https://www.helenmatthewslab.org/news daily 0.75 2023-07-26 https://www.helenmatthewslab.org/news/td6bppbwsmd6ep60rrigq1hftwthzp monthly 0.5 2023-07-26 https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/58c95019-6a66-417e-bf01-6763459b7c1d/Picture+1.jpg Lab News - Gabija ’s Summer SURE Scheme Project - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://www.helenmatthewslab.org/news/sushilas-preprint-is-online-how-ras-affects-cell-division-orientation monthly 0.5 2023-01-13 https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/2632ea2c-16a2-427f-a4ae-a673e29eae4c/Ras+spindle.jpg Lab News - Sushila’s preprint is online: how Ras affects cell division orientation - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://www.helenmatthewslab.org/news/hamzehs-ug-summer-project monthly 0.5 2022-09-30 https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/3b405b98-83c5-43d1-9083-a6a8d43d6af2/Hamzeh01.jpg Lab News - Hamzeh’s summer project It was a pleasure to host Hamzeh Kanou in the lab for a Generation Research Summer Studentship. Hamzeh is going into his third year of Physics Undergraduate at Sheffield. Hamzeh worked with Professor Buddhapriya Chakrabarti on computational modelling of cell shape transitions. And what better place to start than by looking at some cell shapes down the microscope? Hamzeh tried his hand at tissue culture and microscopy in the lab and turned out to be a natural! Check out his beautiful 3D reconstructions of dividing cells . https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/e43d0e17-5e15-4ca9-bcb8-72339bc7fd53/Hamzeh+series.jpg Lab News - Hamzeh’s summer project - Make it stand out 3D reconstructions of dividing cells (labelled with LiveAct-GFP and imaged using Airyscan confocal microscopy) https://www.helenmatthewslab.org/news/bscbbsdb-meeting-report monthly 0.5 2022-04-08 https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/0222dfe6-6c1c-49d8-b5d2-d46023249589/bscb.jpg Lab News - BSCB/BSDB meeting report - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://www.helenmatthewslab.org/news/welcome-victoria monthly 0.5 2022-03-11 https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/3d19e580-d210-4b3b-8181-e60c4820516d/Vic.jpg Lab News - Welcome Victoria! - The lab has doubled in size! https://www.helenmatthewslab.org/news/newlab monthly 0.5 2022-02-23 https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/2d8bf709-3847-4634-a748-b63259fb6631/new+lab.jpg Lab News - The lab opens it doors! - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://www.helenmatthewslab.org/home daily 1.0 2025-02-03 https://www.helenmatthewslab.org/team daily 0.75 2024-09-10 https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/1647352307592-3MFKSIK28OBS0NQD83X0/Vic2.jpg The Team https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/ed137eb4-ef9e-4b43-a89b-87ac4cdd8c29/Rachel.jpg The Team https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/91566219-8152-42a7-8acc-69854987bebf/Meg.jpg The Team https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/5a37d091-2b04-4c3c-bfb3-c64ddbf5761d/Bella.jpg The Team https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/e430a01e-5b27-4049-9175-a774c545c754/Helen+Matthews+headshot.jpg The Team https://www.helenmatthewslab.org/our-research daily 0.75 2024-10-02 https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/cf6077cb-6672-457e-9fe2-afbf542e4633/xz+Oscar.gif Research - HeLa cell rounding up and dividing - Actin cytoskeleton is labelled in green and DNA in red When they divide, cells undergo a series of dramatic shape changes. They round up as they enter mitosis, before elongating and dividing in two. Cells also change their mechanical properties as they divide allowing them to exert force against their environment (Taubenberger 2020). These shape and mechanical changes are controlled by dynamic re-organisation of the actin cytoskeleton and cell-substrate adhesion throughout cell division. We are investigating how the cell shape and mechanics are regulated during cell division. To do this, we take a multidisciplinary approach combining cell biology and imaging with biophysical techniques, such as atomic force microscopy, to measure cells’ mechanical properties. We are studying cell division mechanics in the context of both single cells and in epithelial tissues, where cells must undergo change shape while maintaining cell-cell adhesion to preserve tissue integrity. We are using epithelial monolayer systems to understand the forces applied when cells divide within proliferative tissues. https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/af61d2df-e2ea-459b-b9ee-70b62b2d4bd0/zoom+out.png Research - Cell division in tumoroids- Actin is labelled in red, tubulin in green & DNA in blue (Image by Max Williamson) Cancer begins with an oncogenic mutation within a single cell. We are studying how the activation of oncogenic signalling pathways affects cell shape and mechanics, with a particular focus on the Ras family of oncogenes. Our published work (Matthews 2020, Ganguli 2023) showed how the activation of Ras oncogenes changes cell shape and mechanics during cell division. This helps cancer cells divide in confined conditions as well as altering the angle of cell division, leading to a breakdown of normal tissue structure. We are now investigating the molecular mechanisms by which Ras oncogenes perturb the actin cytoskeleton to promote tumour formation and ultimately, invasion and metastasis. https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/f19cb08c-9fd6-4a1e-9fcd-3c6d6cf49b54/Mia-PaCa-2+Cells%2C+DNA+and+Actin+3D+view.jpg Research Pancreatic ductal carcinoma (PDAC) has a poor survival rate and very few treatment options available for patients. 90% of PDAC tumours are driven by mutations in the KRAS oncogene. We want to understand how oncogenic KRAS signalling alters the cytoskeleton to promote cell division and invasion within the PDAC tumour microenvironment. We also investigating how cell shape and mechanics affect the response of PDAC cells to therapy, including cell-cycle targeting chemotherapies as well as new inhibitors that directly target mutant KRAS. We hope to identify molecular mechanisms that underlie intrinsic and acquired resistance to PDAC cancer therapy, which can help to inform smarter treatments in the future. https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/1645557686544-9NF54729ONQJPOC7TDA1/royal+soc.png Research https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/1645557877539-NZKOAXWYAGZT0S6UC4JA/sheffield.jpg Research https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/1645558008457-W5I5347PR8UQHVFPKSI0/wellcome-logo-black.jpg Research https://www.helenmatthewslab.org/publications daily 0.75 2023-06-21 https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/577d7d6b-acf2-4c74-bf07-1d87d5c4da1b/cadart.png Publications Cadart, C., Zlotek-Zlotkiewicz, E., Le Berre, M., Piel, M. and Matthews, H.K. (2014) Exploring the function of cell shape and size during mitosis. Developmental Cell. 29, 159-69 https://doi.org/10.1016/j.devcel.2014.04.009 We discussed how cell rounding at mitosis facilitates cell division by ensuring proper mitotic spindle formation and positioning. https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/6044d027-433c-48fd-8252-dd7c3e03c080/matthews20.png Publications Matthews, H.K., Ganguli, S., Plak, K., Taubenberger, A., Win, Z., Williamson, M., Piel, M., Guck, J. and Baum, B. (2020) Oncogene activation alters cell shape and mechanics to facilitate cell division in confinement. Developmental Cell 52, 563-573 DOI: 10.1016/j.devcel.2020.01.004 We discovered that activation of Ras oncogenes enhances cell rounding and stiffening at mitosis, allowing cells to successfully divide in confined micro-environments, similar to those found in tumours. https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/a65fba0f-0be3-43bd-98df-95bc996493bb/dix.jpg Publications Dix, C.L.*, Matthews, H.K.*, Uroz, M., McLaren, S., Wolf, L., Heatley, N., Win, Z., Almada, P., Henriques, R., Boutros, M., Trepat, X. and Baum, B. (2018) The role of mitotic cell-substrate adhesion re-modeling in animal cell division. Developmental Cell. 45, 132-145. https://doi.org/10.1016/j.devcel.2018.03.009 We showed how focal adhesion complexes are disassembled in early mitosis but how cells remain attached to the substrate through beta1-integrin-rich puncta, which are essential to guide post mitotic respreading. https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/885d46c0-2df2-4233-b713-83302e5a07e9/debruin.png Publications Matthews, H.K., Bertoli, C. & de Bruin, R.A.M. Cell cycle control in cancer (2022) Nature Reviews Molecular Cell Biology 23, 74–88 https://doi.org/10.1038/s41580-021-00404-3 In this review, we present an overview of the regulation of cell cycle checkpoints in cancer and how they can be targeted therapeutically for cancer treatment. https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/b297f105-51b4-482d-aa2b-ca892f607c11/Ganguli+23.jpg Publications Ganguli, S., Wyatt, T., Nyga, A., Lawson, R.H., Meyer, T., Baum, B. and Matthews, H.K. (2023). Oncogenic Ras deregulates cell-substrate interactions during mitotic rounding and respreading to alter cell division orientation. Current Biology IN PRESS 20 Jun 2023 https://doi.org/10.1016/j.cub.2023.05.061 We showed how an oncogene, RRAS, deregulates substrate attachment during mitosis leading to out-of-plane cell divisions loss of epithelial tissue structure https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/94f1c542-146f-464c-b2fd-49c8699066ef/Matthews12.png Publications Matthews, H.K., Delabre, U., Rohn, J.L., Guck, J., Kunda, P. and Baum, B. (2012) Changes in Ect2 localization couple actomyosin-dependent cell shape changes to mitotic progression. Developmental Cell. 23, 371–83 https://doi.org/10.1016/j.devcel.2012.06.003 We identified a key molecular regulator of cell rounding in mitosis, the RhoGEF, Ect2, which forms a link between the cell cycle control machinery (Cdk1) and the acto-myosin reorganization that occurs at mitotic entry. https://images.squarespace-cdn.com/content/v1/6215100b2c8be92692201960/970ab42e-c5f8-41b3-92d5-e8b3a01e1e55/taubenberger.png Publications Taubenberger, A.V., Baum, B. and Matthews, H.K. (2020) The Mechanics of Mitotic Cell Rounding. Frontiers in Cell and Developmental Biology. 8:687. https://doi.org/10.3389/fcell.2020.00687 In this review we discussed how to measure cell mechanical properties in mitosis, the molecular mechanisms of mitotic stiffening and the consequences of these mechanical changes for cell division in healthy tissues and tumours. https://www.helenmatthewslab.org/contact daily 0.75 2022-03-15