ORCID Profile
0000-0001-8766-6267
Current Organisations
University of Adelaide
,
AstraZeneca FoU Göteborg
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Publisher: American Physical Society (APS)
Date: 20-02-2013
Publisher: Cold Spring Harbor Laboratory
Date: 15-10-2017
Abstract: Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas G12D in mouse lung epithelial cells markedly impairs the progression of KRas G12D -driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas G12D -driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer.
Publisher: Springer Science and Business Media LLC
Date: 16-10-2017
DOI: 10.1038/NMETH.4466
Abstract: Pooled CRISPR screens are a powerful tool for assessments of gene function. However, conventional analysis is based exclusively on the relative abundance of integrated single guide RNAs (sgRNAs) between populations, which does not discern distinct phenotypes and editing outcomes generated by identical sgRNAs. Here we present CRISPR-UMI, a single-cell lineage-tracing methodology for pooled screening to account for cell heterogeneity. We generated complex sgRNA libraries with unique molecular identifiers (UMIs) that allowed for screening of clonally expanded, in idually tagged cells. A proof-of-principle CRISPR-UMI negative-selection screen provided increased sensitivity and robustness compared with conventional analysis by accounting for underlying cellular and editing-outcome heterogeneity and detection of outlier clones. Furthermore, a CRISPR-UMI positive-selection screen uncovered new roadblocks in reprogramming mouse embryonic fibroblasts as pluripotent stem cells, distinguishing reprogramming frequency and speed (i.e., effect size and probability). CRISPR-UMI boosts the predictive power, sensitivity, and information content of pooled CRISPR screens.
Publisher: American Physical Society (APS)
Date: 26-04-2022
Publisher: American Physical Society (APS)
Date: 11-01-2021
Publisher: IOP Publishing
Date: 02-2010
Publisher: American Physical Society (APS)
Date: 04-05-2020
Publisher: Springer Science and Business Media LLC
Date: 20-04-2023
Publisher: American Physical Society (APS)
Date: 28-08-2019
Publisher: Springer Science and Business Media LLC
Date: 29-09-2020
DOI: 10.1038/S41467-020-18548-9
Abstract: The CRISPR-Cas9 system has increased the speed and precision of genetic editing in cells and animals. However, model generation for drug development is still expensive and time-consuming, demanding more target flexibility and faster turnaround times with high reproducibility. The generation of a tightly controlled ObLiGaRe doxycycline inducible SpCas9 (ODInCas9) transgene and its use in targeted ObLiGaRe results in functional integration into both human and mouse cells culminating in the generation of the ODInCas9 mouse. Genomic editing can be performed in cells of various tissue origins without any detectable gene editing in the absence of doxycycline. Somatic in vivo editing can model non-small cell lung cancer (NSCLC) adenocarcinomas, enabling treatment studies to validate the efficacy of candidate drugs. The ODInCas9 mouse allows robust and tunable genome editing granting flexibility, speed and uniformity at less cost, leading to high throughput and practical preclinical in vivo therapeutic testing.
Publisher: IOP Publishing
Date: 30-11-2011
Publisher: OSA
Date: 2018
Publisher: The Optical Society
Date: 14-12-2017
Publisher: Springer Science and Business Media LLC
Date: 26-09-2016
DOI: 10.1038/SREP34101
Abstract: This work describes the first observations of the ionisation of neon in a metastable atomic state utilising a strong-field, few-cycle light pulse. We compare the observations to theoretical predictions based on the Ammosov-Delone-Krainov (ADK) theory and a solution to the time-dependent Schrödinger equation (TDSE). The TDSE provides better agreement with the experimental data than the ADK theory. We optically pump the target atomic species and measure the ionisation rate as the a function of different steady-state populations in the fine structure of the target state which shows significant ionisation rate dependence on populations of spin-polarised states. The physical mechanism for this effect is unknown.
Publisher: Elsevier BV
Date: 03-2018
Publisher: SPIE
Date: 30-12-2019
DOI: 10.1117/12.2541232
Publisher: AIP Publishing
Date: 07-2007
DOI: 10.1063/1.2754444
Abstract: We present a new technique to measure absolute total collision cross sections from metastable neon atoms. The technique is based on the observation of the decay rate of trapped atoms as they collide with room temperature atoms. We present the first measurement of this kind using trapped neon atoms in the P23 metastable state colliding with thermal ground state argon. The measured cross section has a value of 556±26Å2.
Publisher: American Physical Society (APS)
Date: 28-10-2008
Publisher: Optica Publishing Group
Date: 07-05-2010
DOI: 10.1364/OL.35.001653
Publisher: The Optical Society
Date: 02-04-2015
Publisher: American Physical Society (APS)
Date: 31-08-2018
No related grants have been discovered for roberto nitsch.