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Forces in cancer: interdisciplinary approaches in tumour mechanobiology
Scientific discussion meeting organised by Dr Chris Bakal and Dr Julia Sero
In the last decade, research from diverse fields has converged to establish a fundamental concept: that physical forces play key roles in both the initiation and progression of cancer. This meeting will bring together an interdisciplinary group of pioneering scientists tackling cancer mechanobiology from many angles to present the latest developments in the field.
The speaker biographies and talk abstracts are available below. Recorded audio of the presentations will be available on this page after the meeting has taken place. Meeting papers are now published in Philosophical Transactions B.
Enquiries: Contact the Scientific Programmes team.
Organisers
Schedule
Chair
Dr Chris Bakal, Institute of Cancer Research, UK
Dr Chris Bakal, Institute of Cancer Research, UK
Chris Bakal is a Reader of Cell Form at the Institute of Cancer Research. He earned his BSc in Biochemistry from the University of British Columbia, and a PhD in Medical Biophysics from the University of Toronto. Chris’ postdoctoral work was performed in the Department of Genetics at Harvard Medical School, and the Computer Science and Artificial Intelligence Laboratory (CSAIL) at the Massachusetts Institute of Technology (MIT). His laboratory’s research is aimed at understanding how changes in cell shape drive tumorigenesis and metastasis. Towards these goals the Bakal laboratory uses quantitative single cell imaging technology, bioengineering, and computational methods. Dr Bakal’s contributions to the field of cancer cell biology include: the finding that cell shape can be used to infer the state of underlying signalling and transcriptional networks; that cell morphogenesis follows principles of dynamical systems; and that cell shape regulates the activity of key signalling proteins. These contributions have impacted our understanding of the role of cell shape changes in disease.
Chris was awarded the 2015 Cancer Research UK Future Leaders Prize. In 2014, he was awarded the Council for Systems Biology Merrimack Pharmaceuticals Prize, and in 2013 the British Association for Cancer Research Frank Rose Award. In 2007, Chris was awarded the Dorsett L. Spurgeon prize as one of the most promising postdoctoral fellows or junior faculty members at Harvard Medical School.
Outside of science Chris is a competitive track cyclist, and a former world-ranked downhill ski racer.
| 09:00 - 09:30 | Opening talk and introduction to the meeting | |
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| 09:30 - 10:00 |
Cell morphogenesis across scales, from molecular processes to cell shape control
A precise control of cell morphology is key for cell physiology, and cell shape deregulation is at the heart of pathological disorders, such as cancer. Cell morphology is intrinsically controlled by mechanical forces acting on the cell surface, to understand shape it is thus essential to investigate the regulation of cellular mechanics. In animal cells, shape is primarily determined by the cellular cortex, a thin network of actin filaments and myosin motors underlying the plasma membrane. The Paluch lab investigates how the mechanical properties of the cell surface arise from the microscopic organisation of the cortex, and how changes in these properties drive cell deformation. This talk will present methods to investigate cortex composition and nanoscale architecture, and discuss how cortical network mechanics are regulated. Using a combination of cell biology experiments, quantitative imaging and physical modelling, the aim is to understand the control of cell shape across scales. 
Professor Ewa Paluch, MRC-LMCB, University College London, and PDN, University of Cambridge, UK
Professor Ewa Paluch, MRC-LMCB, University College London, and PDN, University of Cambridge, UKEwa Paluch studied Physics at the Ecole Normale Supérieure in Lyon and obtained a PhD in Biophysics at the Curie Institute in Paris. In 2006, she started her research group at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden (joint appointment with the IIMCB, Warsaw). In 2013, she was appointed Professor of Cell Biophysics at the MRC LMCB, University College London. Since 2014, she has also been the head of the new Institute for the Physics of Living Systems, which promotes collaborations between physicists and biologists at UCL. She received the Hooke Medal from the British Society for Cell Biology in 2017 and was elected EMBO member in 2018. She has recently been elected Chair of Anatomy at the University of Cambridge and will be moving her laboratory to Cambridge in 2019. Ewa’s lab combines cell biology, biophysics, quantitative imaging and modelling to investigate the principles underlying cellular morphogenesis. |
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| 10:00 - 10:30 |
Mechanotransduction: from the cell surface to the nucleus
Mechanical forces affect many aspects of normal and tumour cell behaviour. To explore the physical role of the nucleus in mechanotransduction, nuclear-cytoskeletal connections were severed or cells were enucleated generating “cytoplasts”. The nucleus was not required for the establishment of cell polarity, migration in 1D or 2D, for chemotaxis or haptotaxis. However, cytoplasts were defective in migrating in 3D matrices. By several assays, cytoplasts exerted less force on the extracellular matrix and revealed decreased RhoA activity. Increasing substratum rigidity elevates RhoA activity. This has previously been attributed to Rho GEF activation downstream from integrins responding to actomyosin generated mechanical tension. However, the role of Rho GAPs has not been investigated in this pathway. In response to increasingly rigid substrata decreased p190RhoGAP activity was observed contributing to the overall activation of RhoA. Exploring the pathway involved revealed decreased expression of Rnd3/RhoE on rigid substrata. Rnd3 is a constitutively active Rho family member that antagonizes RhoA by activating p190RhoGAP. Driving Rnd3 expression stimulated p190RhoGAP and decreased RhoA activity. 
Professor Keith Burridge, University of North Carolina, USA
Professor Keith Burridge, University of North Carolina, USAProfessor Keith Burridge obtained his PhD in 1975 studying non-muscle myosins with Dennis Bray at the MRC Laboratory of Molecular Biology, Cambridge University. For his postdoc, he went to Cold Spring Harbor intending to work on SV40. However, upon his arrival, the director Jim Watson encouraged Keith to continue working on the cytoskeleton. In his first paper there, with Elias Lazarides, Keith identified alpha-actinin in non-muscle cells, showing it decorating stress fibres periodically and concentrating in structures that would come to be known as focal adhesions. Keith has continued to study focal adhesions, identifying and characterizing key components such as talin and paxillin. In 1981, Keith moved to the University of North Carolina, where he is now Kenan Distinguished Professor of Cell Biology and Physiology. For many years Keith has investigated Rho GTPase signalling pathways and how cells respond to mechanical force in the context of cell migration. |
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| 10:30 - 11:00 | Coffee break | |
| 11:00 - 11:30 |
Mechanisms underlying force-induced invasive migration of cancer cells
In this talk, three inter-related mechanisms underlying invasive migration of cancer cells are discussed. (1) A non-canonical form of invasive collective migration, displayed by the metastatic murine mammary carcinoma cell line 4T1. Benjamin Geiger shows that in sparsely plated cells, E-cadherin levels are reduced by ~50%, leading to a loose collective migration of the cells, that are interconnected by thin membrane tethers. Interestingly, knocking down E-cadherin by over 90% prevented tether formation in these cells, and greatly enhanced their individual migratory rate. Nevertheless, despite their enhanced migration the knocked-down cells became poorly metastatic and displayed reduced invasive properties ex vivo. These findings suggest that the moderate E-cadherin levels, present in wild-type 4T1 cells, play a key role in promoting cancer invasion and metastasis. The mechanism underlying this effect is discussed. (2) Environmental induction of cell invasion is also demonstrated in studies showing that breast carcinoma BT-474, exposed to specific populations of stromal fibroblasts, become highly invasive, and penetrate into the stromal monolayer. A search for the molecular basis of this invasion induction, identified a specific combination of two cytokines, namely IL1 and IL6, which can be secreted by different sub-populations of stromal cells, as the invasion promoting components. The cross-talk between these cytokines and their cooperation in inducing invasive EMT are discussed. (3) Invadopodia-mediated invasion. Invadopodia are actin-rich protrusions of the plasma membrane that attach to, penetrate into the extracellular matrix and induce its degradation. Invadopodia are commonly formed by cancer cells and are believed to promote tumour invasion and metastasis. In this study the functional bio-mechanics of invadopodia in cultured A375 melanoma cells, were investigated, using a combination of correlative microscopy approaches. This study demonstrated that the core actin bundle of invadopodia tend to form “under” the nucleus and to push against the nucleus and actually indent it. Estimation of the forces applied to the nucleus by the underlying invadopodia, based on the indentation profile and the viscoelastic properties of the nucleus, suggest that the pushing forces applied by the actin bundle to both the nucleus and to the matrix are in the ~20 nN/µm2 range. This cytoskeletal protrusion, combined with the adhesion to the matrix and the local matrix degradation activity are believed to contribute to the initial stages of the invasive process. 
Professor Benny Geiger, Weizmann Institute of Science, Israel
Professor Benny Geiger, Weizmann Institute of Science, IsraelProfessor Benny Geiger received a BS in Microbiology from Tel Aviv University in 1971 and an MSc in Immunology from the Hebrew University of Jerusalem in 1972. He obtained his PhD in Chemical Immunology from Weizmann Institute of Science in 1977. Professor Geiger has served on many positions including being a postdoctoral fellow at the University of California, San Diego in 1977–1979; visiting scientist at the Center for Cancer Research, MIT, from 1987–1988; Dean at the Feinberg Graduate School at Weizmann Institute of Science from 1989–1995; and presently Chair of the academic board at the Israel Science Foundation since 2009. |
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| 11:30 - 12:00 |
Extrinsic and intrinsic force regulates cancer progression, aggression and treatment
All cells experience force and possess mechanosensory mechanisms that enable them to detect mechanical stimuli and transduce these cues into biochemical signals that modify protein function and alter gene expression to influence cellular behaviour. Tumours have higher cell and tissue level forces and transformed cells exhibit perturbed mechanosensing. Valerie Weaver’s group has been studying the genesis of the altered tumour cell and tissue force and how cells sense and transduce mechanical cues to drive tumour formation and aggression and treatment response. Using an array of in vitro and in vivo models they found that the ECM progressively stiffens in peripheral tumours such as the breast, skin and pancreas mediated largely by increased collagen deposition, remodelling and crosslinking and induction of fibrosis. Even in tumours such as glioblastomas which do not exhibit fibrosis the ECM stiffens due to enhanced hyaluronic acid deposition and proteoglycan crosslinking. The Weaver group uniformly finds that a stiffened tumour ECM enhances integrin signalling to promote malignant transformation and tumour aggression that ultimately compromises treatment responsiveness. Consistently, inducing ECM tension or increasing integrin signalling promotes the malignant transformation of premalignant oncogenically-primed cells and drives the aggressiveness of tumours, whereas inhibiting ECM stiffening prevents tumour progression and reduces aggression. Importantly, when tumour cells are oncogenically transformed or loose expression of critical tumour suppressors they show a significant increase in actomyosin tension and enhanced integrin focal adhesion and growth factor receptor signalling. The high tumour cell tension fosters tumour progression and aggression in part by stiffening and remodelling the ECM. The stiff ECM also compromises the tissue vasculature to induce hypoxia and HIF1a to promote a mesenchymal-like phenotype that is highly resistant to therapy. The stiff ECM also modulates tumour immunity and regulates levels of key repressors that modulate anti-tumour cytotoxic responsiveness. 
Professor Valerie Weaver, University of California, San Francisco, USA
Professor Valerie Weaver, University of California, San Francisco, USADr Weaver is currently the Director of the Center for Bioengineering and Tissue Regeneration in the Department of Surgery, and is a Professor in the Departments of Surgery, Radiation Oncology and Bioengineering and Therapeutic Sciences at UCSF in San Francisco, CA. Her education took place in Canada, with a bachelor’s degree in Chemistry from the University of Waterloo, an Honors Bachelor’s and PhD degree in Biochemistry from the University of Ottawa with a two year postdoctoral training at the Institute for Biological Sciences, National Research Council of Canada and a 5 year postdoctoral tenure in Cancer Cell Biology at the Lawrence Berkeley National Laboratory at UC Berkeley with Dr Mina J Bissell. Dr Weaver was recruited to the University of Pennsylvania in Philadelphia where she joined the faculty in the Department of Pathology as an Assistant Professor and was appointed a full member of the Institute for Medicine and Engineering. In mid-2006 she relocated to UCSF in San Francisco as an Associate Professor in the Department of Surgery with a joint appointment in Anatomy to take on the Directorship of the Center for Bioengineering & Tissue regeneration. She was invited to join the UCSF Cancer Center and Stem Cell Programs in 2007 and was cross appointed to the newly formed Department of Bioengineering and Therapeutic Sciences in 2008 and was promoted to full Professor in 2010. Dr Weaver has over 20 years of experience in leading interdisciplinary research in oncology, including leadership of significant program projects including the Bay Area Physical Sciences and Oncology program and the UCSF Tumor Microenvironment Brain Program that merge approaches in the physical/engineering sciences with cancer cell biology and emphasise the role of the tumour microenvironment. Dr Weaver has been recognised for her research and leadership through receipt of several awards including the DOD BCRP Scholar award in 2005 and the DOD BCRP Scholar expansion award in 20013 for exceptional creativity in breast cancer research and the ASCB WICB Midcareer award for sustained excellence in cell biology research in 2014. Most recently she was elected as the chair of the AACR TMEN working group in 2015 and she was elected to be a fellow of the American Society for Cell Biology in 2017. Her research program focuses on the contribution of force, cell-intrinsic as well as extracellular matrix, to breast, pancreatic and glioblastoma tumour development and treatment. She also have an active research program exploring the interplay between cell and tissue level force and human embryonic stem cell differentiation. |
Chair
Dr Julia Sero, Institute of Cancer Research, UK
Dr Julia Sero, Institute of Cancer Research, UK
Dr Julia Sero studied cell and molecular biology at Penn State University and the University of Glasgow, and worked as an intern for many summers in microscopy and tissue engineering labs at Carnegie Mellon University. She then worked as a research assistant at MIT studying the genetics of cancer and development in mice with Jackie Lees. Dr Sero did her PhD with Donald Ingber at Harvard Medical School, using micropatterning to study cell adhesion and directional migration. In 2010, Julia joined Chris Bakal at the Institute of Cancer Research to investigate the dynamics of mechanosensitive transcriptional regulators as a function of cell shape. She is currently working with Molly Stevens's group at Imperial College to investigate cell movement and signalling in the context of bioengineered materials.
| 13:00 - 13:15 | Introduction to session talk | |
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| 13:15 - 14:15 |
Tissue regeneration, stem cells and cancer: roles of the mechanotransducers YAP/TAZ
Stefano Piccolo studies how cells sense their environment and use this information to build and maintain tissues with specific form, size and function, and how these systems are corrupted in diseases. At the centerpiece of these events is the activity of the transcriptional coactivators YAP and TAZ. Enhanced YAP/TAZ activity is emerging as a hallmark of multiple human tumours. Stefano will discuss the cell and tissue-level mechanisms that lead to unrestrained YAP/TAZ activity, in turn essential for tumour formation and for tissue regeneration upon injury. He will also present new evidence on the function of YAP/TAZ in regulating the biology of normal somatic stem cell explanted from adult tissues. 
Stefano Piccolo, Padua University, Italy
Stefano Piccolo, Padua University, ItalyDr Piccolo is Professor of Molecular Biology at the University of Padua School of Medicine. Dr Piccolo unveiled new mechanisms by which cells sense their environment and use this information to build and maintain tissues with specific form, size and function. Dr Piccolo also showed how disruption of these homeostatic mechanisms leads to tumor formation, progression and metastasis. Current main research topics are on Mechanotransduction, Wnt and Hippo pathways and how these signals regulate adult stem cells and cancer stem cells. |
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| 13:45 - 14:15 |
CDK1 inhibition is the trigger for remodelling of adhesion complexes in G2 phase of the cell cycle
In most tissues, anchorage-dependent growth and cell cycle progression are dependent on the engagement of cells with extracellular matrices via integrin receptor adhesion complexes. In a highly conserved manner, cells disassemble adhesion complexes, round up, and retract from their surroundings prior to division, suggestive of a primordial link between the cell cycle machinery and the regulation of cell-extracellular matrix adhesion. In this talk, Martin Humphries demonstrates that CDK1, a promiscuous serine/threonine kinase and master regulator of the cell cycle, mediates this link. CDK1, in complex with cyclin A2, has an interphase role in promoting adhesion complex and actin cytoskeleton organisation, and it also mediates a large increase in adhesion complex area as cells transition from G1 into S. Adhesion complex area starts to decrease early in G2 and disassembly occurs several hours prior to mitosis. This loss requires elevated cyclin B1 levels and is caused by inhibitory phosphorylation of CDK1-cyclin complexes. The inactivation of CDK1, which prevents phosphorylation of its myriad substrates, is therefore the trigger that initiates remodelling of adhesion complexes and the actin cytoskeleton in preparation for rapid entry into mitosis. 
Professor Martin Humphries FMedSci, University of Manchester, UK
Professor Martin Humphries FMedSci, University of Manchester, UKMartin Humphries is Professor of Biochemistry at the University of Manchester. He carried out postdoctoral research at the Howard University Cancer Center, Washington, DC, USA and at the National Cancer Institute, NIH, Bethesda, MD, USA. In 1988, he returned to Manchester and held Wellcome Trust Senior and Principal Research Fellowships. Martin was a co-founder of the Wellcome Trust Centre for Cell-Matrix Research, which he directed from 2000–2009. He is a Fellow of the Academy of Medical Sciences and a member of Academia Europaea. Adhesion of cells, either to other cells or to the tissue proteins that surround them in the body, is essential for multicellular life. The work conducted in Martin’s lab uses genome-level techniques to study the ways in which adhesion controls cell behaviour. Over the past five years, discoveries have been made in three areas: the receptor-transduced signals that control normal and tumour cell movement, the identity of force sensors within cells, and the mechanisms of cellular sensing of their microenvironment in disease. Current research is focused on the links between microenvironmental rigidity, adhesion signalling and cell proliferation in pancreatic ductal adenocarcinoma. |
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| 14:15 - 14:45 |
The dark side of fibroblast force
Tumour microenvironment plays an important role in the tumour progression. It is made of extracellular matrix (ECM), blood vessels, immune cells and cancer-associated fibroblasts (CAFs). Besides biochemical signals, mechanical forces from microenvironment also play a role in tumour progression. CAFs have enhanced contractility and capacity to synthesize, deposit and crosslink ECM making stroma stiffer. Thus, by accumulating around the tumour, they could provide a physical barrier constraining tumour expansion. However, it has been shown that by exerting mechanical forces on the ECM, CAFs also enhance tumour invasion. These antagonistic roles of forces produced by CAFs in tumour progression will be discussed. 
Dr Danijela Matic Vignjevic, Institute Curie, France
Dr Danijela Matic Vignjevic, Institute Curie, FranceDanijela Matic Vignjevic was trained as a molecular biologist at University of Belgrade, Serbia and University of Wisconsin-Madison, USA. She did her PhD in cell biology, working on the actin cytoskeleton during cell migration in the lab of Gary Borisy at Northwestern University, Chicago, USA. She then did a post-doc in the lab of Daniel Louvard at Institut Curie, working on mouse models for colon cancer metastasis as a HFSP fellow and later as INSERM researcher. She started her independent team at Institut Curie in 2013 when she got interested in how epithelial cells interact with their microenvironment in homeostasis and cancer invasion. Her research strategy combines molecular and cell biology techniques with live-cell imaging using different model systems such as 2D and 3D in vitro cell cultures; tissue slices cultured ex vivo; and different transgenic mouse models. |
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| 14:45 - 15:15 | Tea break | |
| 15:15 - 15:45 |
Endocytic control of mechanics, collective motion and cancer progression
Collective motility is ruled by both biochemical and physical interactions that cells establish among each other and with their environment. An emerging framework to interpret these interactions in unifying principles is the notion of cell jamming. During collective motility cells can flow like a fluid, but as density rises, the motion of each cell is constrained by the crowding due to its neighbours. At a critical density, motility ceases and collectives rigidify undergoing a liquid (unjammed)-to-solid (jammed) transition, herein referred to as UJT. This transition is thought to ensure proper development of barrier properties in epithelial tissues, but also to act as a tumour suppressive mechanism. The reverse, JUT might, instead, represent an alternative gateway to cell migration, enabling tissues to escape the caging imposed by the crowded cellular landscape of mature epithelia. The general validity of this physical framework and of JUT, however, remains to be verified. Even less understood is how cells control such phase transitions. In this talk, Giorgio Scita will address these issues and discuss whether the transition between “solid” and “liquid” locomotory states is an alternative or complementary gateway to epithelial-to-mesenchymal transition (EMT) to account for the plastic remodelling of epithelial tissues in physiology and pathology. 
Dr Giorgio Scita, IFOM, FIRC Institute of Molecular Oncology, Italy
Dr Giorgio Scita, IFOM, FIRC Institute of Molecular Oncology, ItalyGiorgio Scita obtained his PhD in Food Chemistry and Technology at the University of Parma, Italy, in the Department of Biochemistry. He did his postdoctoral training at the University of California, Berkeley and at the National Cancer Institute (NCI) of the National Institutes of Health (NIH). In 1995, he returned to Italy, to the European Institute of Oncology (IEO), Milan. In 2001, he became Principal Investigator at the IFOM Foundation, the FIRC Institute of Molecular Oncology, Milan. In 2006, he was appointed associate professor of General Pathology at the School of Medicine of the University of Milan. His primary research interest has been on dissecting basic mechanisms of cell migration focusing on signalling leading to spatial and temporal regulation of actin dynamics: the powerhouse for cell motility. More recently, he has been investigating the impact of endocytic networks on the biomechanics of collective cell migration, tumor plasticity and dissemination. |
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| 15:45 - 16:15 |
Cell collision geometry is critical for the emergence of extracellular matrix anisotropy
The organisation of the extra-cellular matrix (ECM) is crucial in determining both tissue structure and function. Many matrix proteins are organised into fibrillar structures with diameters in the range of 10-100nm and lengths in the range 10-100μm. Higher levels of organisation extending into the millimetre scale are also observed with aligned anisotropic matrices found in many tissues and pathologies, such as cancer and fibrosis. How such aligned ECM is generated is not well understood. Erik Sahai has undertaken a comprehensive survey of fibroblastic cells comparing those that generate highly aligned anisotropic matrices with those that don’t. His group has found that higher order alignment enables the coordination of traction forces and thereby millimetre scale collagen re-organisation. Detailed analysis of the emergence of aligned matrices reveals an unexpected role for cell collisions in coordinating ECM geometry. Further, combined RNAseq analysis reveals the transcriptional regulatory network that enable this behaviour. 
Dr Erik Sahai, Francis Crick Institute, London, UK
Dr Erik Sahai, Francis Crick Institute, London, UKErik Sahai is the head of the Tumour Cell Biology laboratory at the Francis Crick Institute in London. Erik obtained his PhD with Richard Treisman in London studying RhoGTPases and their effectors. He then carried out post-doctoral work in both London (Chris Marshall) and New York (John Condeelis). Following this training, Erik set up his own group at the Cancer Research UK London Research Institute in 2004 and then transferred to the Francis Crick Institute in 2015. His research is focused on the spread of cancer through the body and responses to cancer therapy. In particular, his group is interested in stromal fibroblasts and their interplay with both tumour and immune cells. To study these problems his group uses a wide range of techniques from computational modelling of cell migration, through conventional cell and molecular biology, to intravital imaging of mouse tumours and live analysis of patient derived material. Erik’s contributions have been recognised by the award of the Hooke Medal, and election to EMBO and the European Academy of Cancer Sciences. He serves on the editorial board of several journals, including Journal of Cell Biology, Oncogene, and Journal of Cell Science. |
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| 16:15 - 17:00 |
Summary
Dr Chris Bakal, Institute of Cancer Research, UK
Dr Chris Bakal, Institute of Cancer Research, UKChris Bakal is a Reader of Cell Form at the Institute of Cancer Research. He earned his BSc in Biochemistry from the University of British Columbia, and a PhD in Medical Biophysics from the University of Toronto. Chris’ postdoctoral work was performed in the Department of Genetics at Harvard Medical School, and the Computer Science and Artificial Intelligence Laboratory (CSAIL) at the Massachusetts Institute of Technology (MIT). His laboratory’s research is aimed at understanding how changes in cell shape drive tumorigenesis and metastasis. Towards these goals the Bakal laboratory uses quantitative single cell imaging technology, bioengineering, and computational methods. Dr Bakal’s contributions to the field of cancer cell biology include: the finding that cell shape can be used to infer the state of underlying signalling and transcriptional networks; that cell morphogenesis follows principles of dynamical systems; and that cell shape regulates the activity of key signalling proteins. These contributions have impacted our understanding of the role of cell shape changes in disease. Chris was awarded the 2015 Cancer Research UK Future Leaders Prize. In 2014, he was awarded the Council for Systems Biology Merrimack Pharmaceuticals Prize, and in 2013 the British Association for Cancer Research Frank Rose Award. In 2007, Chris was awarded the Dorsett L. Spurgeon prize as one of the most promising postdoctoral fellows or junior faculty members at Harvard Medical School. Outside of science Chris is a competitive track cyclist, and a former world-ranked downhill ski racer.
Dr Julia Sero, Institute of Cancer Research, UK
Dr Julia Sero, Institute of Cancer Research, UKDr Julia Sero studied cell and molecular biology at Penn State University and the University of Glasgow, and worked as an intern for many summers in microscopy and tissue engineering labs at Carnegie Mellon University. She then worked as a research assistant at MIT studying the genetics of cancer and development in mice with Jackie Lees. Dr Sero did her PhD with Donald Ingber at Harvard Medical School, using micropatterning to study cell adhesion and directional migration. In 2010, Julia joined Chris Bakal at the Institute of Cancer Research to investigate the dynamics of mechanosensitive transcriptional regulators as a function of cell shape. She is currently working with Molly Stevens's group at Imperial College to investigate cell movement and signalling in the context of bioengineered materials. |
| 09:00 - 09:30 |
Plasticity of cancer cell invasion and metastasis
Cancer cell migration is a plastic and adaptive process generating molecular and physical heterogeneity of migration mechanisms and metastatic routes, including single-cell and collective metastasis. When monitored in vivo using intravital multiphoton microscopy, tissue microniches provide invasion-promoting tracks that enable collective migration along tracks of least resistance. In regions of tissue confinement, invading cancer cells undergo a jamming transition towards collective migration and circulate as both individual cells and multicellular clusters for collective organ colonisation. Using multi-targeted interference with integrin adhesion systems, conversion from collective invasion to amoeboid single-cell dissemination followed by increased rates of lung colonisation was detected. Similar amoeboid dissemination was induced by hypoxia or stabilisation of hypoxia-inducible factor (HIF). The data suggest that metastatic cancer cells can undergo physicochemical reprogramming in response to encountered tissue environments, and thereby balance cell-intrinsic adhesion and mechanocoupling with encountered cues. Dissecting the microenvironmental determinants underlying individual-to-collective plasticity, and vice versa, will enhance to derive combined “antimigration” and cytotoxic therapies and combat metastatic transitions. 
Dr Peter Friedl, Radboud University Nijmegen Medical Centre, The Netherlands, and The University of Texas, MD Anderson Cancer Center, USA
Dr Peter Friedl, Radboud University Nijmegen Medical Centre, The Netherlands, and The University of Texas, MD Anderson Cancer Center, USADr Friedl received his MD degree from the University of Bochum (1992) and the PhD degree from the McGill University, Montreal (1996). Since 2007 he has been directing the Microscopical Imaging Centre of the Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, and since 2011 has held a joint-faculty position at the University of Texas MD Anderson Cancer Center, Houston, Texas, for preclinical intravital imaging of cancer lesions and their response to molecular targeted and immunotherapy. His research interest is the mechanisms and plasticity of cell migration in immune regulation and cancer metastasis, with emphasis on cell-matrix adhesion, pericellular proteolysis and cell-cell communication during migration. His laboratory identified pathways determining diversity and plasticity of cell migration, collective cancer cell invasion, and the contribution of migration pathways to immune defense and cancer resistance. His discoveries have provided a nomenclature for the different types of cell migration and their roles in building and (re)shaping tissue, with emphasis on inflammation, regeneration and cancer. His therapeutic preclinical studies focus on the intravital visualization of niches and mechanisms and strategies to overcome therapy resistance. |
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| 09:30 - 10:00 |
The molecular clutch model as a framework to understand integrin-mediated mechanotransduction
Cell proliferation and differentiation, as well as key processes in development, tumorigenesis, and wound healing, are strongly determined by the physical properties of the extracellular matrix (ECM). In this talk, Pere Roca-Cusachs’ approach combining molecular biology, biophysical measurements, and theoretical modelling to understand matrix rigidity sensing will be addressed. The roles of the properties under force of integrin-ECM bonds, and of the adaptor protein talin, will be discussed. This sensing can be understood through a computational molecular clutch model, which can quantitatively predict the role of integrins, talin, myosin, and ECM receptors, and their effect on cell response. Finally, it will be argued how this molecular clutch framework can explain cell sensing not only of substrate rigidity, but also of ECM spatial distribution of ligands, and how both rigidity and spatial sensing can be understood through the general principle of cell sensing of force loading rates. 
Dr Pere Roca-Cusachs, Institute for Bioengineering of Catalonia, Spain
Dr Pere Roca-Cusachs, Institute for Bioengineering of Catalonia, SpainPere Roca-Cusachs obtained his PhD in cellular biophysics in 2007 from the Medical School at the University of Barcelona. He then worked in the lab of Professor Michael Sheetz (Department of Biological Sciences, Columbia University) as a post-doctoral researcher until 2011. In 2011, he joined the University of Barcelona, where he is now an associate professor. In 2012, he obtained a joint position as group leader at the Institute for bioengineering of Catalonia (IBEC). He is a recipient of the EMBO Young Investigator Award. The research of his group focuses on unravelling the physical and molecular mechanisms by which cells detect and respond to mechanical force. |
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| 10:00 - 10:30 |
Crosstalk between fibroblastic stroma and leukocytes controls contractility and matrix remodelling
Sophie Acton’s interests lie in the communication between different cell types of the immune system, specifically the mechanisms controlling cellular trafficking, multicellular organisation and lymphoid organ architecture. The Acton lab uses the lymph node as their model system for investigating these processes. The lymph node is a highly organised and tightly controlled environment. The dynamic nature of lymph node swelling and contraction is critical to all immune responses and is not well understood. The group wants to understand the processes involved in lymph node swelling/expansion, and how these changes are coordinated. The interplay between immune cells and non-haematopeotic stromal cells is key to this process. There are many parallels between the cells interacting in the lymph node during an immune response, and the interactions happening in a tumour. Many of the same or similar cell types are present but a tumour is a hugely disorganised mess, and even worse, every tumour is different. One of the major benefits of their research is that they can use the lymph node model to both understand immunity, but also take those findings and apply that knowledge to the same cells in tumours, helping to understand cancer better, and hopefully find ways to harness our immune system to fight and destroy tumours. 
Dr Sophie Acton, MRC-Laboratory for Molecular Cell Biology, University College London, UK
Dr Sophie Acton, MRC-Laboratory for Molecular Cell Biology, University College London, UKDr Acton studied Pharmacology at the University of Bath, before spending a year working at Millenium Pharmaceuticals. She then started a PhD at the Cancer Research UK London research institute, studying mechanisms of metastasis in melanoma. Her first postdoc position was located at the Dana-Farber Cancer Institute at Harvard Medical School, working on mechanisms of dendritic cell migration. For her second postdoctoral training, back in London with Caetano Reis e Sousa, she worked on mechanisms of lymph node expansion supported by a Henry Wellcome Postdoctoral Fellowship. Dr Acton started her Stromal Immunology group at the MRC Laboratory for molecular cell biology at UCL in 2016, and her lab now is funded by Cancer Research UK and the European Research council. |
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| 10:30 - 11:00 | Coffee break | |
| 11:00 - 11:30 |
A unified pathway linking microtubules, myosin-II filaments and integrin adhesions
The interrelationship between microtubules and the actin cytoskeleton in mechanoregulation of integrin-mediated adhesions is poorly understood. Here, Alexander Bershadsky shows that the effects of microtubules on two major types of cell-matrix adhesions, focal adhesions and podosomes, are mediated by KANK family proteins connecting the adhesion protein talin with microtubule tips. Both total microtubule disruption and microtubule uncoupling from adhesions by manipulations with KANKs trigger a massive assembly of myosin-IIA filaments. Myosin-IIA filaments, augmenting the focal adhesions and disrupting the podosomes, are indispensable effectors in the microtubule-dependent regulation of integrin-mediated adhesions. Myosin-IIA filament assembly depends on Rho activation by the RhoGEF, GEF-H1, which is trapped by microtubules when they are connected with integrin-mediated adhesions via KANK proteins but released after their disconnection. Thus, microtubule capturing by integrin-mediated adhesions modulates the GEF-H1-dependent effect of microtubules on the myosin-IIA filaments. Subsequent actomyosin reorganisation then remodels the focal adhesions and podosomes, closing the regulatory loop. 
Professor Alexander Bershadsky, Mechanobiology Institute, National University of Singapore, Singapore, and Weizmann Institute of Science, Israel
Professor Alexander Bershadsky, Mechanobiology Institute, National University of Singapore, Singapore, and Weizmann Institute of Science, IsraelAlexander Bershadsky graduated from the Moscow State University with an MSc in mathematics and obtained his PhD in Cell Biology at the Cancer Research Center of the Russian Academy of Medical Sciences, where he continued to work until 1992. He published a book “Cytoskeleton” (1988, Plenum Press) together with J.M. Vasiliev. In 1992, Bershadsky moved to Israel and joined the Weizmann Institute of Science where he served sequentially as assistant, associate, and full professor, and is now (since 2017) a professor emeritus. Whilst at the Weizmann Institute, the Bershadsky laboratory was among the first to study the adhesion-dependent cell mechanosensitivity and microtubule-driven control of integrin-mediated adhesions. In 2009, he joined the Mechanobiology Institute (MBI) at the National University of Singapore where he currently holds a full-time position of Principal Research Scientist/Research Professor. Bershadsky’s research interests include cytoskeleton dynamics and self-organization, and the crosstalk between the cytoskeleton and cell adhesion. |
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| 11:30 - 12:00 |
Assessing the tensional state of fibronectin fibres in cancer stroma
Major transformations of extracellular matrix (ECM) accompany cancer progression, yet it remains poorly understood whether and how the ECM orchestrates the deterioration of healthy to pathological tissues. These processes are regulated by a complex interplay of cells with their ECM, whereby the biochemical composition as well as the physical features of ECM are well recognised to regulate diverse cell functions. Spatial mapping of the strain of ECM fibrils is crucial to learn how fibre stretching correlates with cell signalling events and disease progression. Progress was hampered though due to the lack of nanoprobes capable of sensing cell generated forces or the molecular strains at the tissue level. The Vogel lab thus took advantage of the evolution of bacterial adhesins that specifically target FN with high affinity, but only the relaxed but not stretched fibres, and exploited them to map the strain of ECM fibrils within histological cryosections of tumour stroma and in living animals. Spatial proximity analyses with other biomarkers provide first insights into functional correlations as further discussed in the presentation. 
Professor Viola Vogel, ETH Zürich, Switzerland
Professor Viola Vogel, ETH Zürich, SwitzerlandViola Vogel is a Professor in the Department of Health Science and Technology heading the Laboratory of Applied Mechanobiology at the ETH Zürich, Switzerland. Trained as a Physicist and with her graduate research conducted at the Max-Planck Institute for Biophysical Chemistry, she spent two years as postdoctoral fellow at the University of California Berkeley. As faculty member, she joined the Department of Bioengineering at the University of Washington/Seattle in 1990 and moved there through the ranks to Full Professor. She was the Founding Director of the Center for Nanotechnology at the University of Washington (1997-2003) prior to her move to Switzerland in 2004, where she initially joined the Department of Materials. She serves on various advisory boards worldwide and has received major honors and awards, including the Otto-Hahn Medal of the Max-Planck Society 1988, the “First Award” from the Institute of General Medicine (National Institutes of Health USA, 1993-98), the Julius Springer Prize 2006 for Applied Physics, the ERC Advanced Grant (European Research Council 2008-13), the International Solvay Chair in Chemistry Brussels 2012, and an Honorary Degree Doctor of Philosophy from Tampere University, Finland 2012. She also served as a Rapporteur for the Max-Planck Society, Physical-Chemical Technical Division (2012-2013), as Panel Member Representing the European Research Council at the World Economic Forum in Davos (2013), as Jury Member for the Queen of Elizabeth Prize for Engineering (2015), and is a Member of the World Economic Forum Global Agenda Council in Nanotechnology (2014-2016). She exploits nanotechnology tools to decipher how bacteria and mammalian cells and micro-tissues exploit mechanical forces to recognize and respond to material properties and their native environments. Her discoveries in single molecule and cell mechanics and how protein stretching switches their function, as well as in the field of mechanobiology have a wide range of technical and medical implications. In collaboration with clinicians, several technologies are currently carried towards preclinical studies. |
| 13:00 - 13:15 | Introduction to the session | |
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| 13:15 - 13:45 |
Genome variation across cancers scales with tissue stiffness: an invasion-mutation mechanism and implications for immune cell infiltration
Many different types of soft and solid tumours have now been sequenced, and meta-analyses suggest that genomic variation scales with the stiffness of the tumours’ tissues of origin. Since stiff solid tissues have higher density of fibrous collagen matrix, which should decrease tissue porosity, processes in proliferation could be affected and so could invasion into stiff tissues as the nucleus is squeezed sufficiently to enhance DNA damage. Although careful analyses continue to be required for rigorous conclusions about such DNA damage (eg 53BP1 seems a poor marker whereas gH2AX agrees with electrophoresis), diversification of a cancer genome after constricted migration is now clear in vitro and seems to involve loss of DNA repair factors. Understanding genome changes that give rise to neo-antigens is important to selection of cancer cell subpopulations (immunoediting) as well as to the development of immunotherapies. Monocytes/macrophages that might now be engineered to effectively attack cancer cells seem particularly relevant to understanding infiltration into solid tumours as well as the effects of microenvironment stiffness on factors that protect the genome such as the nuclear lamins. 
Professor Dennis E Discher, University of Pennsylvania, USA
Professor Dennis E Discher, University of Pennsylvania, USADennis Discher is the Robert D. Bent chaired Professor at the University of Pennsylvania and Director of a National Cancer Institute-funded Physical Sciences Oncology Center at Penn, where he has been since 1996. He is an elected member of the US National Academy of Medicine, the US National Academy of Engineering, and the American Association for the Advancement of Science. He earned his PhD jointly from UC Berkeley & UC San Francisco in membrane biophysics and splicing biochemistry, conducted computational biophysics studies as a Postdoctoral Fellow at University of British Columbia & Simon Fraser University, Vancouver, and holds appointments at Penn in Engineering & Applied Science as well as the Graduate Groups in Physics and Pharmacology. Additional honors and service include the Friedrich Wilhelm Bessel Award from the Humboldt Foundation of Germany, current Chair of the NIH Gene & Drug Delivery Study Section, and member of the Editorial Board for Science. |
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| 13:45 - 14:15 |
Tissue inspired hydrogels to understand breast cancer metastasis and drug resistance
Improved in vitro models are needed to better understand cancer progression and bridge the gap between in vitro proof-of-concept studies, in vivo validation, and clinical application. Many methods exist to create biomaterial platforms, including hydrogels, which Shelly Peyton’s lab use to study cells in contexts more akin to what they experience in vivo. Her lab has multiple approaches to create such biomaterials, based on combinations of poly(ethylene glycol) (PEG) with peptides and zwitterions. In this presentation, Shelly will discuss their findings in using these cell culture environments to understand the role of the extracellular matrix (ECM): ligand density, stiffness, geometry, etc, in controlling cancer cell innate drug response via adaptive signalling. 
Dr Shelly Peyton, University of Massachusetts Amherst, USA
Dr Shelly Peyton, University of Massachusetts Amherst, USAShelly Peyton is the Barry and Afsaneh Siadat Assistant Professor of Chemical Engineering at the University of Massachusetts, Amherst. She received her BS in Chemical Engineering from Northwestern University in 2002 and went on to obtain her MS and PhD in Chemical Engineering from the University of California, Irvine. She was then an NIH Kirschstein post-doctoral fellow in the Biological Engineering department at MIT before starting her academic appointment at UMass in 2011. Shelly Peyton leads an interdisciplinary group seeking to create and apply novel biomaterials platforms toward new solutions to grand challenges in human health. The group’s unique approach is using their engineering expertise to build simplified models of human tissue with synthetic biomaterials. These tissue mimics are engineered to capture a subset of the mechanical and chemical features of human tissue, and are cheap and reproducible. With these, they study how cell-material interactions in tissues affect drug response toward better patient outcomes. The group use these systems to understand 1) the physical relationship between metastatic breast cancer cells and tissues to which they spread, 2) how tissue-specific stem cells remodel tissues to facilitate metastasis, and 3) the role of matrix remodeling in drug resistance. Shelly is a Pew Biomedical Scholar, received a New Innovator Award from the NIH, and she was awarded a CAREER grant from the NSF. |
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| 14:15 - 14:45 |
Mechanical regulation of genome organisation and gene expression
Cells within the tissue microenvironment are highly heterogeneous and integrate both biochemical and physical signals to maintain homeostasis. However it is unclear how the mechanical constraints on cells (and thus their geometry) affect the micro-environmental regulation of genome programs. To address this question, the Shivashankar lab uses micro-patterned substrates to sculpt cell geometry and study its role in integrating micro-environmental signals such as cytokines and tissue compression. In this talk, GV Shivashankar will discuss an important layer of genome regulation resulting from the coupling between cell geometry and 3D organisation of chromosomes and their intermingling. The lab’s results show that the mechanical state of a cell dictates how cells integrate signals to control gene expression. Importantly, sustained growth of cells on such geometrically confined substrates results in novel routes to nuclear reprogramming and the regulation of cell-fate decisions. 
Dr GV Shivashankar, Mechnobiology Institute-National University of Singapore, Singapore
Dr GV Shivashankar, Mechnobiology Institute-National University of Singapore, SingaporeShivashankar is currently a Principal Investigator and Deputy Director of the Mechanobiology Institute, National University of Singapore. Shivashankar carried out his PhD research at the Rockefeller University (1994-1999) and Postdoctoral research at NEC Research Institute, Princeton USA (1999-2000). He started his laboratory at the National Center for Biological Sciences, TIFR- Bangalore, India (2000-2009) and was tenured in 2004. He then relocated to a tenured faculty position at the National University of Singapore in 2009. His laboratory studies the modular links between cell geometry and nuclear mechanics in regulating 3D chromosome organization and genetic information, and how alterations in such modular links can be used as physical biomarkers for cancer diagnostics. His scientific awards include: the Birla Science Prize (2006), The Swarnajayanthi Fellowship (2007). In addition, he was elected to the Indian Academy of Sciences (2010). More recently, he also heads the Joint Research Laboratory with the FIRC Institute of Molecular Oncology (IFOM), Milan, Italy and he was appointed as an IFOM-NUS Chair Professor in 2014. In 2017, he cofounded SCENMED Diagnostics@ - a digital nuclear mechanopathology platform for early cancer diagnostics. |
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| 14:45 - 15:15 | Coffee break | |
| 15:15 - 15:45 |
Squish and squeeze: the role of the nucleus and lamins in breast cancer metastasis
During cancer cell invasion and metastasis, tumour cells migrate through interstitial spaces as small as 2 µm in diameter. The deformability of the cell nucleus constitutes a rate-limiting factor in the passage of cells through such confined environments. Intriguingly, the expression of the nuclear envelope proteins lamin A/C, which are a major determinant of nuclear deformability, is misregulated in many cancers. Patient-derived breast tumour tissues and cell lines revealed significantly lower lamin A/C levels than normal tissues, with lamin A/C levels further reduced in particularly aggressive cell lines. Breast cancer cells with low lamin A/C levels had more deformable nuclei and migrated faster through confined environments than cells with high lamin A/C levels. Increasing lamin A expression in metastatic cells with normally low lamin A/C levels decreased cell proliferation and altered expression of proteins involved in cell adhesion, extracellular matrix remodeling, and cell metabolism, indicating additional mechanisms by which lamins can modulate cancer progression and impact both tumour cell invasion and outgrowth. Analysis of breast tumour tissue microarrays revealed that low levels of lamin A/C are associated with reduced disease-free survival. Insights gained from these studies could improve prognostic approaches and motivate novel therapeutic approaches to control metastatic disease in breast cancer. 
Dr Jan Lammerding, Cornell University, USA
Dr Jan Lammerding, Cornell University, USAJan Lammerding is an Associate Professor and Director of Graduate Studies in the Nancy E. and Peter C. Meinig School of Biomedical Engineering and the Weill Institute for Cell and Molecular Biology at Cornell University. After obtaining a Diplom Ingenieur degree in Mechanical Engineering in his native Germany, he completed his Ph.D. in Biological Engineering at the Massachusetts Institute of Technology studying subcellular biomechanics and mechanotransduction signaling in the laboratories of Roger Kamm and Richard T. Lee (Brigham and Women’s Hospital/Harvard Medical School). Following a brief postdoctoral fellowship in Dr. Lee’s laboratory, he started his faculty career at Harvard Medical School/Brigham and Women’s Hospital while also teaching in the Department of Biological Engineering at the Massachusetts Institute for Technology before joining Cornell University in 2011. The research in the Lammerding laboratory is focused on developing novel experimental techniques to investigate the interplay between cellular mechanics and function, with a particular emphasis on the cell nucleus and its response to mechanical forces. |
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| 15:45 - 16:15 |
Normalizing transformed cancer cells with cytoskeletal proteins not RTKs
A major hallmark of cancer cells is uncontrolled growth on soft matrices (transformed growth), which implies that cancer cells lack the ability to sense matrix rigidity. Our recent studies of fibroblasts show that local contractions by rigidity sensing modules block growth on soft surfaces but module depletion causes transformed growth. The contractile system involves many cytoskeletal proteins that must be correctly assembled for proper rigidity sensing. The Sheetz lab tested the hypothesis that cancer cells lack rigidity sensing due to their inability to assemble contractile modules because of altered cytoskeletal protein levels. In all transformed cancer cells tested, there were over ten-fold fewer rigidity-sensing contractions compared with normal fibroblasts. Restoring normal levels of cytoskeletal proteins restored rigidity sensing and rigidity-dependent growth in transformed cancer cells. In several cases, replenishing tropomyosin 2.1 (often depleted by miR-21) or depleting 3 (often overexpressed) caused normal growth on rigid and anoikis on soft surfaces. The process of anoikis was driven by death-associated protein kinase1 in a Tpm2.1 and talin1 head dependent process that was downstream of PTPN12 (PTP-PEST). Thus, the depletion of rigidity sensing modules enables growth on soft surfaces by preventing anoikis, which is an important factor in further cancer progression. 
Professor Michael Sheetz, Mechanobiology Institute, National University of Singapore, Singapore
Professor Michael Sheetz, Mechanobiology Institute, National University of Singapore, SingaporeProfessor Michael Sheetz is a pioneer in the emerging field of mechanobiology and recipient of prestigious prizes including the Lasker Prize for Basic Medical Research. As the Mechanobiology Institute’s founding Director, he has promoted research on molecular mechanisms of force sensing and cell motility during development, cancer and aging. Prof. Sheetz was trained in biophysical chemistry and has worked in the areas of cell biology and biomechanics where his lab has made several seminal findings including in vitro assays for myosin and kinesin motor proteins, the role of membrane tension in regulating motile functions and the molecular basis of rigidity sensing. Over the last 20 years he has taught the biophysical bases of cellular functions in The Cell as a Machine course that is offered internationally. |
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| 16:15 - 17:00 |
Closing talk
Dr Chris Bakal, Institute of Cancer Research, UK
Dr Chris Bakal, Institute of Cancer Research, UKChris Bakal is a Reader of Cell Form at the Institute of Cancer Research. He earned his BSc in Biochemistry from the University of British Columbia, and a PhD in Medical Biophysics from the University of Toronto. Chris’ postdoctoral work was performed in the Department of Genetics at Harvard Medical School, and the Computer Science and Artificial Intelligence Laboratory (CSAIL) at the Massachusetts Institute of Technology (MIT). His laboratory’s research is aimed at understanding how changes in cell shape drive tumorigenesis and metastasis. Towards these goals the Bakal laboratory uses quantitative single cell imaging technology, bioengineering, and computational methods. Dr Bakal’s contributions to the field of cancer cell biology include: the finding that cell shape can be used to infer the state of underlying signalling and transcriptional networks; that cell morphogenesis follows principles of dynamical systems; and that cell shape regulates the activity of key signalling proteins. These contributions have impacted our understanding of the role of cell shape changes in disease. Chris was awarded the 2015 Cancer Research UK Future Leaders Prize. In 2014, he was awarded the Council for Systems Biology Merrimack Pharmaceuticals Prize, and in 2013 the British Association for Cancer Research Frank Rose Award. In 2007, Chris was awarded the Dorsett L. Spurgeon prize as one of the most promising postdoctoral fellows or junior faculty members at Harvard Medical School. Outside of science Chris is a competitive track cyclist, and a former world-ranked downhill ski racer.
Dr Julia Sero, Institute of Cancer Research, UK
Dr Julia Sero, Institute of Cancer Research, UKDr Julia Sero studied cell and molecular biology at Penn State University and the University of Glasgow, and worked as an intern for many summers in microscopy and tissue engineering labs at Carnegie Mellon University. She then worked as a research assistant at MIT studying the genetics of cancer and development in mice with Jackie Lees. Dr Sero did her PhD with Donald Ingber at Harvard Medical School, using micropatterning to study cell adhesion and directional migration. In 2010, Julia joined Chris Bakal at the Institute of Cancer Research to investigate the dynamics of mechanosensitive transcriptional regulators as a function of cell shape. She is currently working with Molly Stevens's group at Imperial College to investigate cell movement and signalling in the context of bioengineered materials. |