Forschungsgruppe Prof. Dr. Henner Farin
Experimentelle Modelle für die Mikroumgebung beim Darmkrebs
Unsere Arbeitsgruppe erforscht die zellulären und molekularen Vorgänge bei der Entstehung von Darmkrebs. Insbesondere interessiert uns die Kommunikation verschiedener Zelltypen in der unmittelbaren Umgebung des Tumors, dem sogenannten „Tumor-Microenvironment”. Dabei nutzen wir „Organoide“, ein neuartiges dreidimensionales Gewebekultur-System.
Das Kolorektale Karzinom (CRC) ist eine der häufigsten krebsbedingten Todesursachen. Es ist durch zahlreiche genetische und epigenetische Veränderungen gekennzeichnet. Der individuelle Tumorphänotyp wird stark von der Mikroumgebung des Tumors beeinflusst, zu der Fibroblasten, Gefäße und Immunzellen gehören. Um diese komplexe Krankheit zu untersuchen und personalisierte therapeutische Strategien zu entwickeln, ist ein umfassender Ansatz erforderlich.
Vom Patienten stammende Tumororganoide und Ko-Kulturmodelle
Patienten-abgeleitete Organoide (PDOs) haben sich als Forschungsmodell etabliert, das die 3D-Organisation des gastrointestinalen Epithels nachahmt. Darüber hinaus können Ko-Kulturen mit Stromazellen durchgeführt werden, um ein gewebeähnliches Umfeld zu simulieren. Mittels PDOs können „lebende Biobanken“ aufgebaut und kryokonserviert werden, welche die Tumor-Heterogenität zwischen Patienten repräsentieren. In Zusammenarbeit mit dem Universitären Tumorzentrum Frankfurt und mit Unterstützung des Frankfurt Cancer Institute (FCI) betreiben wir die FCI Organoid Biobank, um die Kultur und Analyse von PDOs zu unterstützen.
Genetische Regulatoren der CRC-Mikroumgebung
Die Homöostase des Gewebes hängt von der Interaktion der Stammzellen mit Signalen aus der Mikroumgebung ab. In Tumoren ist diese Interaktion gestört, was zu unkontrolliertem Wachstum führt. Zur Untersuchung der Kommunikation zwischen den unterschiedlichen Zelltypen im CRC verwenden wir Organoid Ko-Kulturen und Transplantationsmodelle. Kürzlich haben wir festgestellt, dass Mutationen, welche die Wnt-Signalübertragung aktivieren, auch die krebsassoziierten Fibroblasten (CAFs) beeinflussen. Die Hemmung des Wnt-Signals führt dabei zu einem CAF-Subtyp, der Tumorzellen invasiver macht (Mosa et al., Cancer Research 2020), was zeigt, wie die Plastizität von Stromazellen die malignen Eigenschaften von Tumoren regulieren kann.
Um die Einflüsse der Tumormikroumgebung auf einer umfassenden Ebene zu untersuchen, haben wir mit Hilfe der CRISPR/Cas9-Technologie genetische Screens in menschlichen Darmorganoiden durchgeführt. Dies ermöglicht die unvoreingenommene Identifizierung von Tumorsuppressorgenen, die das Wachstum in vitro und nach Xenotransplantation fördern (Michels et al., Cell Stem Cell 2020). In Kombination mit PDOs könnte diese Plattform auch dazu beitragen, individuelle therapeutische Ziele für das kolorektale Karzinom zu entschlüsseln.
Personalisierte Modelle für CRC-Therapie und pharmakogenomisches Screening
PDOs können als präklinisches Modell dienen, um therapeutische Strategien zu identifizieren. In Zusammenarbeit mit Prof. Wels (Georg-Speyer-Haus) haben wir mit chimären Antigenrezeptoren (CAR) modifizierte NK-Zellen verwendet, um die Zytotoxizität gegen Darmkrebszellen zu induzieren. Dazu haben wir enzymatische und Lebendzell-Mikroskopie entwickelt, um die Wirksamkeit der CAR-Zellen zu untersuchen (Schnalzger et al., EMBO Journal 2019).
Als Teilnehmer des EU-Konsortiums „EUbOPEN“ (Enabling and unlocking biology in the OPEN, 2020-2024) haben wir eine PDO-Wirkstoffscreening-Plattform entwickelt. Das EUbOPEN-Konsortium wird von der „Innovative Medicines Initiative“ (IMI2) finanziert und zielt darauf ab, eine frei zugängliche chemogenomische Bibliothek von Wirkstoffen zu erstellen, die humane Genome möglichst umfassend abdeckt. Gemeinsam mit unseren Partnern aus dem akademischen Bereich und der pharmazeutischen Industrie entwickeln wir sog. „Human Tissue Assays“ für CRC. Wir führen pharmakologische Hochdurchsatz-Screens an PDO-Biobanken durch, um Resistenzmechanismen und therapeutische Strategien zu identifizieren.
Das EUbOPEN-Projekt wurde vom „Joint Undertaking Innovative Medicines Initiative 2“ unter der Finanzhilfevereinbarung Nr. 875510 gefördert. Dieses „Joint Undertaking“ wird durch das Forschungs- und Innovationsprogramm Horizont 2020 der Europäischen Union, EFPIA-Unternehmen und assoziierte Partner unterstützt: KTH, OICR, Diamond und McGill. Dieser Bericht gibt die Ansichten der Autoren wieder. Weder die IMI noch die Europäische Union, EFPIA oder ein assoziierter Partner haften für die Verwendung der hierin enthaltenen Informationen.
Team
Ausgewählte Publikationen
Schnalzger TE, de Groot MHP, Zhang C, Mosa MH, Michels BE, Röder J, Darvishi T, Wels WS, Farin HF. (2019)
3D model for CAR-mediated cytotoxicity using patient-derived colorectal cancer organoids.
The EMBO Journal. 38(12):e100928.
Michels BE, Mosa MH, Streibl BI, Zhan T, Menche C, Abou-El-Ardat K, Darvishi T, Członka E, Wagner S, Winter J, Medyouf H. Boutros M, Farin HF. (2020)
Pooled In Vitro and In Vivo CRISPR-Cas9 Screening Identifies Tumor Suppressors in Human Colon Organoids.
Cell Stem Cell. 26: 782-792.e7.
Farin HF*, Mosa MH, Ndreshkjana B, Grebbin BM, Ritter B, Menche C, Kennel KB, Ziegler PK, Szabo L, Bollrath J, Rieder D, Michels BE, Kress A, Bozlar M, Darvishi T, Stier S, Kur I-M, Bankov K, Kesselring R, Fichtner-Feigl S, Brune B, Goetze TO, Al-Batran S-E, Brandts CH, Bechstein WO, Wild PJ, Weigert A, Muller S, Knapp S, Trajanoski Z, Greten FR*. (2023)
Colorectal cancer organoid-stroma biobank allows subtype-specific assessment of individualized therapy responses.
Cancer Discovery. 13(10):2192–2211. * corresponding authors
Menche C*, Schuhwerk H*, Armstark I, Gupta P, Fuchs K, van Roey R, Mosa MH, Hartebrodt A, Hajjaj Y, Clavel Ezquerra A, Selvaraju MK, Geppert CI, Bärthel S, Saur D, Greten FR, Brabletz S, Blumenthal DB, Weigert A, Brabletz T**, Farin HF**, Stemmler MP**. (2024)
ZEB1-mediated fibroblast polarization controls inflammation and sensitivity to immunotherapy in colorectal cancer.
EMBO reports. 25(8):3406–3431. * first authors ** corresponding authors
Issing C*, Menche C, Richter MR, Mosa MH, von der Grün J, Fleischmann M, Thoenissen P, Winkelmann R, Darvishi T, Loth AG, Ghanaati S, Rödel F, Wild PJ, Brandts CH, Stöver T, Farin HF*. (2025)
Head and neck tumor organoid biobank for modelling individual responses to radiation therapy according to the TP53/HPV status.
J Exp Clin Cancer Res. 2025 Mar 5;44(1):85. doi: 10.1186/s13046-025-03345-3.
PMID: 40045309 Free PMC article. * corresponding authors
Weitere Publikationen
Synergistic targeting of cancer cells through simultaneous inhibition of key metabolic enzymes
Cell Death Differ. 2025 Dec;32(12):2239-2256. doi: 10.1038/s41418-025-01532-5. Epub 2025 Jun 23.
ABSTRACT
As cancer cell specific rewiring of metabolic networks creates…
Head and neck tumor organoid biobank for modelling individual responses to radiation therapy according to the TP53/HPV status
J Exp Clin Cancer Res. 2025 Mar 5;44(1):85. doi: 10.1186/s13046-025-03345-3.
ABSTRACT
BACKGROUND: Head and neck cancers (HNC) represent an extremely heterogeneous group…
Author Correction: Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways
Nat Commun. 2024 Dec 19;15(1):10698. doi: 10.1038/s41467-024-55044-w.
NO ABSTRACT
PMID:39702301 | PMC:PMC11659427 | DOI:10.1038/s41467-024-55044-w
Toward target 2035: EUbOPEN - a public-private partnership to enable & unlock biology in the open
RSC Med Chem. 2024 Nov 29;16(2):457-464. doi: 10.1039/d4md00735b. eCollection 2025 Feb 19.
ABSTRACT
Target 2035 is a global initiative that seeks to identify a…
Establishment of Patient-Derived Organoids from Colorectal Cancer Resection Samples
Methods Mol Biol. 2025;2951:245-255. doi: 10.1007/7651_2024_575.
ABSTRACT
Colorectal cancer (CRC) organoids can serve as powerful preclinical cell models that accurately…
ZEB1-mediated fibroblast polarization controls inflammation and sensitivity to immunotherapy in colorectal cancer
EMBO Rep. 2024 Aug;25(8):3406-3431. doi: 10.1038/s44319-024-00186-7. Epub 2024 Jun 27.
ABSTRACT
The EMT-transcription factor ZEB1 is heterogeneously expressed in tumor…
Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways
Nat Commun. 2024 May 15;15(1):4096. doi: 10.1038/s41467-024-48422-x.
ABSTRACT
The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to…
Downregulation of V-ATPase V0 Sector Induces Microvillus Atrophy Independently of Apical Trafficking in the Mammalian Intestine
Cell Mol Gastroenterol Hepatol. 2024;17(6):1072-1075. doi: 10.1016/j.jcmgh.2024.02.011. Epub 2024 Feb 16.
NO ABSTRACT
PMID:38369130 | PMC:PMC11127621 | DOI:10.1016/j.jcmgh.2024.02.011
Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer
iScience. 2023 Nov 4;26(12):108399. doi: 10.1016/j.isci.2023.108399. eCollection 2023 Dec 15.
ABSTRACT
Precision oncology approaches for patients with colorectal cancer…
Colorectal Cancer Organoid-Stroma Biobank Allows Subtype-Specific Assessment of Individualized Therapy Responses
Cancer Discov. 2023 Oct 5;13(10):2192-2211. doi: 10.1158/2159-8290.CD-23-0050.
ABSTRACT
In colorectal cancers, the tumor microenvironment plays a key role in prognosis…
Actin dynamics regulation by TTC7A/PI4KIIIα limits DNA damage and cell death under confinement
J Allergy Clin Immunol. 2023 Oct;152(4):949-960. doi: 10.1016/j.jaci.2023.06.016. Epub 2023 Jun 29.
ABSTRACT
BACKGROUND: The actin cytoskeleton has a crucial role in the…
Deep Annotation of Donated Chemical Probes (DCP) in Organotypic Human Liver Cultures and Patient-Derived Organoids from Tumor and Normal Colorectum
ACS Chem Biol. 2023 Apr 21;18(4):822-836. doi: 10.1021/acschembio.2c00877. Epub 2023 Mar 21.
ABSTRACT
Well-characterized small molecules are essential tools for studying…
Synthetic enforcement of STING signaling in cancer cells appropriates the immune microenvironment for checkpoint inhibitor therapy
Sci Adv. 2023 Mar 17;9(11):eadd8564. doi: 10.1126/sciadv.add8564. Epub 2023 Mar 15.
ABSTRACT
Immune checkpoint inhibitors (ICIs) enhance anticancer immunity by releasing…
Immune escape of colorectal tumours via local LRH-1/Cyp11b1-mediated synthesis of immunosuppressive glucocorticoids
Mol Oncol. 2023 Aug;17(8):1545-1566. doi: 10.1002/1878-0261.13414. Epub 2023 Mar 9.
ABSTRACT
Control of tumour development and growth by the immune system critically…
Loss of SUV420H2-Dependent Chromatin Compaction Drives Right-Sided Colon Cancer Progression
Gastroenterology. 2023 Feb;164(2):214-227. doi: 10.1053/j.gastro.2022.10.036. Epub 2022 Nov 17.
ABSTRACT
BACKGROUND & AIMS: Epigenetic processes regulating gene…
Expansion of T memory stem cells with superior anti-tumor immunity by Urolithin A-induced mitophagy
Immunity. 2022 Nov 8;55(11):2059-2073.e8. doi: 10.1016/j.immuni.2022.09.014. Epub 2022 Oct 19.
ABSTRACT
T memory stem cells (TSCM) display increased self-renewal and…
Strategies for genetic manipulation of adult stem cell-derived organoids
Exp Mol Med. 2021 Oct;53(10):1483-1494. doi: 10.1038/s12276-021-00609-8. Epub 2021 Oct 18.
ABSTRACT
Organoid technology allows the expansion of primary epithelial cells…
A Wnt-Induced Phenotypic Switch in Cancer-Associated Fibroblasts Inhibits EMT in Colorectal Cancer
Cancer Res. 2020 Dec 15;80(24):5569-5582. doi: 10.1158/0008-5472.CAN-20-0263. Epub 2020 Oct 14.
ABSTRACT
Tumor progression is recognized as a result of an evolving…
AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer
J Exp Med. 2020 Oct 5;217(10):e20191515. doi: 10.1084/jem.20191515.
ABSTRACT
Recently, a transcriptome-based consensus molecular subtype (CMS) classification of…
Cellular and Molecular Changes of Brain Metastases-Associated Myeloid Cells during Disease Progression and Therapeutic Response
iScience. 2020 Jun 26;23(6):101178. doi: 10.1016/j.isci.2020.101178. Epub 2020 May 18.
ABSTRACT
Brain-resident microglia and bone marrow-derived macrophages represent…
Pooled In Vitro and In Vivo CRISPR-Cas9 Screening Identifies Tumor Suppressors in Human Colon Organoids
Cell Stem Cell. 2020 May 7;26(5):782-792.e7. doi: 10.1016/j.stem.2020.04.003. Epub 2020 Apr 28.
ABSTRACT
Colorectal cancer (CRC) is characterized by prominent genetic…
Conformation-specific inhibitors of activated Ras GTPases reveal limited Ras dependency of patient-derived cancer organoids
J Biol Chem. 2020 Apr 3;295(14):4526-4540. doi: 10.1074/jbc.RA119.011025. Epub 2020 Feb 20.
ABSTRACT
The small GTPases H, K, and NRAS are molecular switches…
STAT3 activation through IL-6/IL-11 in cancer-associated fibroblasts promotes colorectal tumour development and correlates with poor prognosis
Gut. 2020 Jul;69(7):1269-1282. doi: 10.1136/gutjnl-2019-319200. Epub 2019 Nov 4.
ABSTRACT
OBJECTIVE: Cancer-associated fibroblasts (CAFs) influence the tumour…
3D model for CAR-mediated cytotoxicity using patient-derived colorectal cancer organoids
EMBO J. 2019 Jun 17;38(12):e100928. doi: 10.15252/embj.2018100928. Epub 2019 Apr 29.
ABSTRACT
Immunotherapy using chimeric antigen receptor (CAR)-engineered lymphocytes…
Cancer-induced inflammation and inflammation-induced cancer in colon: a role for S1P lyase
Oncogene. 2019 Jun;38(24):4788-4803. doi: 10.1038/s41388-019-0758-x. Epub 2019 Feb 28.
ABSTRACT
A role of sphingolipids for inflammatory bowel disease and cancer is…
Human colon organoids reveal distinct physiologic and oncogenic Wnt responses
J Exp Med. 2019 Mar 4;216(3):704-720. doi: 10.1084/jem.20180823. Epub 2019 Feb 21.
ABSTRACT
Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as…
The transcriptional regulator FUBP1 influences disease outcome in murine and human myeloid leukemia
Leukemia. 2019 Jul;33(7):1700-1712. doi: 10.1038/s41375-018-0358-8. Epub 2019 Jan 11.
ABSTRACT
The transcriptional regulator far upstream element binding protein 1…
Dynamic Formation of Microvillus Inclusions During Enterocyte Differentiation in Munc18-2-Deficient Intestinal Organoids
Cell Mol Gastroenterol Hepatol. 2018 Aug 14;6(4):477-493.e1. doi: 10.1016/j.jcmgh.2018.08.001. eCollection 2018.
ABSTRACT
BACKGROUND & AIMS: Microvillus inclusion…
Intestinal Inflammation and Dysregulated Immunity in Patients With Inherited Caspase-8 Deficiency
Gastroenterology. 2019 Jan;156(1):275-278. doi: 10.1053/j.gastro.2018.09.041. Epub 2018 Sep 26.
NO ABSTRACT
PMID:30267714 | DOI:10.1053/j.gastro.2018.09.041
YAP-IL-6ST autoregulatory loop activated on APC loss controls colonic tumorigenesis
Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1643-1648. doi: 10.1073/pnas.1620290114. Epub 2017 Jan 27.
ABSTRACT
Loss of tumor suppressor adenomatous polyposis coli…
Tbx2 and Tbx3 Act Downstream of Shh to Maintain Canonical Wnt Signaling during Branching Morphogenesis of the Murine Lung
Dev Cell. 2016 Oct 24;39(2):239-253. doi: 10.1016/j.devcel.2016.08.007. Epub 2016 Oct 6.
ABSTRACT
Numerous signals drive the proliferative expansion of the distal…
Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research
Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11859-11864. doi: 10.1073/pnas.1614057113. Epub 2016 Oct 5.
ABSTRACT
Current mouse models for colorectal cancer often…
Lack of Genetic Interaction between Tbx18 and Tbx2/Tbx20 in Mouse Epicardial Development
PLoS One. 2016 Jun 2;11(6):e0156787. doi: 10.1371/journal.pone.0156787. eCollection 2016.
ABSTRACT
The epicardium, the outermost layer of the heart, is an essential…
Misexpression of Tbx18 in cardiac chambers of fetal mice interferes with chamber-specific developmental programs but does not induce a pacemaker-like gene signature
J Mol Cell Cardiol. 2016 Aug;97:140-9. doi: 10.1016/j.yjmcc.2016.05.004. Epub 2016 May 11.
ABSTRACT
Initiation of cardiac excitation depends on a specialized group of…
Visualization of a short-range Wnt gradient in the intestinal stem-cell niche
Nature. 2016 Feb 18;530(7590):340-3. doi: 10.1038/nature16937. Epub 2016 Feb 10.
ABSTRACT
Mammalian Wnt proteins are believed to act as short-range signals, yet have not…
Replacement of Lost Lgr5-Positive Stem Cells through Plasticity of Their Enterocyte-Lineage Daughters
Cell Stem Cell. 2016 Feb 4;18(2):203-13. doi: 10.1016/j.stem.2016.01.001. Epub 2016 Jan 28.
ABSTRACT
Intestinal crypts display robust regeneration upon injury. The…
Germline deletions in the tumour suppressor gene FOCAD are associated with polyposis and colorectal cancer development
J Pathol. 2015 Jun;236(2):155-64. doi: 10.1002/path.4520. Epub 2015 Mar 26.
ABSTRACT
Heritable genetic variants can significantly affect the lifetime risk of developing…
Plasticity within stem cell hierarchies in mammalian epithelia
Trends Cell Biol. 2015 Feb;25(2):100-8. doi: 10.1016/j.tcb.2014.09.003. Epub 2014 Oct 9.
ABSTRACT
Tissue homeostasis and regeneration are fueled by resident stem cells…
Immune deficiency-related enteropathy-lymphocytopenia-alopecia syndrome results from tetratricopeptide repeat domain 7A deficiency
J Allergy Clin Immunol. 2014 Dec;134(6):1354-1364.e6. doi: 10.1016/j.jaci.2014.07.019. Epub 2014 Aug 28.
ABSTRACT
BACKGROUND: Inflammatory bowel disease (IBD) is one of…
TTC7A, a critical effector for the intestinal and immune system homeostasis
Med Sci (Paris). 2014 Jun-Jul;30(6-7):616-8. doi: 10.1051/medsci/20143006006. Epub 2014 Jul 11.
NO ABSTRACT
PMID:25014447 | DOI:10.1051/medsci/20143006006
Paneth cell extrusion and release of antimicrobial products is directly controlled by immune cell-derived IFN-γ
J Exp Med. 2014 Jun 30;211(7):1393-405. doi: 10.1084/jem.20130753.
ABSTRACT
Paneth cells (PCs) are terminally differentiated, highly specialized secretory cells located…
Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells
Stem Cell Reports. 2014 Jun 3;2(6):838-52. doi: 10.1016/j.stemcr.2014.05.001. eCollection 2014 Jun 3.
ABSTRACT
Genetically engineered human pluripotent stem cells…
Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny
Nat Methods. 2014 Jan;11(1):106-12. doi: 10.1038/nmeth.2737. Epub 2013 Dec 1.
ABSTRACT
Although Lgr5(+) intestinal stem cells have been expanded in vitro as organoids,…
TTC7A mutations disrupt intestinal epithelial apicobasal polarity
J Clin Invest. 2014 Jan;124(1):328-37. doi: 10.1172/JCI71471.
ABSTRACT
Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes…
Generation of L cells in mouse and human small intestine organoids
Diabetes. 2014 Feb;63(2):410-20. doi: 10.2337/db13-0991. Epub 2013 Oct 15.
ABSTRACT
Upon a nutrient challenge, L cells produce glucagon-like peptide 1 (GLP-1), a…
Retromer dependent recycling of the Wnt secretion factor Wls is dispensable for stem cell maintenance in the mammalian intestinal epithelium
PLoS One. 2013 Oct 9;8(10):e76971. doi: 10.1371/journal.pone.0076971. eCollection 2013.
ABSTRACT
In C. elegans and Drosophila, retromer mediated retrograde transport of…
Tbx2 terminates shh/fgf signaling in the developing mouse limb bud by direct repression of gremlin1
PLoS Genet. 2013;9(4):e1003467. doi: 10.1371/journal.pgen.1003467. Epub 2013 Apr 25.
ABSTRACT
Vertebrate limb outgrowth is driven by a positive feedback loop that…
Tbx2 controls lung growth by direct repression of the cell cycle inhibitor genes Cdkn1a and Cdkn1b
PLoS Genet. 2013;9(1):e1003189. doi: 10.1371/journal.pgen.1003189. Epub 2013 Jan 17.
ABSTRACT
Vertebrate organ development relies on the precise spatiotemporal…
Tbx18 function in epicardial development
Cardiovasc Res. 2012 Dec 1;96(3):476-83. doi: 10.1093/cvr/cvs277. Epub 2012 Aug 27.
ABSTRACT
AIMS: The embryonic epicardium is a source of smooth muscle cells and…
Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells
Gastroenterology. 2012 Dec;143(6):1518-1529.e7. doi: 10.1053/j.gastro.2012.08.031. Epub 2012 Aug 23.
ABSTRACT
BACKGROUND & AIMS: Wnt signaling regulates multiple aspects…
Canonical Wnt signaling regulates smooth muscle precursor development in the mouse ureter
Development. 2012 Sep;139(17):3099-108. doi: 10.1242/dev.077388. Epub 2012 Jul 25.
ABSTRACT
Smooth muscle cells (SMCs) are a key component of many visceral organs,…
Controlled gene expression in primary Lgr5 organoid cultures
Nat Methods. 2011 Dec 4;9(1):81-3. doi: 10.1038/nmeth.1802.
ABSTRACT
The study of gene function in endodermal epithelia such as of stomach, small intestine and colon…
Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation
Cell Mol Life Sci. 2012 Apr;69(8):1377-89. doi: 10.1007/s00018-011-0884-2. Epub 2011 Dec 1.
ABSTRACT
A key step in heart development is the coordinated development of…
Hydroureternephrosis due to loss of Sox9-regulated smooth muscle cell differentiation of the ureteric mesenchyme
Hum Mol Genet. 2010 Dec 15;19(24):4918-29. doi: 10.1093/hmg/ddq426. Epub 2010 Sep 29.
ABSTRACT
Congenital ureter anomalies, including hydroureter, affect up to 1% of the…
Tbx20 interacts with smads to confine tbx2 expression to the atrioventricular canal
Circ Res. 2009 Aug 28;105(5):442-52. doi: 10.1161/CIRCRESAHA.109.196063. Epub 2009 Aug 6.
ABSTRACT
RATIONALE: T-box transcription factors play critical roles in the…
TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome
Am J Hum Genet. 2008 Nov;83(5):649-55. doi: 10.1016/j.ajhg.2008.10.011.
ABSTRACT
Members of the evolutionarily conserved T-box family of transcription factors are…
T-box protein Tbx18 interacts with the paired box protein Pax3 in the development of the paraxial mesoderm
J Biol Chem. 2008 Sep 12;283(37):25372-25380. doi: 10.1074/jbc.M802723200. Epub 2008 Jul 21.
ABSTRACT
The compartmentalization of somites along their anterior-posterior…
Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors
J Biol Chem. 2007 Aug 31;282(35):25748-59. doi: 10.1074/jbc.M703724200. Epub 2007 Jun 21.
ABSTRACT
Tbox18 (Tbx18) and Tbox15 (Tbx15) encode a closely related pair of…
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