Poole Group: Cellular Mechanotransduction

The Poole group are interested in how cells can "feel" their surroundings. Our research seeks to identify how cells sense and respond to changing mechanical inputs by identifying the molecules that can convert forces into electrical or biochemical signals that influence cell behaviour. Her research team is focused on two streams of research 1) characterising force sensing in cancer cells and 2) investigating what happens to our cells in microgravity (when the influence of Earth's gravity is ablated).

Force sensing in cancer cells

When solid tumours develop, there are many changes in the mechanical properties of both the cells and their surroundings. These mechanical changes can lead to a local stiffening of tissue around a tumour (as seen in the development of breast tumours, detected by feeling for lumps of stiffened tissue). This tissue stiffening can also promote progression of the disease. Our question is: what are the molecular force sensors in cancer cells that can sense and respond to these changes in mechanics? Our research has identified new force sensing molecules that influence cell migration and that may influence the initial steps of the metastatic cascade, where cancer cells break from a tumour mass and invade the surrounding tissue. We are currently working to understand precisely how these force sensors are activated and to identify the specific role of this mechanical signalling in the dissociation of cells from a tumour mass. The long term goal of this research is to identify ways to target force sensing in cancer cells to improve patient outcomes.

All life on Earth has evolved under the persistent pull of Earth's gravitational field. While life can be sustained in reduced gravity environments (such as the microgravity experienced on the International Space Station) there are significant disruptions in human physiology that have negative impacts on health and performance. These impacts on human health have been relatively well defined by studying the impact of extended stays in microgravity on astronauts but we do not yet know the mechanisms by which these changes occur. Kate's team are investigating how disruptions in force sensing and cellular structures can lead to changes in cellular function when cells are exposed to simulated microgravity. The overall goal of this work is to identify how human health and performance is negatively impacted, at the molecular and cellular level, by reduced gravity environments, with the goal to identify ways to counter these negative effects, thus increasing human access to space.

1. Amrutha Patkunarajah*, Jeffrey H Stear*, Mirko Moroni, Lioba Schroeter*, Jedrzej Blaszkiewicz*, Jacqueline LE Tearle, Charles D Cox, Carina Fürst, Oscar Sánchez-Carranza, María del Ángel Ocaña Fernández, Raluca Fleischer, Murat Eravci, Christoph Weise, Boris Martinac, Maté Biro, Gary R Lewin, KATE POOLE (2020) TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration eLife 9:e53308 (2020) https://doi.org/10.7554/eLife.53308, opens in a new window
2. Sampurna Chakrabarti, Jasmin D Klich, Mohammed A Khallaf, Amy J Hulme, Oscar Sánchez-Carranza, Zuzanna M Baran, Alice Rossi, Angela Tzu-Lun Huang, Tobias Pohl, Raluca Fleischer, Carina Fürst, Annette Hammes, Valérie Bégay, Hanna Hörnberg, Rocio K Finol-Urdaneta, KATE POOLE, Mirella Dottori, Gary R Lewin. Touch sensation requires the mechanically gated ion channel ELKIN1. Science (2024) 383:992-998. DOI: https://www.science.org/doi/10.1126/science.adl0495
3. M Rocio Servin-Vences*, Mirko Moroni, Gary R Lewin, KATE POOLE. Direct measurement of TRPV4 and PIEZO1 activity reveals multiple mechanotransduction pathways in chondrocytes. eLife 6:e21074. (2017) https://doi.org/10.7554/eLife.21074, opens in a new window
4. Navid Bavi*, Jessica Richardson*, Celine Heu, Boris Martinac, and KATE POOLE. PIEZO1-Mediated Currents Are Modulated by Substrate Mechanics. ACS Nano 13, 11, 13545–13559. (2019) https://doi.org/10.1021/acsnano.9b07499, opens in a new window
5. K POOLE. The diverse physiological functions of mechanically activated ion channels in mammals. Annual Review of Physiology (2022) 84, 307-329. DOI:10.1146/annurev-physiol-060721-100935