Publications de Andrea Ablasser

Regulation of the cGAS-STING Pathway

Andrea Ablasser, Pengbiao Xu, Bing Zhang

The cGAS-cGAMP-STING pathway is essential for immune defense against pathogens. Upon binding DNA, cGAS synthesizes cGAMP, which activates STING, leading to potent innate immune effector responses. However, lacking specific features to distinguish between s ...

Annual Reviews2025

The crl5spsb3 ubiquitin ligase targets nuclear cgas for degradation

Andrea Ablasser, Pengbiao Xu, Lingyun Li

The present invention relates to a variant of cyclic GMP-AMP synthase (cGAS) carrying an amino acid substitution at one or more of (i) asparagine at amino acid position 513, (ii) asparagine at amino acid position 514, (iii) aspartic acid at amino acid posi ...

2024

The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation

Andrea Ablasser, Baptiste Claude André Guey, Jonathan Jean-Pierre Ricci, Pauline Ambre Melenec, Ying Liu, Pengbiao Xu, Chong Liu, Lingyun Li

Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2 ' 3 '-cyclic GMP-AMP (cGAMP)1-7. The indiscriminate activity of cGAS towards DNA d ...

Nature Portfolio2024

cGAS-STING drives ageing-related inflammation and neurodegeneration

Bastien Mangeat, Natasha Ella Samson, Andrea Ablasser, Muhammet Fatih Gülen, Sélène-Véronique Glück, Vivek Vijay Thacker, Chong Liu

Low-grade inflammation is a hallmark of old age and a central driver of ageing-associated impairment and disease(1). Multiple factors can contribute to ageing-associated inflammation(2); however, the molecular pathways that transduce aberrant inflammatory ...

2023

Cgas super-enzymes for cancer immunotherapy

Natasha Ella Samson, Andrea Ablasser

The present invention relates to anti-tumor lymphocytes, and a variant cyclic GMP-AMP synthase (cGAS) carrying an amino acid substitution of one or both arginines at amino acid positions 255 and 236 and/or an amino acid substitution of one or both lysines ...

2023

The cGAS–STING pathway drives type I IFN immunopathology in COVID-19

Kunal Sharma, Andrea Ablasser, Muhammet Fatih Gülen, Vivek Vijay Thacker, Théo Nass, Martin Schaller

COVID-19, which is caused by infection with SARS-CoV-2, is characterized by lung pathology and extrapulmonary complications1,2. Type I interferons (IFNs) have an essential role in the pathogenesis of COVID-19 (refs 3–5). Although rapid induction of type I ...

2022

Emerging dimensions of cellular cGAS-STING signaling

Andrea Ablasser, Baptiste Claude André Guey

The recognition of DNA through the cGAS-STING pathway plays a critical role in antiviral immunity, but can also drive maladaptive immune responses underlying several pathological conditions. Despite its importance, understanding the organization of cGAS-ST ...

2022

The cGAS-STING pathway and cancer

Natasha Ella Samson, Andrea Ablasser

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has emerged as a critical innate immune pathway that, following engagement by DNA, promotes distinct immune effector responses that can impact virtually all aspects of tumori ...

NATURE PORTFOLIO2022

Clathrin-associated AP-1 control stermination of STING signalling

Sophie Marie Elisabeth Rivara, Andrea Ablasser, Jonathan Jean-Pierre Ricci, Ying Liu, Pengbiao Xu, Chong Liu

Stimulator of interferon genes (STING) functions downstream of cyclic GMP-AMP synthase in DNA sensing or as a direct receptor for bacterial cyclic dinucleotides and small molecules to activate immunity during infection, cancer and immunotherapy(1-10). Prec ...

NATURE PORTFOLIO2022

Monocyte-derived macrophages aggravate pulmonary vasculitis via cGAS/STING/IFN-mediated nucleic acid sensing

Andrea Ablasser

Kessler et al. identify aberrant DNA recognition by cGAS/STING and IFN-I production by inflammatory macrophages as a driver of severe ANCA-associated vasculitis. Pharmacological interventions blocking this pathway ameliorate disease and accelerate recovery ...

ROCKEFELLER UNIV PRESS2022

Colon tumour cell death causes mTOR dependence by paracrine P2X4 stimulation

Andrea Ablasser

Solid cancers exhibit a dynamic balance between cell death and proliferation ensuring continuous tumour maintenance and growth(1,2). Increasing evidence links enhanced cancer cell apoptosis to paracrine activation of cells in the tumour microenvironment in ...

NATURE PORTFOLIO2022

STING-Inhibition after myocardial infarction

Andrea Ablasser

SPRINGER WIEN2021

Interplay of cGAS with chromatin

Andrea Ablasser, Marilena Wischnewski

Recognition of DNA is an evolutionarily highly conserved mechanism of immunity. In mammals, the cGAS-STING pathway plays a central role in coupling DNA sensing to the execution of innate immune mechanisms, both in contexts of infection as well as in noninf ...

ELSEVIER SCIENCE LONDON2021

m6A methylation potentiates cytosolic dsDNA recognition in a sequence-specific manner

Andrea Ablasser, Muhammet Fatih Gülen

Nucleic acid sensing through pattern recognition receptors is critical for immune recognition of microbial infections. Microbial DNA is frequently methylated at the N-6 position of adenines (m6A), a modification that is rare in mammalian host DNA. We show ...

ROYAL SOC2021

DNA sensor in standby mode during mitosis

Andrea Ablasser

American Association for the Advancement of Science2021

The spatial organization of cGAS-TREX1 interactions

Andrea Ablasser, Paula Juricic Dzankic

Coupling DNA sensing to the initiation of immune responses necessitates auxiliary control mechanisms to avoid autoimmunity. A key factor is the exonuclease TREX1, which antagonizes DNA-mediated activation of cGAS. Two studies, by Mohr et al. (2021) and Zho ...

Cell Press - Elsevier2021

STING inhibition in myocardial remodelling following myocardial infarction

Andrea Ablasser

OXFORD UNIV PRESS2021

The cGAS-STING pathway as a therapeutic target in inflammatory diseases

Andrea Ablasser, Alexiane Clara Decout

The cGAS-STING pathway drives innate immune activation in response to cytosolic DNA. This is important for immunity to bacteria and viruses, but aberrant cGAS-STING activity is also linked to inflammatory disease. Here, Ablasser and colleagues discuss how ...

NATURE RESEARCH2021

DNA hypomethylation leads to cGAS-induced autoinflammation in the epidermis

Andrea Ablasser

DNA methylation is a fundamental epigenetic modification, important across biological processes. The maintenance methyltransferase DNMT1 is essential for lineage differentiation during development, but its functions in tissue homeostasis are incompletely u ...

WILEY2021

Editorial overview 'Network news: Reporting from the frontlines of cell signaling'

Andrea Ablasser

CURRENT BIOLOGY LTD2020