Forces in cancer: interdisciplinary approaches in tumour mechanobiology

Dr Peter Friedl, Radboud University Nijmegen Medical Centre, The Netherlands, and The University of Texas, MD Anderson Cancer Center, USA

Dr 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.

Dr Pere Roca-Cusachs, Institute for Bioengineering of Catalonia, Spain

Pere 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.

Dr Sophie Acton, MRC-Laboratory for Molecular Cell Biology, University College London, UK

Dr 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.

Professor Alexander Bershadsky, Mechanobiology Institute, National University of Singapore, Singapore, and Weizmann Institute of Science, Israel

Alexander 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.

Professor Viola Vogel, ETH Zürich, Switzerland

Viola 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. 

Professor Dennis E Discher, University of Pennsylvania, USA

Dennis 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.

Dr Shelly Peyton, University of Massachusetts Amherst, USA

Shelly 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.

Dr GV Shivashankar, Mechnobiology Institute-National University of Singapore, Singapore

Shivashankar 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.

Dr Jan Lammerding, Cornell University, USA

Jan 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.

Professor Michael Sheetz, Mechanobiology Institute, National University of Singapore, Singapore

Professor 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.

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. 

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.