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1. A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease

Author

Lim, Kyungtae, Rutherford, Eimear N, Delpiano, Livia, He, Peng, Lin, Weimin, Sun, Dawei, Van den Boomen, Dick J H, Edgar, James R, Bang, Jae Hak, Predeus, Alexander, Teichmann, Sarah A, Marioni, John C, Matesic, Lydia E, Lee, Joo-Hyeon, Lehner, Paul J, Marciniak, Stefan J, Rawlins, Emma L, and Dickens, Jennifer A

Published
2025
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2. Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis

Author

Zhuang, Xueqian, Wang, Qing, Joost, Simon, Ferrena, Alexander, Humphreys, David T., Li, Zhuxuan, Blum, Melissa, Krause, Klavdija, Ding, Selena, Landais, Yuna, Zhan, Yingqian, Zhao, Yang, Chaligne, Ronan, Lee, Joo-Hyeon, Carrasco, Sebastian E., Bhanot, Umeshkumar K., Koche, Richard P., Bott, Matthew J., Katajisto, Pekka, Soto-Feliciano, Yadira M., Pisanic, Thomas, Thomas, Tiffany, Zheng, Deyou, Wong, Emily S., and Tammela, Tuomas

Published
2025
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7. Quantitative and qualitative mutational impact of ionizing radiation on normal cells

Author

Youk, Jeonghwan, Kwon, Hyun Woo, Lim, Joonoh, Kim, Eunji, Kim, Taewoo, Kim, Ryul, Park, Seongyeol, Yi, Kijong, Nam, Chang Hyun, Jeon, Sara, An, Yohan, Choi, Jinwook, Na, Hyelin, Lee, Eon-Seok, Cho, Youngwon, Min, Dong-Wook, Kim, HyoJin, Kang, Yeong-Rok, Choi, Si Ho, Bae, Min Ji, Lee, Chang Geun, Kim, Joon-Goon, Kim, Young Seo, Yu, Tosol, Lee, Won-Chul, Shin, Jong-Yeon, Lee, Dong Soo, Kim, Tae-You, Ku, Taeyun, Kim, Su Yeon, Lee, Joo-Hyeon, Koo, Bon-Kyoung, Lee, Hyunsook, Yi, On Vox, Han, Eon Chul, Chang, Ji Hyun, Kim, Kyung Su, Son, Tae Gen, and Ju, Young Seok

Published
2024
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8. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2

Author

Brevini, Teresa, Maes, Mailis, Webb, Gwilym J., John, Binu V., Fuchs, Claudia D., Buescher, Gustav, Wang, Lu, Griffiths, Chelsea, Brown, Marnie L., Scott, III, William E., Pereyra-Gerber, Pehuén, Gelson, William T. H., Brown, Stephanie, Dillon, Scott, Muraro, Daniele, Sharp, Jo, Neary, Megan, Box, Helen, Tatham, Lee, Stewart, James, Curley, Paul, Pertinez, Henry, Forrest, Sally, Mlcochova, Petra, Varankar, Sagar S., Darvish-Damavandi, Mahnaz, Mulcahy, Victoria L., Kuc, Rhoda E., Williams, Thomas L., Heslop, James A., Rossetti, Davide, Tysoe, Olivia C., Galanakis, Vasileios, Vila-Gonzalez, Marta, Crozier, Thomas W. M., Bargehr, Johannes, Sinha, Sanjay, Upponi, Sara S., Fear, Corrina, Swift, Lisa, Saeb-Parsy, Kourosh, Davies, Susan E., Wester, Axel, Hagström, Hannes, Melum, Espen, Clements, Darran, Humphreys, Peter, Herriott, Jo, Kijak, Edyta, Cox, Helen, Bramwell, Chloe, Valentijn, Anthony, Illingworth, Christopher J. R., Dahman, Bassam, Bastaich, Dustin R., Ferreira, Raphaella D., Marjot, Thomas, Barnes, Eleanor, Moon, Andrew M., Barritt, IV, Alfred S., Gupta, Ravindra K., Baker, Stephen, Davenport, Anthony P., Corbett, Gareth, Gorgoulis, Vassilis G., Buczacki, Simon J. A., Lee, Joo-Hyeon, Matheson, Nicholas J., Trauner, Michael, Fisher, Andrew J., Gibbs, Paul, Butler, Andrew J., Watson, Christopher J. E., Mells, George F., Dougan, Gordon, Owen, Andrew, Lohse, Ansgar W., Vallier, Ludovic, and Sampaziotis, Fotios

Published
2023
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9. Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Author

Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian’an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O’Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimäki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietiläinen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josée, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., and Tobin, Martin D.

Published
2023
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10. Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Author

Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian’an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O’Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimäki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietiläinen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josée, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., and Tobin, Martin D.

Published
2023
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11. SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity

Author

Baker, Stephen, Dougan, Gordon, Hess, Christoph, Kingston, Nathalie, Lehner, Paul J., Lyons, Paul A., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Summers, Charlotte, Thaventhiran, James E.D., Toshner, Mark, Weekes, Michael P., Maxwell, Patrick, Shaw, Ashley, Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Elmer, Anne, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, Mescia, Federica, O’Donnell, Ciara, Pointon, Linda, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Betancourt, Ariana, Bower, Georgie, Cossetti, Chiara, De Sa, Aloka, Epping, Madeline, Gleadall, Nick, Grenfell, Richard, Hinch, Andrew, Jackson, Sarah, Jarvis, Isobel, Krishna, Ben, Nice, Francesca, Omarjee, Ommar, Perera, Marianne, Potts, Martin, Richoz, Nathan, Romashova, Veronika, Stefanucci, Luca, Strezlecki, Mateusz, Turner, Lori, De Bie, Eckart M.D.D., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Allison, John, Butcher, Helen, Caputo, Daniela, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Graves, Barbara, Gray, Jennifer, Ivers, Tasmin, Le Gresley, Emma, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer, Scholtes, Ingrid, Hein, Sabine, King, Rebecca, Meng, Bo, Datir, Rawlings, Choi, Jinwook, Bradley, John R., Smith, Kenneth G.C., Lee, Joo Hyeon, and Gupta, Ravindra K.

Published
2022
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13. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

Author

Meng, Bo, Abdullahi, Adam, Ferreira, Isabella A. T. M., Goonawardane, Niluka, Saito, Akatsuki, Kimura, Izumi, Yamasoba, Daichi, Gerber, Pehuén Pereyra, Fatihi, Saman, Rathore, Surabhi, Zepeda, Samantha K., Papa, Guido, Kemp, Steven A., Ikeda, Terumasa, Toyoda, Mako, Tan, Toong Seng, Kuramochi, Jin, Mitsunaga, Shigeki, Ueno, Takamasa, Shirakawa, Kotaro, Takaori-Kondo, Akifumi, Brevini, Teresa, Mallery, Donna L., Charles, Oscar J., Bowen, John E., Joshi, Anshu, Walls, Alexandra C., Jackson, Laurelle, Martin, Darren, Smith, Kenneth G. C., Bradley, John, Briggs, John A. G., Choi, Jinwook, Madissoon, Elo, Meyer, Kerstin B., Mlcochova, Petra, Ceron-Gutierrez, Lourdes, Doffinger, Rainer, Teichmann, Sarah A., Fisher, Andrew J., Pizzuto, Matteo S., de Marco, Anna, Corti, Davide, Hosmillo, Myra, Lee, Joo Hyeon, James, Leo C., Thukral, Lipi, Veesler, David, Sigal, Alex, Sampaziotis, Fotios, Goodfellow, Ian G., Matheson, Nicholas J., Sato, Kei, and Gupta, Ravindra K.

Published
2022
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14. Multi-terminal spin valve in a strong Rashba channel exhibiting three resistance states.

Author

Lee, Joo-Hyeon, Kim, Hyung-Jun, Chang, Joonyeon, Han, Suk Hee, Koo, Hyun Cheol, Sayed, Shehrin, Hong, Seokmin, and Datta, Supriyo

Abstract

In a strong spin-orbit interaction system, the existence of three resistance states were observed when two ferromagnetic (FM) contacts were used as current terminals while a separate normal metal contact pair was used as voltage terminals. This result is strikingly different from ordinary spin valve or magnetic tunnel junction devices, which have only two resistance states corresponding to parallel (RP) and antiparallel (RAP) alignments of the FM contacts. Our experimental results on a quantum well layer with a strong Rashba effect clearly exhibit unequal antiparallel states, i.e., RAP(1) > RP > RAP(2), up to room temperature. The three-states are observed without any degradation when the distance between the non-magnetic voltage probe and the ferromagnetic current probe was increased up to 1.6 mm.

Published
2018

16. Tracing oncogene-driven remodelling of the intestinal stem cell niche

Author

Yum, Min Kyu, Han, Seungmin, Fink, Juergen, Wu, Szu-Hsien Sam, Dabrowska, Catherine, Trendafilova, Teodora, Mustata, Roxana, Chatzelo, Lemonia, Azzarelli, Roberta, Pshenichnaya, Irina, Lee, Eunmin, England, Frances, Kim, Jong Kyoung, Strange, Daniel E., Philpott, Anna, Lee, Joo-Hyeon, Koo, Bon-Kyoung, and Simons, Benjamin D.

Subjects
Physiological aspects, Genetic aspects, Oncogenes -- Physiological aspects, Intestines -- Physiological aspects -- Genetic aspects, Stem cells -- Genetic aspects -- Physiological aspects
Abstract

Author(s): Min Kyu Yum [sup.1] [sup.2] , Seungmin Han [sup.1] [sup.2] , Juergen Fink [sup.2] , Szu-Hsien Sam Wu [sup.3] [sup.4] , Catherine Dabrowska [sup.2] [sup.5] , Teodora Trendafilova [sup.2] [...], Interactions between tumour cells and the surrounding microenvironment contribute to tumour progression, metastasis and recurrence.sup.1-3. Although mosaic analyses in Drosophila have advanced our understanding of such interactions.sup.4,5, it has been difficult to engineer parallel approaches in vertebrates. Here we present an oncogene-associated, multicolour reporter mouse model--the Red2Onco system--that allows differential tracing of mutant and wild-type cells in the same tissue. By applying this system to the small intestine, we show that oncogene-expressing mutant crypts alter the cellular organization of neighbouring wild-type crypts, thereby driving accelerated clonal drift. Crypts that express oncogenic KRAS or PI3K secrete BMP ligands that suppress local stem cell activity, while changes in PDGFR.sup.loCD81.sup.+ stromal cells induced by crypts with oncogenic PI3K alter the WNT signalling environment. Together, these results show how oncogene-driven paracrine remodelling creates a niche environment that is detrimental to the maintenance of wild-type tissue, promoting field transformation dominated by oncogenic clones. By inducing changes in surrounding tissue, mutant intestinal stem cells create an unfavourable niche environment that gives them a competitive advantage over non-mutant neighbours.

Published
2021
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19. Emergence of a High-Plasticity Cell State during Lung Cancer Evolution

Author

Marjanovic, Nemanja Despot, Hofree, Matan, Chan, Jason E., Canner, David, Wu, Katherine, Trakala, Marianna, Hartmann, Griffin G., Smith, Olivia C., Kim, Jonathan Y., Evans, Kelly Victoria, Hudson, Anna, Ashenberg, Orr, Porter, Caroline B.M., Bejnood, Alborz, Subramanian, Ayshwarya, Pitter, Kenneth, Yan, Yan, Delorey, Toni, Phillips, Devan R., Shah, Nisargbhai, Chaudhary, Ojasvi, Tsankov, Alexander, Hollmann, Travis, Rekhtman, Natasha, Massion, Pierre P., Poirier, John T., Mazutis, Linas, Li, Ruifang, Lee, Joo-Hyeon, Amon, Angelika, Rudin, Charles M., Jacks, Tyler, Regev, Aviv, and Tammela, Tuomas

Published
2020
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24. Adult mouse intralobar airway stem cells

Author

Dabrowska, Catherine, primary, Li, Jingyun, additional, Mulay, Apoorva, additional, Carraro, Gianni, additional, Gupta, Manav, additional, Kim, Carla F., additional, Lee, Joo-Hyeon, additional, and Stripp, Barry R., additional

Published
2021
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25. Metastatic-niche labelling reveals parenchymal cells with stem features

Author

Ombrato, Luigi, Nolan, Emma, Kurelac, Ivana, Mavousian, Antranik, Bridgeman, Victoria Louise, Heinze, Ivonne, Chakravarty, Probir, Horswell, Stuart, Gonzalez-Gualda, Estela, Matacchione, Giulia, Weston, Anne, Kirkpatrick, Joanna, Husain, Ehab, Speirs, Valerie, Collinson, Lucy, Ori, Alessandro, Lee, Joo-Hyeon, and Malanchi, Ilaria

Published
2019
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32. A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease

Author

Lim, Kyungtae, primary, Rutherford, Eimear N, additional, Sun, Dawei, additional, Van den Boomen, Dick JH, additional, Edgar, James R, additional, Bang, JaeHak, additional, Matesic, Lydia E, additional, Lee, Joo-Hyeon, additional, Lehner, Paul J, additional, Marciniak, Stefan J, additional, Rawlins, Emma L, additional, and Dickens, Jennifer A, additional

Published
2023
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34. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2

Author

Brevini, Teresa, Maes, Mailis, Webb, Gwilym J, John, Binu V, Fuchs, Claudia D, Buescher, Gustav, Wang, Lu, Griffiths, Chelsea, Brown, Marnie L, Scott, William E, Pereyra-Gerber, Pehuén, Gelson, William TH, Brown, Stephanie, Dillon, Scott, Muraro, Daniele, Sharp, Jo, Neary, Megan, Box, Helen, Tatham, Lee, Stewart, James, Curley, Paul, Pertinez, Henry, Forrest, Sally, Mlcochova, Petra, Varankar, Sagar S, Darvish-Damavandi, Mahnaz, Mulcahy, Victoria L, Kuc, Rhoda E, Williams, Thomas L, Heslop, James A, Rossetti, Davide, Tysoe, Olivia C, Galanakis, Vasileios, Vila-Gonzalez, Marta, Crozier, Thomas WM, Bargehr, Johannes, Sinha, Sanjay, Upponi, Sara S, Fear, Corrina, Swift, Lisa, Saeb-Parsy, Kourosh, Davies, Susan E, Wester, Axel, Hagström, Hannes, Melum, Espen, Clements, Darran, Humphreys, Peter, Herriott, Jo, Kijak, Edyta, Cox, Helen, Bramwell, Chloe, Valentijn, Anthony, Illingworth, Christopher, UK-PBC Consortium, Dahman, Bassam, Bastaich, Dustin R, Ferreira, Raphaella D, Marjot, Thomas, Barnes, Eleanor, Moon, Andrew M, Barritt, Alfred S, Gupta, Ravindra K, Baker, Stephen, Davenport, Anthony P, Corbett, Gareth, Gorgoulis, Vassilis G, Buczacki, Simon JA, Lee, Joo-Hyeon, Matheson, Nicholas J, Trauner, Michael, Fisher, Andrew J, Gibbs, Paul, Butler, Andrew J, Watson, Christopher JE, Mells, George F, Dougan, Gordon, Owen, Andrew, Lohse, Ansgar W, Vallier, Ludovic, Sampaziotis, Fotios, Brevini, Teresa [0000-0002-3581-5379], Maes, Mailis [0000-0002-0266-6557], Wang, Lu [0000-0002-4418-8602], Brown, Marnie L [0000-0001-6463-0288], Scott, William E [0000-0003-1515-0514], Sharp, Jo [0000-0001-8482-5736], Neary, Megan [0000-0002-4960-2139], Tatham, Lee [0000-0001-9448-8876], Stewart, James [0000-0002-8928-2037], Darvish-Damavandi, Mahnaz [0000-0003-0226-2621], Williams, Thomas L [0000-0002-1051-0595], Crozier, Thomas WM [0000-0003-0951-4588], Bargehr, Johannes [0000-0002-9304-3573], Sinha, Sanjay [0000-0001-5900-1209], Saeb-Parsy, Kourosh [0000-0002-0633-3696], Wester, Axel [0000-0003-3634-6591], Melum, Espen [0000-0001-6903-6878], Bramwell, Chloe [0000-0001-8274-457X], Barnes, Eleanor [0000-0002-0860-0831], Moon, Andrew M [0000-0001-7163-2062], Gupta, Ravindra K [0000-0001-9751-1808], Baker, Stephen [0000-0003-1308-5755], Davenport, Anthony P [0000-0002-2096-3117], Gorgoulis, Vassilis G [0000-0001-9001-4112], Buczacki, Simon JA [0000-0002-2975-416X], Lee, Joo-Hyeon [0000-0002-7364-6422], Matheson, Nicholas J [0000-0002-3318-1851], Trauner, Michael [0000-0002-1275-6425], Fisher, Andrew J [0000-0003-4822-7223], Watson, Christopher JE [0000-0002-0590-4901], Owen, Andrew [0000-0002-9819-7651], Vallier, Ludovic [0000-0002-3848-2602], Sampaziotis, Fotios [0000-0003-0812-7586], and Apollo - University of Cambridge Repository

Subjects
Transcription, Genetic, SARS-CoV-2, Ursodeoxycholic Acid, COVID-19, Reproducibility of Results, COVID-19 Drug Treatment, Liver Transplantation, Organoids, Mice, Nasal Mucosa, Liver, Cricetinae, UK-PBC Consortium, Animals, Humans, Receptors, Virus, Angiotensin-Converting Enzyme 2, Registries, Lung, Retrospective Studies
Abstract

Acknowledgements: We thank the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Disease (AASLD) for supporting the COVID-Hep and SECURE-Liver registries; S. Marciniak and P. J. Lehner for comments and feedback on the manuscript; I. Goodfellow for providing the viral isolate; M. Wills and S. Clare for all their work ensuring a safe CL-3 working environment; C. Cormie for general lab support; the NIHR Cambridge BRC Cell Phenotyping Hub for their help with flow cytometry and processing of samples; the building staff of the Jeffrey Cheah Biomedical Centre for maintaining the institute open and safe during the period of lockdown; K. Füssel for coordinating the volunteer study and sample collection at the University Medical Centre Hamburg-Eppendorf; J. Hails, K.-I. Nikitopoulou and A. Ford for collecting blood samples; M. Colzani for advising on flow cytometry; A. Wiblin for advising on antibodies; and the Cambridge Biorepository for Translational Medicine for the provision of human tissue used in the study. T.B. was supported by an EASL Juan Rodès PhD fellowship. F.S. was supported by a UKRI Future Leaders fellowship, the Evelyn trust, an NIHR Clinical Lectureship, the Academy of Medical Sciences Starter Grant for Clinical Lecturers, the Addenbrooke’s Charitable Trust and the Rosetrees Trust. In addition, the F.S. laboratory is supported by the Cambridge University Hospitals National Institute for Health Research Biomedical Research Centre and the core support grant from the Wellcome Trust and Medical Research Council (MRC) of the Wellcome–Medical Research Council Cambridge Stem Cell Institute. The L.V. laboratory is funded by the ERC advanced grant New-Chol, the Cambridge University Hospitals National Institute for Health Research Biomedical Research Centre and the core support grant from the Wellcome Trust and MRC of the Wellcome–Medical Research Council Cambridge Stem Cell Institute. M.M., S.F. and G.D. are funded by the NIHR Cambridge Biomedical Research Centre and NIHR AMR Research Capital Funding Scheme (NIHR200640). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. V.L.M. was funded by an MRC Clinical Research Training Fellowship. G.F.M. was funded by a post-doctoral fellowship from the National Institute for Health Research (NIHR) Rare Diseases–Translational Research Collaboration (RD-TRC) and by an MRC Clinical Academic Research Partnership (CARP) award. The UK-PBC Nested Cohort study was funded by an MRC Stratified Medicine award (MR/L001489/1). C.J.R.I. was supported by the Medical Research Council (MC_UU_12014). T.M. is funded by a Wellcome Trust Clinical Research Training Fellowship (102176/B/13/Z). The A.P.D. laboratory was supported by BHF TG/18/4/33770, Wellcome Trust 203814/Z/16/A and Addenbrooke’s Charitable Trust. The COVID-Hep.net registry was supported by the European Association for the Study of the Liver (EASL) and the SECURE-Liver registry was supported by the American Association for the Study of Liver Disease (AASLD). The lung perfusion experiment was supported by the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation at Newcastle University and the University of Cambridge in partnership with NHS Blood and Transplant (NHSBT). The views expressed are those of the author(s) and not necessarily those of the NIHR, the Department of Health and Social Care or NHSBT. G.B. is funded by the European Reference Network for Hepatological Diseases (ERN RARE LIVER). A.O. acknowledges funding for preclinical research on treatment and prevention of COVID-19 from Unitaid (2020-38-LONGEVITY), the Engineering and Physical Sciences Research Council (EPSRC; EP/R024804/1), the Wellcome Trust (222489/Z/21/Z) and UK Research and Innovation (UKRI; BB/W010801/1). N.J.M. acknowledges funding from the MRC (CSF ref. MR/P008801/1 to N.J.M.), NHSBT (grant ref. WPA15-02 to N.J.M.) and Addenbrooke’s Charitable Trust (grant ref. to 900239 N.J.M.). This research was funded in whole, or in part, by the Wellcome Trust (203151/Z/16/Z, 203151/A/16/Z) and the UKRI Medical Research Council (MC_PC_17230). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission., Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.

Published
2022

37. A single cell atlas of in vitro multi-systems uncovers in vivo lineage trajectory and cell state in the human lung

Author

Kim, Jong-Il, primary, Lee, Woochan, additional, Lee, Seyoon, additional, Yoon, Jung-Ki, additional, Lee, Dakyung, additional, Kim, Yuri, additional, Han, Yeon Bi, additional, Kim, Rokhyun, additional, Moon, Sungji, additional, Park, Young Jun, additional, Park, Kyunghyuk, additional, Cha, Bukyoung, additional, Choi, Jaeyong, additional, Kim, Juhyun, additional, Ha, Na-young, additional, Kim, Kwhanmien, additional, Cho, Sukki, additional, Cho, Nam-Hyuk, additional, Desai, Tushar, additional, Chung, Jin-Haeng, additional, and Lee, Joo-Hyeon, additional

Published
2023
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38. CamouFAB: Real-Time Generation of Camouflage Pattern Using Optic Fiber Display

Author

Cho, Woon Jung, Yang, Jin-Hee, Kim, Hannah, Kang, Dong-Hyun, Kim, Min Sun, Lee, Ja Hyung, Kim, Yong-Jun, Lee, Joo-Hyeon, Han, Kwang-Hee, Junqueira Barbosa, Simone Diniz, editor, Chen, Phoebe, editor, Cuzzocrea, Alfredo, editor, Du, Xiaoyong, editor, Filipe, Joaquim, editor, Kara, Orhun, editor, Kotenko, Igor, editor, Sivalingam, Krishna M., editor, Ślęzak, Dominik, editor, Washio, Takashi, editor, Yang, Xiaokang, editor, and Stephanidis, Constantine, editor

Published
2014
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39. Red2Flpe-SCON: A Versatile, Multicolor Strategy for Generating Mosaic Conditional Knockout Mice

Author

Wu, Szu-Hsien Sam, primary, Kim, Somi, additional, Lee, Heetak, additional, Lee, Ji-Hyun, additional, Colozza, Gabriele, additional, Park, So-Yeon, additional, Bakonyi, Réka, additional, Teriyapirom, Isaree, additional, Hallay, Natalia, additional, Pilat-Carrota, Sandra, additional, Theussl, Hans-Christian, additional, Kim, Jihoon, additional, Lee, Joo-Hyeon, additional, Simons, Benjamin D., additional, Kim, Jong Kyoung, additional, and Koo, Bon-Kyoung, additional

Published
2023
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40. Bidirectional Activation of Stem-Like Programs between Metastatic Cancer and Alveolar Type 2 Cells within the Niche

Author

Rodrigues, Felipe, primary, Karoutas, Adam, additional, Rabas, Nicolas, additional, Ruhland, Stefanie, additional, Rizou, Tatiana, additional, Di Blasio, Stefania, additional, Bridgeman, Victoria L., additional, Ferreira, Rute M. M., additional, Goldstone, Robert, additional, Llorian Sopena, Miriam, additional, Lee, Joo-Hyeon, additional, Ombrato, Luigi, additional, and Malanchi, Ilaria, additional

Published
2023
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44. An Investigation of Usability Evaluation for Smart Clothing

Author

Chae, Haeng-Suk, Hong, Ji-Young, Cho, Hyun-Seung, Han, Kwang-Hee, Lee, Joo-Hyeon, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, and Jacko, Julie A., editor

Published
2007
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45. BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma

Author

Lazarus, Kyren A., Hadi, Fazal, Zambon, Elisabetta, Bach, Karsten, Santolla, Maria-Francesca, Watson, Julie K., Correia, Lucia L., Das, Madhumita, Ugur, Rosemary, Pensa, Sara, Becker, Lukas, Campos, Lia S., Ladds, Graham, Liu, Pentao, Evan, Gerard I., McCaughan, Frank M., Le Quesne, John, Lee, Joo-Hyeon, Calado, Dinis, and Khaled, Walid T.

Published
2018
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47. SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity

Author

Meng, Bo, Datir, Rawlings, Choi, Jinwook, CITIID-NIHR Bioresource COVID-19 Collaboration, Bradley, John R, Smith, Kenneth GC, Lee, Joo Hyeon, Gupta, Ravindra K, Lee, Joo [0000-0002-7364-6422], Gupta, Ravindra [0000-0001-9751-1808], and Apollo - University of Cambridge Repository

Subjects
Organoid, Omicron, SARS-CoV-2, Serine Endopeptidases, CP: Microbiology, COVID-19, spike, Virus Internalization, NTD, Delta, Spike Glycoprotein, Coronavirus, entry, Humans, fusogenicity, TMPRSS2
Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike N-terminal domain (NTD) remains poorly characterized despite enrichment of mutations in this region across variants of concern (VOCs). Here, we examine the contribution of the NTD to infection and cell-cell fusion by constructing chimeric spikes bearing B.1.617 lineage (Delta and Kappa variants) NTDs and generating spike pseudotyped lentivirus. We find that the Delta NTD on a Kappa or wild-type (WT) background increases S1/S2 cleavage efficiency and virus entry, specifically in lung cells and airway organoids, through use of TMPRSS2. Delta exhibits increased cell-cell fusogenicity that could be conferred to WT and Kappa spikes by Delta NTD transfer. However, chimeras of Omicron BA.1 and BA.2 spikes with a Delta NTD do not show more efficient TMPRSS2 use or fusogenicity. We conclude that the NTD allosterically modulates S1/S2 cleavage and spike-mediated functions in a spike context-dependent manner, and allosteric interactions may be lost when combining regions from more distantly related VOCs.

Published
2022
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