KeyNote Speakers
Yolanda Prezado
Biography:
Yolanda Prezado is a research professor at the Centre for Research in Molecular Medicina and Chronic Diseases (CiMUS), in Spain and a senior researcher at the Institut Curie (France). She is a research director at the French National Center for Scientific Research (CNRS) (on leave) and head of the interdisciplinary team New Approaches in Radiotherapy (NARA). She has a multidisciplinary background. She received her Ph.D. in Physics from the University of Santiago de Compostela, Spain, in 2003. She is a Medical Physics expert (board certified in Spain and France). She did her Medical Physics residency at Hospital of Salamanca (Spain, 2004-2007), and later worked at Hospital of Pamplona until she was recruited as a beamline scientist at the Biomedical Beamline at the European Synchrotron Radiation Facility. Since 2011 she has been a permanent scientist at CNRS.
Her main interests are innovative radiotherapy techniques, combined radio-immunotherapies, radiobiology, and small field dosimetry. Her main research focus are spatially fractionated radiation therapy and proton therapy. One of their main projects is proton minibeam radiation therapy, funded by the European Union via an ERC consolidator grant. She has been the chair of the scientific committee of the European Federation of Medical Physicists from 2019 to 2021 and is the deputy spokesperson of the International Biophysics Collaboration. She has served on many committees and working groups. Her work in proton therapy has been rewarded with the Mr et Mme Peyre prize of the French Academy of Sciences in 2021.
Talk title: Spatially fractionated radiation therapy: current status of clinical and preclinical studies and knowledge gaps
Spatially fractionated
radiation therapy (SFRT) is an unconventional therapeutic approach
contradicting the classical paradigms of conventional radiation therapy
(1). The highly heterogeneous dose
distributions employed result in distinct radiobiological mechanisms which lead
to a remarkable increase in normal tissue tolerances. The more reported 800
patients treated with SFRT along numerous preclinical experiments suggest that
SFRT has the potential to increase the therapeutic index, especially in bulky and
radioresistant tumors. This lecture will provide a critical and holistic review
of SFRT, discussing not only the main clinical and preclinical findings but
also analyzing the main knowledge gaps.
Kevin Prise
Biography:
Professor of Radiation Biology, at the Patrick G Johnston Centre for Cancer Research at Queen’s University Belfast since 2007. Prior to this, he was Head of the Cell and Molecular Radiation Biology Group at the Gray Cancer Institute in Northwood, London. He received his PhD in Cell Biology and Biochemistry, from the University of Aberdeen, on the mechanisms of action of the chemotherapeutic methotrexate.
He has developed wide-ranging interests in radiation biology including research on low dose radiation risk, radiation quality, drug-RT combinations including nanoparticles, cell and tissue signalling mechanisms. His recent work is developing new biological based models for optimising the temporal and spatial aspects of advanced radiotherapies. A current focus is on the radiobiology of new laser-based approaches to probe extreme ultra-high dose-rate regimes.
He is a Past-President of the Radiation Research Society, a previous RRS Michael Fry award recipient and Friedrich Dessauer awardee of the German Radiation Research Societies. He was the 2018 Douglas Lea Lecturer, (Institute of Physics and Engineering in Medicine) and the 2018 Bacq and Alexander awardee from the European Radiation Research Society. He has supervised 54 PhD students and has published over 380 papers (h=68), with over 15,500 citations.
Talk title: The Radiobiology of Advanced Radiotherapy: A brief journey through space and time
Radiotherapy remains the mainstay of cancer therapy and its utility is continuing to rapidly expand. In recent years, it has gone through a series of technical revolutions which have allowed more and more precise targeting of dose to smaller and smaller “targets” with a range of different types of radiation. With the expansion of molecular (radionuclide) radiotherapy, its application is encompassing the whole gamut of the cancer therapy space from primary tumour to systemic disease and continuing to provide palliation, focussed on quality of life.
These technical advances have delivered significant changes in the spatial and temporal way that radiation is delivered into the human body. From a radiobiological perspective, we have incorporated these developments into assuring that pre-clinical studies fully mimic the clinical scenario and can rapidly feedback through reverse translation to the clinical interface. The spatial distribution of radiation exposure is now known to have important consequences, not only in targeted cells and tissues but in bystander cells and out-of-field abscopal effects each of which can have potential clinical impact.
Our understanding of radiation biology has previously been based on the timescale of its actions and the interrelationships between the physical (< 10-12 s), chemical (< 10 -1 s) and biological responses (> 10-1 s). Recent studies (>102 Gy/s) have shown that increasing dose-rate may play a critical role in these interactions with clinical potential, particularly with reducing normal tissue complications leading to improved therapeutic ratios. As well as conventional electron, photon and ion sources, laser-based technologies are now allowing the exploration of extreme dose-rate responses (>1010 Gy/s) opening up new opportunities to understand fundamental radiation mechanisms.
Overall, we are entering an exciting era for radiobiology as we start to integrate new knowledge on spatial and temporal effects and understand their potential applications.
Grant Stewart
Biography:
For nearly two decades the Stewart lab has studied how defects in DNA repair and replication contribute to genome stability using a combination of fundamental discovery science and human genetics. This research focus stemmed from the identification that hypomorphic hMRE11A mutations in patients cause an Ataxia-Telangiectasia (A-T)-like disorder, which provided vital evidence that an inability to detect and repair DNA double strand breaks (DSBs) is linked to neurodegeneration. Since this initial finding, the Stewart lab has discovered a multitude of new genome stability maintenance factors including MDC1, RNF168, TRAIP, BOD1L and DONSON. Critically, the identification of these factors has not only helped understand the pathological mechanisms underlying the development of disease, but it has also uncovered novel cellular pathways involved in maintaining cellular health by promoting genome stability e.g. the Mre11-Rad50-Nbs1 complex binds MDC1 at sites of DNA damage, which then helps relocalize RNF168 to trigger a ubiquitin-dependent DSB repair pathway. As a recognition of his work on the role of RNF168 in preventing genome instability and human disease, the Professor Stewart was awarded the Lister Institute Research prize (2009). To date, the Stewart lab has identified 10 new human disease genes, including most recently TONSL, RECQL1, SLF2 and SMC5, which have highlighted how different cellular stress response pathways protect the genome from distinct genotoxic insults and how this is important for maintaining normal foetal growth and development.
Talk title: ACTIN on a hunch when it comes to identifying novel DNA double-strand break repair disorders
Genome instability is a genetic trait that is common to all cancer. Abnormal repair of DNA damage is the most frequent underlying cause of genome instability and probably represents the most important event that contributes to, and in some cases initiates the development of cancer. Therefore, cellular pathways that control the repair of damaged DNA as well as those that regulate cell cycle checkpoints and the apoptotic machinery represent an inherent anti-tumour barrier that must be surpassed for a tumour to develop. However, it is becoming evident that defective DNA damage repair is a pathogenic process that contributes to the development of many diseases not just cancer and that this can affect organs and tissues in a variety of different ways.
The biochemical pathways involved in responding to damaged DNA are collectively termed the DNA damage response (DDR) and consist of those that regulate DNA damage detection, cell cycle checkpoint activation, DNA repair and apoptosis. Much of our insight about how different proteins are involved in regulating the DDR and the pathological consequences if this fails, has come about from the study of rare inherited human syndromes associated with genome instability and a high prevalence of cancer e.g. Ataxia-Telangiectasia and Nijmegen Breakage Syndrome. Studying these rare human diseases has not only provided a wealth of invaluable information about how defects affecting the DDR contributes to cancer development but it has also provided critical insight into how DNA damage drives neuro-degeneration, abnormal brain development, immune system dysfunction, growth failure and infertility.
Recently, we have identified a novel DNA double strand break repair disorder that sheds light on how the process of repairing DNA breaks is coordinated by nuclear actin. By studying this new disease we uncovered evidence that the actin network is not just a ubiquitous structural framework that dictates the shape and movement of cells but that it can be finely tuned to provide specificity to specific cellular processes.