Our laboratory focuses on understanding mechanisms of diseases associated to the digestive system, with a special focus on liver and intestinal diseases. By employing multi- and inter-disciplinary approaches, including the use of mouse models mimicking human disease combined with human data, we aim to: find out what goes wrong in diseased and cancerous tissues; understand how organs can regenerate; potentially engineer new tissues; and, if regeneration goes awry, determine how it contributes to cancer.
Our interest is mainly driven by the discovery of two components initially identified in our laboratory to be downstream targets of the growth factor and nutrient signalling cascades: the URI (Unconventional prefoldin RPB5 Interactor) and MCRS1 (Microspherule protein 1) proteins. URI and MCRS1 expression turned out to be regulated in response to various environmental factors (radiation, nutrients, bacteria, viruses, etc.), compromising their functions and activating pleiotropic circuits to support complex cell signalling networks, provoking severe outcomes. Importantly, URI and MCRS1 are respectively part of 2 independent protein complexes: the URI prefoldin-like and the non-specific lethal (NSL) complexes. While URI might have some co-chaperone activities to maintain proteostasis, we identified MCRS1 to be a new regulator of histone acetylation and, therefore, a central component of the chromatin modifier complex NSL, whose loss in hepatocytes leads to cirrhosis development.
Publications
SELECT dxsjj_posts.*
FROM dxsjj_posts LEFT JOIN dxsjj_postmeta ON ( dxsjj_posts.ID = dxsjj_postmeta.post_id ) LEFT JOIN dxsjj_postmeta AS mt1 ON ( dxsjj_posts.ID = mt1.post_id AND mt1.meta_key = 'factor_impacto' ) LEFT JOIN dxsjj_postmeta AS mt2 ON ( dxsjj_posts.ID = mt2.post_id ) LEFT JOIN dxsjj_postmeta AS mt3 ON ( dxsjj_posts.ID = mt3.post_id ) LEFT JOIN dxsjj_postmeta AS mt4 ON ( dxsjj_posts.ID = mt4.post_id )
WHERE 1=1 AND (
(
dxsjj_postmeta.meta_key = 'factor_impacto'
OR
mt1.post_id IS NULL
)
AND
mt2.meta_key = 'autores'
AND
( mt3.meta_key = 'id_grupos' AND mt3.meta_value LIKE '{1bd0390eaa57efd20f1afb9948d4b8796859987aa59daececac06a9289326d6d}50007756{1bd0390eaa57efd20f1afb9948d4b8796859987aa59daececac06a9289326d6d}' )
AND
( mt4.meta_key = 'anyo' AND CAST(mt4.meta_value AS SIGNED) >= '2018' )
) AND dxsjj_posts.post_type = 'cnio_publication' AND ((dxsjj_posts.post_status = 'publish'))
GROUP BY dxsjj_posts.ID
ORDER BY CAST(mt4.meta_value AS SIGNED) DESC, CAST(dxsjj_postmeta.meta_value AS SIGNED) DESC, CAST(mt2.meta_value AS CHAR) ASC
Pfister D, Núñez NG, Pinyol R, Govaere O, Pinter M, Szydlowska M, Gupta R, Qiu M, Deczkowska A, Weiner A, Müller F, Sinha A, Friebel E, Engleitner T, Lenggenhager D, Moncsek A, Heide D, Stirm K, Kosla J, Kotsiliti E, Leone V, Dudek M, Yousuf S, Inverso D, Singh I, Teijeiro A, Castet F, Montironi C, Haber PK, Tiniakos D, Bedossa P, Cockell S, Younes R, Vacca M, Marra F, Schattenberg JM, Allison M, Bugianesi E, Ratziu V, Pressiani T, D'Alessio A, Personeni N, Rimassa L, Daly AK, Scheiner B, Pomej K, Kirstein MM, Vogel A, Peck-Radosavljevic M, Hucke F, Finkelmeier F, Waidmann O, Trojan J, Schulze K, Wege H, Koch S, Weinmann A, Bueter M, Rössler F, Siebenhüner A, De Dosso S, Mallm JP, Umansky V, Jugold M, Luedde T, Schietinger A, Schirmacher P, Emu B, Augustin HG, Billeter A, Müller-Stich B, Kikuchi H, Duda DG, Kütting F, Waldschmidt DT, Ebert MP, Rahbari N, Mei HE, Schulz AR, Ringelhan M, Malek N, Spahn S, Bitzer M, Ruiz de Galarreta M, Lujambio A, Dufour JF, Marron TU, Kaseb A, Kudo M, Huang YH, Djouder N, Wolter K, Zender L, Marche PN, Decaens T, Pinato DJ, Rad R, Mertens JC, Weber A, Unger K, Meissner F, Roth S, Jilkova ZM, Claassen M, Anstee QM, Amit I, Knolle P, Becher B, Llovet JM, Heikenwalder M (2021).NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature 592, 450-456. CNIO Publication.
Malehmir M, Pfister D, Gallage S, Szydlowska M, Inverso D, Kotsiliti E, Leone V, Peiseler M, Surewaard BGJ, Rath D, Ali A, Wolf MJ, Drescher H, Healy ME, Dauch D, Kroy D, Krenkel O, Kohlhepp M, Engleitner T, Olkus A, Sijmonsma T, Volz J, Deppermann C, Stegner D, Helbling P, Nombela-Arrieta C, Rafiei A, Hinterleitner M, Rall M, Baku F, Borst O, Wilson CL, Leslie J, O'Connor T, Weston CJ, Adams DH, Sheriff L, Teijeiro A, Prinz M, Bogeska R, Anstee N, Bongers MN, Notohamiprodjo M, Geisler T, Withers DJ, Ware J, Mann DA, Augustin HG, Vegiopoulos A, Milsom MD, Rose AJ, Lalor PF, Llovet JM, Pinyol R, Tacke F, Rad R, Matter M, Djouder N, Kubes P, Knolle PA, Unger K, Zender L, Nieswandt B, Gawaz M, Weber A, Heikenwalder M (2019).Platelet GPIba is a mediator and potential interventional target for NASH and subsequent liver cancer. Nat Med 25, 641-655. CNIO Publication.
This website uses cookies so that we can provide you with the best user experience possible. Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful.
Strictly Necessary Cookies
Strictly Necessary Cookie should be enabled at all times so that we can save your preferences for cookie settings.
If you disable this cookie, we will not be able to save your preferences. This means that every time you visit this website you will need to enable or disable cookies again.
3rd Party Cookies
This website uses Google Analytics to collect anonymous information such as the number of visitors to the site, and the most popular pages.
Keeping this cookie enabled helps us to improve our website.
Please enable Strictly Necessary Cookies first so that we can save your preferences!
Additional Cookies
This website uses the following additional cookies:
(List the cookies that you are using on the website here.)
Please enable Strictly Necessary Cookies first so that we can save your preferences!