Cell migration and epigenetics

Nuclear changes induced by cell-matrix interactions

RESEARCH BACKGROUND

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.

EVENTS AND NEWS

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, click here for more information.

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

RESEARCH GROUP

Ms. Elena Madrazo (PhD student)

Ms. Estefanía Alonso (PhD student)

Mr. David Acitores (Master student)

Ms. Laura Dalia (Undergraduate student)

WORKING WITH US

We are always interested in recruiting talented and motivated people with a strong interest in immunology, leukemia and cell migration fields.

RECENT KEY PUBLICATIONS

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 Jul 9. pii: 201719405.

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.

Redondo-Muñoz J, Pérez-García V, Rodríguez MJ, Valpuesta JM, Carrera AC.Phosphoinositide 3-kinase beta protects nuclear envelope integrity by controlling RCC1 localization and Ran activity. Mol Cell Biol.2015 35:249-63.

Redondo-Muñoz J, Rodríguez MJ, Silió V, Pérez-García V, Valpuesta JM, Carrera AC.Phosphoinositide 3-kinase beta controls replication factor C assembly and function. Nucleic Acids Res. 2013 41:855-68.

García-Bernal D, Redondo-Muñoz J, Dios-Esponera A, Chèvre R, Bailón E, Garayoa M, Arellano-Sánchez N, Gutierrez NC, Hidalgo A, García-Pardo A, Teixidó J.Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function. J Pathol. 2013 229:36-48