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22 results on '"Kiourtis, Christos"'

1. Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ

Author

Kiourtis, Christos, Terradas-Terradas, Maria, Gee, Lucy M., May, Stephanie, Georgakopoulou, Anastasia, Collins, Amy L., O’Sullivan, Eoin D., Baird, David P., Hassan, Mohsin, Shaw, Robin, Tan, Ee Hong, Müller, Miryam, Engelmann, Cornelius, Andreola, Fausto, Hsieh, Ya-Ching, Reed, Lee H., Borthwick, Lee A., Nixon, Colin, Clark, William, Hanson, Peter S., Sumpton, David, Mackay, Gillian, Suzuki, Toshiyasu, Najumudeen, Arafath K., Inman, Gareth J., Campbell, Andrew, Barry, Simon T., Quaglia, Alberto, Morris, Christopher M., LeBeau, Fiona E. N., Sansom, Owen J., Kirschner, Kristina, Jalan, Rajiv, Oakley, Fiona, and Bird, Thomas G.

Published
2024
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2. A study on the systemic transmission of cellular senescence and its role in acute liver failure

Author

Kiourtis, Christos

Abstract

Cellular senescence is a stress response observed in a wide range of pathologies. Its cytostatic properties make senescence an inhibitor of normal repair and regeneration after tissue injury. Senescence has been reported to have a negative effect on several diseases of the liver including acute liver failure, a rare but deadly disease. In this disease, senescence has been shown to block proper regeneration following acute liver injury and this has been associated with a worse prognosis. Acute liver failure is a syndrome that also affects numerous extra hepatic organs, including the kidneys, the brain and the lung. This multi-organ failure presents a clinical challenge as it occurs in more than 50% of acute liver failure patients, its etiology remains largely unknown and supportive care, using organ support e.g. ventilation and haemofiltration, is the main way of managing it. Senescent cells produce and secrete a diverse set of factors that can have various effects on the microenvironment of these cells. One effect of these factors is the transmission of senescence to nearby healthy cells, resulting in the propagation of the senescent phenotype. This phenomenon has been described both in cell culture as well as in mouse models. More specifically, work by us has revealed that senescent hepatocytes are able to induce a senescent phenotype to neighbouring non-senescent hepatocytes in a paracrine, TGFβ-dependent manner. Given the development of hepatic senescence and multi-organ failure during acute liver failure, in my project I sought to investigate a potential systemic transmission of senescence from the liver to other organs, particularly in the extra-hepatic organs affected during acute liver failure. To do this I first characterised a mouse model of hepatocyte-specific induction of senescence. After establishing widespread liver senescence in this model, I then examined whether systemic transmission of senescence occurs in this model. I observed the development of renal, brain and lung senescence, accompanied by elements of renal dysfunction, repair and reprogramming following the induction of liver senescence. Further investigation using other mouse models as well as in vitro approaches revealed that systemic transmission of senescence is dependent on an active TGFβ signalling pathway. Inhibition of this pathway resulted in the prevention of senescence transmission both in vitro and in vivo, reduced the degree of renal repair and reprogramming in vivo and improved organ function. In conclusion, these data provide evidence for the in vivo spread of senescence between organs. To our knowledge, this is the first time this phenotype is reported using a highly specific model of senescence induction. In the long term, this work may benefit the treatment of acute liver failure patients by providing potential new therapies for this disease.

Published
2021
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3. Absent expansion of AXIN2+ hepatocytes and altered physiology in Axin2CreERT2 mice challenges the role of pericentral hepatocytes in homeostatic liver regeneration

Author

May, Stephanie, Müller, Miryam, Livingstone, Callum R., Skalka, George L., Walsh, Peter J., Nixon, Colin, Hedley, Ann, Shaw, Robin, Clark, William, Vande Voorde, Johan, Officer-Jones, Leah, Ballantyne, Fiona, Powley, Ian R., Drake, Thomas M., Kiourtis, Christos, Keith, Andrew, Rocha, Ana Sofia, Tardito, Saverio, Sumpton, David, Le Quesne, John, Bushell, Martin, Sansom, Owen J., and Bird, Thomas G.

Published
2023
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4. Anti–Cholestatic Therapy with Obeticholic Acid Improves Short-Term Memory in Bile Duct–Ligated Mice

Author

Gee, Lucy M.V., Barron-Millar, Ben, Leslie, Jack, Richardson, Claire, Zaki, Marco Y.W., Luli, Saimir, Burgoyne, Rachel A., Cameron, Rainie I.T., Smith, Graham R., Brain, John G., Innes, Barbara, Jopson, Laura, Dyson, Jessica K., McKay, Katherine R.C., Pechlivanis, Alexandros, Holmes, Elaine, Berlinguer-Palmini, Rolando, Victorelli, Stella, Mells, George F., Sandford, Richard N., Palmer, Jeremy, Kirby, John A., Kiourtis, Christos, Mokochinski, Joao, Hall, Zoe, Bird, Thomas G., Borthwick, Lee A., Morris, Christopher M., Hanson, Peter S., Jurk, Diana, Stoll, Elizabeth A., LeBeau, Fiona E.N., Jones, David E.J., and Oakley, Fiona

Published
2023
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7. Contributors

Author

Abid, Shariq, primary, Adnot, Serge, additional, Agusti, Alvar, additional, Beaulieu, Delphine, additional, Bhushan, Anil, additional, Bird, Thomas G., additional, Born, Emmanuelle, additional, Breau, Marielle, additional, Chin, Alexander F., additional, Elisseeff, Jennifer H., additional, Erlangga, Zulrahman, additional, Evangelou, Konstantinos, additional, Faner, Rosa, additional, Farr, Joshua N., additional, Georgakopoulou, Eleni, additional, González-Gualda, Estela, additional, Gorgoulis, Vassilis G., additional, Gray-Gaillard, Elise, additional, Han, Jin, additional, Hernandez-Gonzalez, Fernanda, additional, Houssaini, Amal, additional, Jensen, Michael D., additional, Jurk, Diana, additional, Katsuumi, Goro, additional, Khosla, Sundeep, additional, Kiourtis, Christos, additional, Kirkland, James L., additional, Kovatcheva, Marta, additional, Lipskaia, Larissa, additional, López-Domínguez, Jose Alberto, additional, Macías, David, additional, Marcos, Elisabeth, additional, Maus, Mate, additional, Melk, Anette, additional, Meyer, Kathleen, additional, Michel, John, additional, Minamino, Tohru, additional, Miwa, Satomi, additional, Monroe, David G., additional, Muñoz-Espín, Daniel, additional, Ou, Hui-Ling, additional, Palmer, Allyson K., additional, Saito, Nayuta, additional, Schmitt, Roland, additional, Sellares, Jacobo, additional, Serrano, Manuel, additional, Sung, Myong-Hee, additional, Tchkonia, Tamara, additional, Thompson, Peter J., additional, von Zglinicki, Thomas, additional, Wan, Tengfei, additional, and Zhang, Peisu, additional

Published
2022
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9. Human-correlated genetic HCC models identify combination therapy for precision medicine

Author

Müller, Miryam, primary, May, Stephanie, additional, Hall, Holly, additional, Kendall, Timothy J., additional, McGarry, Lynn, additional, Blukacz, Lauriane, additional, Nuciforo, Sandro, additional, Jamieson, Thomas, additional, Phinichkusolchit, Narisa, additional, Dhayade, Sandeep, additional, Leslie, Jack, additional, Sprangers, Joep, additional, Malviya, Gaurav, additional, Mrowinska, Agata, additional, Johnson, Emma, additional, McCain, Misti, additional, Halpin, John, additional, Kiourtis, Christos, additional, Georgakopoulou, Anastasia, additional, Nixon, Colin, additional, Clark, William, additional, Shaw, Robin, additional, Hedley, Ann, additional, Drake, Thomas M., additional, Tan, Ee Hong, additional, Neilson, Matt, additional, Murphy, Daniel J., additional, Lewis, David, additional, Reeves, Helen L., additional, Mann, Derek A., additional, Blyth, Karen, additional, Heim, Markus H., additional, Carlin, Leo M., additional, Sansom, Owen J., additional, Miller, Crispin, additional, and Bird, Thomas G., additional

Published
2022
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10. A noninvasive iRFP713 p53 reporter reveals dynamic p53 activity in response to irradiation and liver regeneration in vivo

Author

Humpton, Timothy J., primary, Hock, Andreas K., additional, Kiourtis, Christos, additional, De Donatis, Marco, additional, Fercoq, Frédéric, additional, Nixon, Colin, additional, Bryson, Sheila, additional, Strathdee, Douglas, additional, Carlin, Leo M., additional, Bird, Thomas G., additional, Blyth, Karen, additional, and Vousden, Karen H., additional

Published
2022
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11. Inter-organ transmission of hepatocellular senescence induces multi-organ dysfunction through the TGFβ signalling pathway.

Author

Bird, Thomas, primary, Kiourtis, Christos, additional, Terradas, Maria Terradas, additional, Gee, Lucy, additional, Hsieh, Ya-Ching, additional, Clark, William, additional, Nixon, Colin, additional, Shaw, Robin, additional, Sumpton, David, additional, Mackay, Gillian, additional, May, Stephanie, additional, Müller, Miryam, additional, Campbell, Andrew, additional, Barry, Simon, additional, Lebeau, Fiona, additional, Sansom, Owen, additional, Kirschner, Kristina, additional, Oakley, Fiona, additional, Hanson, Peter, additional, Najumudeen, Arafath, additional, and Morris, Christopher, additional

Published
2021
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14. Autophagy suppresses the formation of hepatocyte-derived cancer-initiating ductular progenitor cells in the liver

Author

Barthet, Valentin J. A., primary, Brucoli, Martina, additional, Ladds, Marcus J. G. W., additional, Nössing, Christoph, additional, Kiourtis, Christos, additional, Baudot, Alice D., additional, O’Prey, James, additional, Zunino, Barbara, additional, Müller, Miryam, additional, May, Stephanie, additional, Nixon, Colin, additional, Long, Jaclyn S., additional, Bird, Thomas G., additional, and Ryan, Kevin M., additional

Published
2021
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16. Notch Signaling Mediates Secondary Senescence

Author

Teo, Yee Voan, Rattanavirotkul, Nattaphong, Olova, Nelly, Salzano, Angela, Quintanilla, Andrea, Tarrats, Nuria, Kiourtis, Christos, Müller, Miryam, Green, Anthony R., Adams, Peter D., Acosta, Juan-Carlos, Bird, Thomas G., Kirschner, Kristina, Neretti, Nicola, and Chandra, Tamir

Published
2019
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17. Absent expansion of pericentral hepatocytes and altered physiology in Axin2CreERT2 mice

Author

May, Stephanie, primary, Müller, Miryam, additional, Livingstone, Callum R, additional, Skalka, George, additional, Nixon, Colin, additional, Hedley, Ann, additional, Shaw, Robin, additional, Clark, William, additional, Drake, Thomas M, additional, Kiourtis, Christos, additional, Rocha, Ana Sofia, additional, Sansom, Owen J, additional, and Bird, Thomas G, additional

Published
2020
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18. Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence

Author

Vizioli, Maria Grazia, primary, Liu, Tianhui, additional, Miller, Karl N., additional, Robertson, Neil A., additional, Gilroy, Kathryn, additional, Lagnado, Anthony B., additional, Perez-Garcia, Arantxa, additional, Kiourtis, Christos, additional, Dasgupta, Nirmalya, additional, Lei, Xue, additional, Kruger, Patrick J., additional, Nixon, Colin, additional, Clark, William, additional, Jurk, Diana, additional, Bird, Thomas G., additional, Passos, João F., additional, Berger, Shelley L., additional, Dou, Zhixun, additional, and Adams, Peter D., additional

Published
2020
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20. Notch signalling mediates secondary senescence

Author

Teo, Yee Voan, primary, Rattanavirotkul, Nattaphong, additional, Salzano, Angela, additional, Quintanilla, Andrea, additional, Tarrats, Nuria, additional, Kiourtis, Christos, additional, Mueller, Miryam, additional, Green, Anthony R., additional, Adams, Peter D., additional, Acosta, Juan-Carlos, additional, Bird, Thomas G., additional, Kirschner, Kristina, additional, Neretti, Nicola, additional, and Chandra, Tamir, additional

Published
2019
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21. TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence

Author

Bird, Thomas G., primary, Müller, Miryam, additional, Boulter, Luke, additional, Vincent, David F., additional, Ridgway, Rachel A., additional, Lopez-Guadamillas, Elena, additional, Lu, Wei-Yu, additional, Jamieson, Thomas, additional, Govaere, Olivier, additional, Campbell, Andrew D., additional, Ferreira-Gonzalez, Sofía, additional, Cole, Alicia M., additional, Hay, Trevor, additional, Simpson, Kenneth J., additional, Clark, William, additional, Hedley, Ann, additional, Clarke, Mairi, additional, Gentaz, Pauline, additional, Nixon, Colin, additional, Bryce, Steven, additional, Kiourtis, Christos, additional, Sprangers, Joep, additional, Nibbs, Robert J. B., additional, Van Rooijen, Nico, additional, Bartholin, Laurent, additional, McGreal, Steven R., additional, Apte, Udayan, additional, Barry, Simon T., additional, Iredale, John P., additional, Clarke, Alan R., additional, Serrano, Manuel, additional, Roskams, Tania A., additional, Sansom, Owen J., additional, and Forbes, Stuart J., additional

Published
2018
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22. Secondary and a Subset of Primary Senescent Cells Result from Notch Signalling

Author

Teo, Yee Voan, primary, Rattanavirotkul, Nattaphong, additional, Salzano, Angela, additional, Quintanilla, Andrea, additional, Tarrats, Nuria, additional, Kiourtis, Christos, additional, Mueller, Miryam, additional, Green, Anthony R., additional, Adams, Peter D., additional, Acosta, Juan-Carlos, additional, Bird, Thomas G., additional, Kirschner, Kristina, additional, Neretti, Nicola, additional, and Chandra, Tamir, additional

Published
2018
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