A5029670570- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Electrochemical Analysis and Applications
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Trace Elements in Health
- Mass Spectrometry Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- PARP inhibition in cancer therapy
- Gut microbiota and health
- Cancer Research and Treatments
- CRISPR and Genetic Engineering
- Cancer Cells and Metastasis
- Virus-based gene therapy research
University of Bern
2022-2024
Abstract Histone H2AX plays a key role in DNA damage signalling the surrounding regions of double-strand breaks (DSBs). In response to damage, becomes phosphorylated on serine residue 139 (known as γH2AX), resulting recruitment repair effectors 53BP1 and BRCA1. Here, by studying resistance poly(ADP-ribose) polymerase (PARP) inhibitors BRCA1/2-deficient mammary tumours, we identify function for γH2AX orchestrating drug-induced replication fork degradation. Mechanistically, γH2AX-driven...
Breast cancer remains one of the prominent causes death worldwide. Although chemotherapeutic agents often result in substantial reduction primary or metastatic tumours, remaining drug-tolerant tumour cell populations, known as minimal residual disease (MRD), pose a significant risk recurrence and therapy resistance. In this study, we describe spatiotemporal organisation response MRD BRCA1;p53-deficient mouse mammary tumours human clinical samples using multimodal approach. By integrating...
The persistence of drug-sensitive tumors poses a significant challenge in cancer treatment. concept bacterial persisters, which are subpopulation bacteria that survive lethal antibiotic doses, is frequently used to compare residual disease cancer. Here, we explore drug tolerance cells and bacteria. We highlight the fact bacteria, contrast cells, have been selected for survival at population level may therefore possess contingency mechanisms lack. precise drug-tolerant persisters still being...
In recent years, platinum (Pt) drugs have been found to be especially efficient treat patients with cancers that lack a proper DNA damage response, for example, due dysfunctional BRCA1. Despite this knowledge, we are still missing helpful markers predict Pt response in the clinic. We previously shown volume-regulated anion channels, containing subunits LRRC8A and LRRC8D, promote uptake of cisplatin carboplatin BRCA1-proficient cell lines. Here, show loss or LRRC8D significantly reduces...
Abstract Although various effective anti-cancer treatments have become available over the last decades, resistance to all therapies remains major cause of death cancer patients with disseminated tumors. Striking examples are triple-negative breast (TNBC), which frequently defective in repair DNA double strand breaks, e.g. due loss BRCA1 function. Because this defect, initially respond very well damage-inducing chemotherapy. Unfortunately, tumors usually not eradicated and resistant tumor...
<div><p>In recent years, platinum (Pt) drugs have been found to be especially efficient treat patients with cancers that lack a proper DNA damage response, for example, due dysfunctional BRCA1. Despite this knowledge, we are still missing helpful markers predict Pt response in the clinic. We previously shown volume-regulated anion channels, containing subunits LRRC8A and LRRC8D, promote uptake of cisplatin carboplatin BRCA1-proficient cell lines. Here, show loss or LRRC8D...
<div><p>In recent years, platinum (Pt) drugs have been found to be especially efficient treat patients with cancers that lack a proper DNA damage response, for example, due dysfunctional BRCA1. Despite this knowledge, we are still missing helpful markers predict Pt response in the clinic. We previously shown volume-regulated anion channels, containing subunits LRRC8A and LRRC8D, promote uptake of cisplatin carboplatin BRCA1-proficient cell lines. Here, show loss or LRRC8D...
<p>Primer sequences used for Lrrc8a or Lrrc8d knockout control in 2D cell lines mice reconstitution experiments</p>
<p>Generation of monoclonal knockout cell lines Lrrc8a or Lrrc8d used in main Figure</p>
<p>gRNA oligos used for the generation of Lrrc8a or Lrrc8d-knockout cell lines, organoids and tumors</p>
<p>Blasticidin and Pt treatment of Lrrc8a or Lrrc8d rescue cell lines data associated with main Figure 1</p>
<p>TIDE analysis and tumor growth curves of Kaplan Meyer survival graphs shown in main Figure 3</p>
<p>Pt-drug treatment of polyclonal cell lines with wild type as well Lrrc8a or Lrrc8d knockout alleles shows positive selection for alleles</p>
<p>Analysis of publicly available ovarian cancer dataset to identify the association LRRC8A or LRRC8D expression with outcome chemotherapy cisplatin</p>
<p>Lrrc8d KO mice tolerate higher cisplatin doses than wild type mice</p>
<p>Lrrc8d KO mice tolerate higher cisplatin doses than wild type mice</p>
<p>Analysis of publicly available ovarian cancer dataset to identify the association LRRC8A or LRRC8D expression with outcome chemotherapy cisplatin</p>
<p>TIDE analysis and tumor growth curves of Kaplan Meyer survival graphs shown in main Figure 3</p>
<p>Primer sequences used for Lrrc8a or Lrrc8d knockout control in 2D cell lines mice reconstitution experiments</p>
<p>Blasticidin and Pt treatment of Lrrc8a or Lrrc8d rescue cell lines data associated with main Figure 1</p>
<p>Pt-drug treatment of polyclonal cell lines with wild type as well Lrrc8a or Lrrc8d knockout alleles shows positive selection for alleles</p>
<p>gRNA oligos used for the generation of Lrrc8a or Lrrc8d-knockout cell lines, organoids and tumors</p>
<p>Generation of monoclonal knockout cell lines Lrrc8a or Lrrc8d used in main Figure</p>