Ágnes Holczbauer

Mono-ADP-ribosylation-driven immunosuppression and cross-resistance to therapy through cancer cell intrinsic and extrinsic mechanisms

Yuchen Sun, Yingying Tang, Vivek T. Singh, Ágnes Holczbauer et autres

Mono-ADP-ribosylation (MARylation) is emerging as an important regulator of anti-cancer immunity and immunosuppressive tumor microenvironment (TME). Our previous studies showed that PARP11, one of several enzymes that facilitate MARylation, regulates the activities of intratumoral cytotoxic T lymphocytes (CTLs) and regulatory T cells …

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SPTBN2 promotes an immunosuppressive tumor microenvironment and cross-resistance to anti-cancer therapies

Quoc Thang Bui, Raghavendra Basavaraja, Mayura Dhamdhere, Ágnes Holczbauer et autres

Immunosuppressive tumor microenvironment (TME) inactivates CD8+ cytotoxic lymphocytes (CTLs). Here, we identify SPTBN2 spectrin as a key immunosuppressive regulator induced in CTLs in response to nutritional deficit. In human pancreatic and colorectal cancers, SPTBN2 expression negatively correlated with CTL infiltration and patients' …

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PARP11 inhibition inactivates tumor-infiltrating regulatory T cells and improves the efficacy of immunotherapies

Raghavendra Basavaraja, Hongru Zhang, Ágnes Holczbauer, Zhen Lu et autres

Tumor-infiltrating regulatory T cells (TI-Tregs) elicit immunosuppressive effects in the tumor microenvironment (TME) leading to accelerated tumor growth and resistance to immunotherapies against solid tumors. Here, we demonstrate that poly-(ADP-ribose)-polymerase-11 (PARP11) is an essential regulator of immunosuppressive activities of TI-Tregs. Expression of …

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Evolutionary conservation of the fidelity of transcription

Claire Chung, Bert M. Verheijen, Zoe Navapanich, Eric McGann et autres

Abstract Accurate transcription is required for the faithful expression of genetic information. However, relatively little is known about the molecular mechanisms that control the fidelity of transcription, or the conservation of these mechanisms across the tree of life. To address these issues, …

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MYC and MET cooperatively drive hepatocellular carcinoma with distinct molecular traits and vulnerabilities

Celia Sequera, Margherita Grattarola, Ágnes Holczbauer, Rosanna Dono et autres

Abstract Enhanced activation of the transcription factor MYC and of the receptor tyrosine kinase MET are among the events frequently occurring in hepatocellular carcinoma (HCC). Both genes individually act as drivers of liver cancer initiation and progression. However, their concomitant alteration in …

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MYC and MET cooperatively drive hepatocellular carcinoma with distinct molecular traits and vulnerabilities

Celia Sequera, Margherita Grattarola, Ágnes Holczbauer, Rosanna Dono et autres

Abstract Enhanced activation of the transcription factor MYC and of the receptor tyrosine kinase MET are among events frequently occurring in hepatocellular carcinoma (HCC). Both genes individually act as drivers of liver cancer initiation and progression. However, their concomitant alteration in HCC …

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Evolutionary conservation of the fidelity of transcription

Claire Chung, Eric McGann, Lambertus Verheijen, Zoe Navapanich et autres

Abstract Accurate transcription is required for the faithful expression of genetic information. Surprisingly though, little is known about the molecular mechanisms that control the fidelity of transcription, or the conservation of these mechanisms across the tree of life. To address this issue, …

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In Vivo Screen Identifies Liver X Receptor Alpha Agonism Potentiates Sorafenib Killing of Hepatocellular Carcinoma

Alexandra M. Vázquez-Salgado, Morgan Preziosi, Dali Yin, Ágnes Holczbauer et autres

Hepatocellular carcinoma (HCC) is the most prevalent cancer of the liver and is a leading cause of cancer deaths worldwide. The multikinase inhibitor sorafenib has long been used to treat HCC because it was shown to extend survival by 3 months.1 Although …

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Cellular origins of regenerating liver and hepatocellular carcinoma

Ágnes Holczbauer, Kirk J. Wangensteen, Soona Shin

Hepatocellular carcinoma (HCC) is the predominant primary cancer arising from the liver and is one of the major causes of cancer-related mortality worldwide. The cellular origin of HCC has been a topic of great interest due to conflicting findings regarding whether it …

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Transcription errors induce proteotoxic stress and shorten cellular lifespan

M. Arthur Moseley, Dorothy A. Erie, George L. Sutphin, J. Will Thompson et autres

Transcription errors occur in all living cells; however, it is unknown how these errors affect cellular health. To answer this question, we monitored yeast cells that were genetically engineered to display error-prone transcription. We discovered that these cells suffer from a profound …

P-A2 Towards curtailing HIV latency by combinatorial unblocking viral transcription

Suresh K. Arya, Ágnes Holczbauer

The idea that it may be possible to “cure” AIDS is beginning to be accepted. Whether that is realistic or a pipe dream remains to be seen. The impediment is HIV latency. Thinking is that (1) if we could wake up the …

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Correction: Corrigendum: Transcription errors induce proteotoxic stress and shorten cellular lifespan

Marc Vermulst, Ashley S. Denney, Michael J. Lang, Chao-Wei Hung et autres

Nature Communications 6, Article number: 8065 (2015); Published 25 August 2015; Updated 14 October 2015 The original version of this Article contained an error in the spelling of the authors J. Will Thompson and M. Arthur Moseley, which were incorrectly given as …

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