Cell migration and epigenetics
Nuclear changes induced by cell-matrix interactions
Welcome and thanks for visiting our webpage!
We are a group of scientists interested in understanding how epigenetic changes drive the nuclear deformability, migration and infiltration of leukaemia cells. We are part of the Faculty of Medicine (Complutense University of Madrid, UCM) and the Lydia Becker Institute of Immunology and Inflammation (University of Manchester, UoM).
Cell migration is central to numerous biological functions in embryogenesis, tissue renewal and immunity. Migration of a cell though tissues requires its interaction with its matrix environment, and recently it has become clear that cell plasticity is critical for this motility through narrow spaces. For that, the cell needs to alter the physical properties of the nucleus, as the major and most rigid organelle in the cell body. Most of these advances link the expression of nuclear components, such as lamins, with cell plasticity; however how epigenetic changes affect cell migration is poorly understood. Epigenetic changes control gene transcription and DNA homeostasis, and some of them have been linked to active migration and motility of certain cancer cells.
Lymphocytes, as the immune cells mediating the adaptative response, require fast migration and recycing to/from immune organs to affected tissues, integrin receptors play an essential role during cell migration. Lymphocyte nuclei become remodeled under 2D shear flow conditions, and in a 3D environment when they traverse vessels and migrate through stroma. We hypothesise that both the composition and mechanical properties of the matrix influence migration via a control on cell nuclei. We therefore aim to test this hypothesis by determining how ECM composition and mechanics control nuclear organisation, and how nuclear composition and chromatin modification influence 3D migration. Our work will provide novel insights on how cell-matrix interactions control normal and tumor lymphocyte migration through tissues, which will impact on future treatments for human diseases and cancer.
Ms. Elena Madrazo (PhD student)
Ms. Raquel González Novo (PhD student)
Dr. Héctor Zamora Carreras (Postdoc)
Mr. Ander de Blas (Master student)
Ms. Andrea Cordero (Undergraduate student)
Mr. David Acitores (Master student)
Ms. Laura Dalia (Undergraduate student)
Mr. Celso Yáñez (Master student)
Ms. Estefanía Alonso (PhD student)
Ms. Roberta Turner (Undergraduate student)
Dr. Carmen Mata Martín (Postdoc)
WORKING WITH US
We are always interested in recruiting talented and motivated people with a strong interest in immunology, leukemia and cell migration fields.
EVENTS AND NEWS
Trying to be productive during this difficult time... Delighted to announce that our last paper has been published in Scientific Reports. Great collaboration with Prof. Monroy's group and Dr. Ramírez!
Javier will be preseting our most recent data at the VI WORKSHOP MECHANISMS OF CELL ADHESION, MIGRATION AND INVASION in Badajoz (Spain). See you there!
Our first overseas student Roberta Turner has returned to UK. Thanks to British Society of Haematology for funding her visit.
Our student Celso passed his final TFM.
Raquel González-Novo has joined our lab as a future FPI fellow.
Javier presents this week (27th-30thNovember) our recent publication in the SystemEpgenetics meeting (Amsterdam).
Our students David and Laura have obtained outstanding marks for their final TFM and TGF projects (9.9 and 9.5 respectively).
Dissemination time! Elena is presenting a poster at the Frankfurt Cancer Conference 2018 (Germany) and Javier a poster and short-talk at the 2018 FEBS Advanced Course on the Extracellular Matrix (Greece).
We are extremely honoured to join the new Lydia Becker Institute of Immunology and Inflammation. Please visit https://www.bmh.manchester.ac.uk/research/domains/infection-immunity-inflammation-repair/immunology/ to see more about our new institute and partners.
We are currently organising the 1st Immunology Frontiers Seminar Series-UCM. Please, have a look at: https://www.ucm.es/microbiologia-1/ifss-ucm.
The first English Module within the School of Medicine finished! Such an exciting opportunity to impact on our Master students! See you next academic year.
Our paper published in Scientific Reports (2020). https://www.lavanguardia.com/vida/20200428/48792666080/desarrollan-una-tecnica-para-mejorar-el-diagnostico-de-la-leucemia-aguda.html http://tribuna.ucm.es/43/art4102.php#.Xqaa-ZMzYUs
Interview in Libertad FM (by Antonio Armas). https://www.radioenfermedadesraras.com/podcast/mecanobiologia-del-nucleo-y-migracion-de-celulas-tumorales-contaminacion-exter-ref100078243.html
Javier Redondo-Muñoz Gilead International Scholarship Awardee. http://tribuna.ucm.es/200/art2864.php#.XqacPZMzYUs
Interview in RadioX London (2016). https://sruk.org.uk/es/podcast/episodio-6-adn-epigenetica/
RECENT KEY PUBLICATIONS
Herráez-Aguilar D, Madrazo E, López-Menéndez H, Ramírez M, Monroy F, Redondo-Muñoz J.Multiple particle tracking analysis in isolated nuclei reveals the mechanical phenotype of leukemia cells. Sci Rep. 2020 Apr 21;10(1):6707
Redondo-Muñoz J, García-Pardo A, Teixidó J. Molecular Players in Hematologic Tumor Cell Trafficking. Front Immunol. 2019 Feb 6;10:156.
Dreger M, Madrazo E, Hurlstone A, Redondo-Muñoz J. Novel contribution of epigenetic changes to nuclear dynamics. Nucleus. 2019 Dec;10(1):42-47.
Madrazo E, Ruano D, Abad L, Alonso-Gómez E, Sánchez-Valdepeñas C, González-Murillo Á, Ramírez M, Redondo-Muñoz J. G9a Correlates with VLA-4 Integrin and Influences the Migration of Childhood Acute Lymphoblastic Leukemia Cells. Cancers (Basel). 2018 10(9). pii: E325.
Wang P, Dreger M, Madrazo E, Williams CJ, Samaniego R, Hodson NW, Monroy F, Baena E, Sánchez-Mateos P, Hurlstone A, Redondo-Muñoz J.WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment. Proc Natl Acad Sci U S A. 2018 115:8581-8586.
Madrazo E, Conde AC, Redondo-Muñoz J. Inside the Cell: Integrins as New Governors of Nuclear Alterations? Cancers (Basel). 2017 9: pii: E82.
Zhang X, Cook PC, Zindy E, Williams CJ, Jowitt TA, Streuli CH, MacDonald AS, Redondo-Muñoz J.Integrin α4β1 controls G9a activity that regulates epigenetic changes and nuclear properties required for lymphocyte migration. Nucleic Acids Res. 2016 44:3031-44.
Dr. Adam Hurlstone (The University of Manchester)
Dr. Nigel Hodson (The University of Manchester)
Prof. Chris Pepper (Brighton and Sussex Medical School)
Prof. Francisco Monroy (Complutense University of Madrid)
Dr. Manuel Ramírez Orellana (Hospital Pediátrico Universitario Niño Jesús)
Dr. Paloma Sánchez Mateos (Hospital General Universitario Gregorio Marañón)
Dr. Ronen Alon (Weizmann Institute of Science)