Chairs
Dr Paola B. Arimondo, CNRS ETaC, France
Dr Paola B. Arimondo, CNRS ETaC, France
Dr Paola B. Arimondo studied Chemistry at the University of Pisa, Italy, and received a PhD in Biophysics at the MNHN in Paris. In 2001, she was recruited by the CNRS. Her research focused on the interactions between nucleic acids and proteins and their modulation by small chemical molecules, resulting in site-specific ‘DNA scissors’ in cancer cells. After a six-month sabbatical in 2005 at the University of California in Berkeley, she initiated a new project aiming at the epigenetic control of gene expression in cancers. In 2011, she was recruited to lead the Laboratory of Epigenetic Targeting of Cancer, a joint public-private Laboratory between the CNRS and Pierre Fabre Laboratories, in Toulouse, France. She now develops chemical modulators of DNA and histone methylation to study the aberrant epigenetic mechanisms in cancer and identify new targets or biomarkers. Dr Arimondo is co-author of 92 publications and of 9 patents, was awarded the ‘Médaille de Bronze’ of CNRS, ‘Prix de l’Encouragement’ of the French Société de Chimie Thérapeutique, and the ‘Marie Curie Excellence Award’ of the European Community. She is actually Oversea Fellow at the Churchill College in Cambridge UK.
09:00-09:30
Epigenetic dysfunctions in cancer: a cause or a consequence?
Professor Bozena Kaminska, Nencki Institute of Experimental Biology, Poland
Abstract
The epigenetic landscape is deregulated in cancer due to aberrant activation/ inactivation of enzymes maintaining and modifying the epigenome. Aberrations at the global histone level and/or specific histone modifications may produce distorted patterns of gene expression and malfunction of proteins that regulate chromatin structure. Recent whole genome studies demonstrated that histones and chaperone proteins harbour mutations that may result in gross alterations of the epigenome leading to genome instability. IDH1/2 (isocitrate dehydrogenase 1/2) mutations have been detected in hematologic malignancies and certain solid tumours. Point mutations in IDH1/2 confer a gain-of-function in cancer cells, resulting in accumulation of the D-2-hydroxyglutarate (D-2HG). High levels of D-2HG interfere with cellular metabolism and epigenetic regulation by inhibiting histone and DNA demethylases, which results in blocking cellular differentiation. Histone deacetylases (HDACs) are critical regulators of gene expression that promote chromatin changes by deacetylating histones. Aberrant regulation of HDACs contributes to malignant transformation and progression in many human cancers. Dysfunction of the histone lysine methyltransferase EZH2 occurs in numerous cancers. EZH2 a part of the polycomb repressive complex 2 which catalyses trimethylation of histone H3 lysine 27. It supports undifferentiated phenotype and blocks differentiation during embryonic development and carcinogenesis. Epigenetic-based mechanisms are reversible and 'resetting' the abnormal cancer epigenome by pharmacological compounds targeting epigenetic enzymes is a promising strategy. Several novel drugs targeting tumours with mutated IDH1/2/ and numerous HDAC inhibitors have been identified. These compounds cause cell cycle arrest or death, inhibit DNA repair and some entered clinical trials for cancer treatment.
Show speakers
Professor Bozena Kaminska, Nencki Institute of Experimental Biology, Poland
Professor Bozena Kaminska, Nencki Institute of Experimental Biology, Poland
Dr Bozena Kaminska is Professor at the Nencki Institute of Experimental Biology Warsaw and Director of the Postgraduate School of Molecular Medicine, Warsaw Medical University. She is a corresponding member of the Polish Academy of Sciences (2016). She did her PhD in biochemistry (1991) at the Nencki Institute (Warsaw, Poland) and postdoctoral training at the Department of Psychology, McGill University, Montreal, Canada (1994-1996). In 2001-2002 she was a visiting scientist at the Brain Research Institute, UCLA, USA. Kaminska's research group is focused on epigenetic modifications on chromatin, RNA and DNA and their involvement in cancer. She has discovered the role of innate immune cells in glioma progression, and studied epigenetic dysfunctions and chromatin modification pathways in brain tumours. She promoted 24 PhD students and is currently involved in 12 basic research and translational projects aiming at development of novel antitumour therapeutics. She is a co-founder of cancer drug discovery company GLIA and an elected member of Academia.net.
09:45-10:15
Epigenetic biomarkers
Professor Carmen Jerónimo, Portuguese Oncology Institute and University of Porto, Portugal
Abstract
An increasing body of evidence is implicating several epigenetic mechanisms as driving forces of neoplastic transformation. Among these, aberrant DNA methylation is, by far, the most widely studied, followed by deregulated expression of chromatin machinery proteins and non-coding RNAs, including microRNAs. Importantly, cancer-related epigenetic alterations may provide novel cancer biomarkers, intended for early detection and diagnosis, assessment of prognosis, and prediction of response to therapy. The importance of early diagnosis in Oncology has been emphasised and although current methodologies (such as cytology, histopathology, immunohistochemistry, etc) play a critical role, molecular markers may complement or, eventually, replace them if more effective. Because epigenetic alterations often precede the emergence of the malignant phenotype, they are advantageous for early cancer detection. They might also be detected in clinical samples, including those obtained by biopsy, as well from those obtained by non-invasive methods, such as urine. Moreover, early detection of cancer relapse before it manifests clinically (or on imaging during routine patient follow-up) might be accomplished through epigenetic-based biomarkers. Some epigenetic alterations have also been associated with tumour behaviour and may, thus, serve as prognostic biomarkers.
In this talk, Professor Jerónimo will focus on the major recent findings obtained by her research team regarding epigenetic mechanisms implicated in urological tumorigenesis as well as the potential usefulness of epigenetic-based biomarkers for detection and prognostication in these cancers.
Show speakers
Professor Carmen Jerónimo, Portuguese Oncology Institute and University of Porto, Portugal
Professor Carmen Jerónimo, Portuguese Oncology Institute and University of Porto, Portugal
Professor Carmen Jerónimo is Invited Associate Professor in Pathology and Molecular Genetics and the Director of the Master Course in Oncology at the University of Porto, as well as Head of the Cancer Epigenetics Group at the Portuguese Oncology Institute of Porto (IPO Porto), Portugal.
She obtained her BSc in Biology (1994), MSc in Oncology (1998), PhD in Biomedical Sciences (2001) and Habilitation in Pathology and Molecular Genetics (2011) at the University of Porto. She developed her PhD project at Johns Hopkins University School of Medicine (JHU), Baltimore, MD, USA, working on prostate cancer’s genetic and epigenetic alterations. From 2002 until 2007, she was a Post-doctoral Fellow and Invited researcher at IPO Porto, in collaboration with JHU, working on detection of neoplastic cells by DNA-based technology in clinical samples obtained from non-invasive or minimal invasive methods. In 2008 she established her independent group at IPO Porto, working on Cancer Biology and Epigenetics (FCT-2008 Science Program).
Professor Jerónimo is Associate Editor of Clinical Epigenetics and BMC Cancer and acts as ad hoc reviewer of several scientific journals. To the present date, she has authored or co-authored more than 100 international scientific publications published in prestigious journals, such as JNCI, JCO, Eur J Urol, Clin Can Res, Oncogene, Oncotarget, EJC, BJC and Epigenetics, and four book chapters. As scientific leader, she collaborated in a patent submission (Methods and biomarkers for detection of bladder cancer US 20130210011/ EP 2630261 A1/ WO 2012052844 A1), based in a study from her group in partnership with the Norwegian Radium Hospital and has participated in international projects funded by EU, within the Seventh Framework Programme (EpiDiaCan). She was MC substitute member of Action TD0905 (CMST) - Epigenetics: Bench to Bedside and presently she is MC member and Chair of Working group WG2 of COST Action CM1406 (CMST)- Epigenetic Chemical Biology (EPICHEM).
11:10-11:40
Epigenome approaches for identification of treatment resistance in cancer
Professor Lucia Altucci, University of Campania Luigi Vanvitelli, Italy
Abstract
Aberrant activity of epigenetic enzymes plays a role in tumorigenesis. Reversal of these aberrant modifications has emerged as a strategy for cancer treatment. By applying epigenome-based patient stratification, the group identified a set of chromatin areas predictive for standard treatment resistance in leukaemias. Professor Altucci reports that a novel dual-epidrug, as effective in standard treatment resistant cancers. The group identified both the mechanistic insights of this action and biomarkers that might turn into a differential diagnostic tool for leukaemia patients. Together, the group provides proof of concept for the use of epigenome profiling coupled to epi-drugs to ‘personalise’ precision medicine.
Show speakers
Professor Lucia Altucci, University of Campania Luigi Vanvitelli, Italy
Professor Lucia Altucci, University of Campania Luigi Vanvitelli, Italy
Professor Altucci studied for a degree in Medicine and Surgery, specialising in Medical Oncology, and a PhD in Molecular Pathology before taking up a postdoctoral position at the IGBMC in Strasbourg. Currently she is Professor of General Pathology at the University of Campania Luigi Vanvitelli, where she is also the Rector's delegate for research. Her research interests include translational medicine, mechanisms of tumorigenesis, differentiation and cell death. She is also interested in drug discovery. Professor Altucci has more than 180 peer-reviewed publications.
11:55-12:25
Environmental metals, epigenetics and cardiovascular risk: a population-based perspective
Dr Maria Tellez-Plaza, Hospital Clinic of Valencia University, Spain; Johns Hopkins Bloomberg School of Public Health, USA
Abstract
Cardiovascular disease is a major cause of mortality and morbidity world-wide. Current algorithms for cardiovascular risk prediction, which combine behavioural, clinical, and biochemical markers, are, however, of limited accuracy. Understanding novel factors and mechanisms for cardiovascular disease development can contribute to the identification of at-risk individuals, who could benefit the most from preventive interventions. Non-essential environmental metals are emerging as major contributing factors to cardiovascular health in study populations exposed to low or moderate metal dose through air, food or water. Moreover, metals accumulate in the body where they can induce long-term damages. Dr Tellez-Plaza will be discussing available evidence in support of metals as environmental determinants of both epigenetic markers and cardiovascular disease in general populations. The identification of epigenomic regions that are environmentally regulated and may be involved in pathways related to cardiometabolic risk can enable the implementation of both population-based and personalised strategies for the control of cardiovascular disease in the population. Moreover, several lines of evidence suggest that environmental exposures can influence health outcomes in subsequent generations, due to epigenetic changes. It is of interest, thus, to explore novel epigenetic approaches for prevention and treatment of disease, which may be relevant for future generations.
Show speakers
Dr Maria Tellez-Plaza, Hospital Clinic of Valencia University, Spain; Johns Hopkins Bloomberg School of Public Health, USA
Dr Maria Tellez-Plaza, Hospital Clinic of Valencia University, Spain; Johns Hopkins Bloomberg School of Public Health, USA
Dr Maria Tellez–Plaza, is a physician specialist in Preventive Medicine and Public Health with a PhD in Epidemiology from Johns Hopkins University who joined the Institute for Biomedical Research Hospital Clinic de Valencia, Spain, as Tenure-track Investigator. In addition, she holds an Adjunct Professor position in the Autonomous University of Madrid, where she coordinates a course in the MPH program, and an Adjunct Assistant Professor position at the Johns Hopkins University, where she maintains active collaborations with scientists from the Departments of Epidemiology and Environmental Health Sciences. Maria has built a solid publication record in the area of environmental epidemiology, providing novel evidence for metals as a cardiovascular risk factors. Ongoing population-based studies which evaluate the potential role of epigenetics as a mediator of metal-related cardiovascular risk represent a clear next step to her investigations on metal toxicity at exposure levels that are relevant for the general population.