfecte...
Data
MNase accessibility is not affected by Jarid1A depletion. Analysis of chromatin accessibility by MNase digestion of isolated nuclei. After different incubation periods with 0.5 u MNase, comparable amounts of partially digested DNA were loaded onto an agarose gel. The emerging ladder of mono- and oligonucleosomes is comparable in both samples indica...
Data
Comparison of relative band intensities corresponding to Jarid1A and Jarid1B proteins. Band intensities were normalized with respect to Tubulin loading control. Intensities in HeLa cells were set as 100%. All bands to be compared were on the same blot. Data are from 2 Western Blots. (DOCX)
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The chaperone heat shock protein 90 (HSP90) crucially supports the maturation, folding, and stability of a variety of client proteins which are of pivotal importance for the survival and proliferation of cancer cells. Consequently, targeting of HSP90 has emerged as an attractive strategy of anti-cancer therapy, and it appears to be particularly eff...
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Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and...
Data
PARP1 chromobody expression in living cells does not significantly affect cell viability or PARP1 enzymatic activity. (A) Comparison of the metabolic viability of HeLa cells transiently expressing PARP1 chromobody and untransfected HeLa cells (nt) in resazurin assay (alamarBlue). Percentages of viable cells after 24 h of proliferation were determin...
Data
Recruitment of GFP-hPARP1 and PARP1 chromobody to the DNA damage sites induced by laser microirradiation. HeLa cells transiently co-transfected with GFP-hPARP1 and PARP1 chromobody (TagRFP) were subjected to confocal imaging upon microirradiation with a 405 nm diode laser for 1 second. Time-lapse imaging was carried out at 1 frame per second rate w...
Data
Monitoring of laser-induced DNA damage with PARP1 chromobody in human and non-human cells. (A) Live-cell imaging of laser-microirradiated (405 nm laser, 100% power, 1 s) cells transiently expressing the PARP1 chromobody. Time-lapse imaging was carried out at 1 frame per second rate with a spinning disc microscope acquiring 9 pre-irradiation and 100...
Data
Live-cell movie of HeLa cells expressing PARP1 chromobody treated with 10 μM camptothecin followed by recovery. (GIF)
Data
Live-cell movie of laser-irradiated HeLa cells transiently expressing PARP1 chromobody. (GIF)
Data
Amino acid substitutions within the human PARP1 ZnF2 domain significantly decrease binding of the PARP1 nanotrap. (A) Amino-acid sequence alignment of the PARP1 ZnF2 domains from hamster (Mesocricetus auratus, NCBI Reference Sequence: XP_005078195.1), mouse (Mus musculus, NCBI Reference Sequence: NP_031441.2) and human (Homo sapiens, NCBI Reference...
Data
On-bead pADPr chain synthesis with immunoprecipitated endogenous hPARP1 after pull-down with the PARP1 nanotrap. Absorbance spectra of synthesized and purified pADPr polymers are shown. Reaction with the purified recombinant hPARP1 with NAD+ (A) or without NAD+ (B); on-bead reaction with PARP1 nanotrap-precipitated endogenous hPARP1 with NAD+ (C) o...
Data
High content analysis of compound potencies to delocalize hPARP1 from nucleoli as determined based on the PARP1 chromobody signal. HeLa cells stably expressing PARP1 chromobody were treated with different concentrations of 4-NQO, actinomycin D, camptothecin and H2O2 (titration series from 0.01 μM up to 1 mM) for 4 h. Subsequently, cells were fixed...
Data
Live-cell movie of carbon ion-irradiated HeLa cells transiently expressing PARP1 chromobody. (GIF)
Article
Full-text available
There is a need to develop new, more efficient therapies for head and neck cancer (HNSCC) patients. It is currently unclear whether defects in DNA repair genes play a role in HNSCCs' resistance to therapy. PARP1 inhibitors (PARPi) were found to be "synthetic lethal" in cancers deficient in BRCA1/2 with impaired homologous recombination. Since tumor...
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Many proteins involved in detection, signalling and repair of DNA double-strand breaks (DSB) accumulate in large number in the vicinity of DSB sites, forming so called foci. Emerging evidence suggests that these foci are sub-divided in structural or functional domains. We use stimulated emission depletion (STED) microscopy to investigate localizati...
Data
Agreement of quantitative determination of G2/M phase cells by FACS analysis and microscopy. This figure shows the results of a quantitative evaluation of the number of G2/M phase cells determined by FACS analysis and microscopy in parallel samples.
Data
Microscopic identification of apoptotic cells. This figure shows examples of apoptotic cells identified by staining for cleaved caspase 3 and by appearance after DAPI staining.
Data
Dose-dependence of accumulation of cells in G2 phase after x-irradiation. This figure shows the frequency of cells in G2 phase after irradiation with 0, 3 and 5 Gy and incubation for 0, 10, 24 and 48 h.
Article
Full-text available
Ion microbeams are important tools in radiobiological research. Still, the worldwide number of ion microbeam facilities where biological experiments can be performed is limited. Even fewer facilities combine ion microirradiation with live-cell imaging to allow microscopic observation of cellular response reactions starting very fast after irradiati...