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Investigación
Unidad de Epigenética y Regulación Génica
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Contenidos con Investigacion .
Unidad de Epigenética y Regulación Génica
Regulación epigenética de la identidad el músculo estriado y su implicación en enfermedades raras del tipo de las miopatías idiopáticas y problemas de conducción cardiaca, tales como la fibrilación atrial y el bloqueo atrioventricular. Ensayos Funcionales de Nuevas Mutaciones en Enfermos no Diagnosticados.
Proyecto PID2020-114773GB-I00 (AEI/10.13039/501100011033) financiado por:
Publicaciones destacadas
A partial form of inherited human USP18 deficiency underlies infection and inflammation
Martin-Fernandez, M., Buta, S., Le Voyer, T., Li, Z., Dynesen, L.T., Vuillier, F., Franklin, L., Ailal, F., Muglia Amancio, A., Malle, L., et al. (2022). A partial form of inherited human USP18 deficiency underlies infection and inflammation. Journal of Experimental Medicine 219, e20211273.
PUBMED DOIExcessive negative regulation of type I interferon disrupts viral control in individuals with Down syndrome
Malle, L., Martin-Fernandez, M., Buta, S., Richardson, A., Bush, D., and Bogunovic, D. (2022). Excessive negative regulation of type I interferon disrupts viral control in individuals with Down syndrome. Immunity 55, 2074-2084.e5.
PUBMED DOIHuman IL-23 is essential for IFN-γ–dependent immunity to mycobacteria
Philippot, Q., Ogishi, M., Bohlen, J., Puchan, J., Arias, A.A., Nguyen, T., Martin-Fernandez, M., Conil, C., Rinchai, D., Momenilandi, M., et al. (2023). Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria. Sci. Immunol. 8, eabq5204.
PUBMED DOIAutoimmunity in Down’s syndrome via cytokines, CD4 T cells and CD11c+ B cells
Malle, L., Patel, R.S., Martin-Fernandez, M., Stewart, O.J., Philippot, Q., Buta, S., Richardson, A., Barcessat, V., Taft, J., Bastard, P., et al. (2023). Autoimmunity in Down’s syndrome via cytokines, CD4 T cells and CD11c+ B cells. Nature 615, 305–314.
PUBMED DOIIndividuals with JAK1 variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis
Horesh, M.E., Martin-Fernandez, M., Gruber, C., Buta, S., Le Voyer, T., Puzenat, E., Lesmana, H., Wu, Y., Richardson, A., Stein, D., et al. (2024). Individuals with JAK1 variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis. Journal of Experimental Medicine 221, e20232387.
PUBMED DOIHomozygous STAT2 gain-of-function mutation by loss of USP18 activity in a patient with type I interferonopathy
Gruber, C., Martin-Fernandez, M., Ailal, F., Qiu, X., Taft, J., Altman, J., Rosain, J., Buta, S., Bousfiha, A., Casanova, J.-L., et al. (2020). Homozygous STAT2 gain-of-function mutation by loss of USP18 activity in a patient with type I interferonopathy. Journal of Experimental Medicine 217, e20192319.
PUBMED DOIJAK Inhibitor Therapy in a Child with Inherited USP18 Deficiency
Alsohime, F., Martin-Fernandez, M., Temsah, M.-H., Alabdulhafid, M., Le Voyer, T., Alghamdi, M., Qiu, X., Alotaibi, N., Alkahtani, A., Buta, S., et al. (2020). JAK Inhibitor Therapy in a Child with Inherited USP18 Deficiency. N Engl J Med 382, 256–265.
PUBMED DOIISG15 protects human Tregs from interferon alpha‐induced contraction in a cell‐intrinsic fashion
Pacella, I., Spinelli, F.R., Severa, M., Timperi, E., Tucci, G., Zagaglioni, M., Ceccarelli, F., Rizzo, F., Coccia, E.M., Patel, R.S., et al. (2020). ISG15 protects human Tregs from interferon alpha‐induced contraction in a cell‐intrinsic fashion. Clin & Trans Imm 9, e1221.
PUBMED DOIThe Usefulness of Bone Biomarkers for Monitoring Treatment Disease: A Comparative Study in Osteolytic and Osteosclerotic Bone Metastasis Models
Martín-Fernández, M., Valencia, K., Zandueta, C., Ormazábal, C., Martínez-Canarias, S., Lecanda, F., and De La Piedra, C. (2017). The Usefulness of Bone Biomarkers for Monitoring Treatment Disease: A Comparative Study in Osteolytic and Osteosclerotic Bone Metastasis Models. Translational Oncology 10, 255–261.
PUBMED DOIHuman USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome
Meuwissen, M.E.C., Schot, R., Buta, S., Oudesluijs, G., Tinschert, S., Speer, S.D., Li, Z., van Unen, L., Heijsman, D., Goldmann, T., et al. (2016). Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome. Journal of Experimental Medicine 213, 1163–1174.
PUBMED DOIBone turnover markers as predictive indicators of outcome in patients with breast cancer and bone metastases treated with bisphosphonates: Results from a 2-year multicentre observational study (ZOMAR study)
Barnadas, A., Manso, L., De La Piedra, C., Meseguer, C., Crespo, C., Gómez, P., Calvo, L., Martinez, P., Ruiz-Borrego, M., Perelló, A., et al. (2014). Bone turnover markers as predictive indicators of outcome in patients with breast cancer and bone metastases treated with bisphosphonates: Results from a 2-year multicentre observational study (ZOMAR study). Bone 68, 32–40. https://linkinghub.elsevier.com/retrieve/pii/S8756328214002993
DOIEffects of PTH (1–84) on bone quality in a validated model of osteoporosis due to androgenic deprivation.
Martín-Fernández, M., Martínez, E., Díaz-Curiel, M., Guede, D., Caeiro, J.R., and De La Piedra, C. (2014). Effects of PTH (1–84) on bone quality in a validated model of osteoporosis due to androgenic deprivation. The Aging Male 17, 42–50.
PUBMED DOIUsefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study
De La Piedra, C., Alcaraz, A., Bellmunt, J., Meseguer, C., Gómez-Caamano, A., Ribal, M.J., Vázquez, F., Anido, U., Samper, P., Esteban, E., et al. (2013). Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study. Br J Cancer 108, 2565–2572.
PUBMED DOImiR-326 associates with biochemical markers of bone turnover in lung cancer bone metastasis
Valencia, K., Martín-Fernández, M., Zandueta, C., Ormazábal, C., Martínez-Canarias, S., Bandrés, E., De La Piedra, C., and Lecanda, F. (2013). miR-326 associates with biochemical markers of bone turnover in lung cancer bone metastasis. Bone 52, 532–539.
PUBMED DOIPro-tumoral Ca2+ signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma.
Pro-tumoral Ca2+ signaling is dependent on Slowpoke and Ca-α1T channels in Drosophila melanogaster glioma.Alza L, Montes-Labrador P, Megías D, Casali A, Casas-Tintó S, Herreros J, Cantí C. Sci Rep. 2026 Mar 6;16(1):12297
PUBMED DOIProtective effects of crocin-enriched tomato in ageing and brain mitochondrial function using Drosophila melanogaster. García-Ricote I, Jiménez AJL, Megías D, Gavira-O Neill CE, Gómez-Gómez L, Ahrazem O, Casas-Tintó S. Biomed Pharmacother. 2026 Mar;196:119119. doi: 10.1016/j.biopha.2026.119119. Epub 2026 Feb 12. PMID: 41687549
Protective effects of crocin-enriched tomato in ageing and brain mitochondrial function using Drosophila melanogaster. García-Ricote I, Jiménez AJL, Megías D, Gavira-O Neill CE, Gómez-Gómez L, Ahrazem O, Casas-Tintó S. Biomed Pharmacother. 2026 Mar;196:119119. Epub 2026 Feb 12.
PUBMED DOIMultifunctional biofunctionalized hybrid nanoantifungals with novel active coating agents based on cinnamaldehyde- and β-cyclocitral-modified polydopamine
Multifunctional biofunctionalized hybrid nanoantifungals with novel active coating agents based on cinnamaldehyde- and β-cyclocitral-modified polydopamine. García-Simarro MP, Mondéjar-López M, García-Martínez JC, Cuesta-Casas A, Casas-Tintó S, Ahrazem O, Gómez-Gómez L, Niza E. Mater Today Bio. 2025 Dec 10;36:102645. eCollection 2026 Feb.
PUBMED DOIAdult central nervous regeneration in Drosophila : Evidence for glial lineage conversion and neurogenic potential post-injury
Adult central nervous regeneration in Drosophila : Evidence for glial lineage conversion and neurogenic potential post-injury. Casas-Tintó S, Losada-Pérez M. Neural Regen Res. 2026 Jul 1;21(7):2948-2949. Epub 2025 Nov 25.
PUBMED DOIInformación adicional
Nuestro principal objetivo es estudiar los mecanismos epigenéticos que regulan la fisiología y la patofisiología del músculo estriado, centrándonos en el complejo remodelador de la cromatina Chd4/NURD. Hemos demostrado que Chd4/NURD controla la identidad de ambos músculos estriados ya que, en el corazón, mantiene reprimidos los genes sarcoméricos del músculo esquelético y viceversa. Actualmente, hemos enfocado nuestro estudio en las proteínas que interaccionan con la ADN-helicasa Chd4, componente principal del complejo NuRD, para intentar comprender cómo influyen estas proteínas en el reclutamiento y función del complejo Chd4/NuRD, y su impacto en la expresión génica que determina la identidad del músculo estriado.
Por otra parte, estamos también estudiando el papel de la helicasa de ADN y RNA llamada Rhau en el desarrollo cardiaco y su impacto en el funcionamiento del sistema de conducción cardiaco. Nuestra metodología de trabajo incluye tanto abordajes in vivo, con el uso de ratones modificados genéticamente, como abordajes in vitro. Con todo, intentamos entender los mecanismos por los cuáles se desarrolla la identidad del músculo estriado para comprender las bases moleculares de algunas patologías raras asociadas a este tejido, tales como algunas miopatías y determinados problemas de conducción cardiaca para, con ello, desarrollar terapias para estas enfermedades.