Nele Brusselaers
Universiteit Antwerpen, Antwerpen, BELGIUM
Karolinska Institutet, Stockholm, SWEDEN

Nele BRUSSELAERS is Associate Professor of Clinical Epidemiology at Karolinska Institutet in Stockholm (Sweden), where she is team leader of the epidemiology team at the Centre for Translational Microbiome Research (CTMR) and coordinator of the “Oncobiome” projects (microbiome and cancer). She also holds a fulltime Professorship at the Global Health Institute at Antwerp University, and is Guest Professor at Ghent University (both in Belgium). She completed her training as a medical doctor (2008), PhD (2010), master in infection control/hospital hygiene (2010) and first post-doc at Ghent University in Belgium; and moved to Sweden in 2012 where she lived until summer 2020 after which she moved back to Belgium. She also obtained a master in Epidemiology from the London School of Hygiene and Tropical Medicine (by distance learning, 2015).

Nele has extensive experience in clinical, cancer, microbiome and pharmaco-epidemiology by working with the Swedish nationwide health registries, several clinical (microbiome) cohorts and systematic reviews and meta-analyses, resulting in over 120 peer-reviewed articles. Nele has supervised 6 PhD students (9 ongoing) and 24 master students successfully, and teaches on graduate and post-graduate level, mainly on study design, epidemiology, systematic reviews, meta-analyses, microbiome etc.

Although she has a broad interest and experience in different clinical topics (incl. infectious diseases) with many international collaborations; her main focus is to investigate the long-term effects of commonly prescribed drugs on female health and early childhood, cancer and diseases of the gastro-intestinal tract, through potential drug-mediated alterations of the microbiome. Her overall aim is to contribute to optimizing clinical practice and long-term health– for which trans-disciplinary approaches and collaborations are increasingly required.

AbstractPopulation Variation of Microbiota

Technical advancements have accelerated microbiome research making it more affordable and feasible to perform large scale studies with thousands, or even hundreds of thousands of samples. Although size matters, proper study design remains crucial since humans and especially their microbiota are more diverse than a litter of new-born rodents or a series of patients. Where do we recruit our study participants? Who are they and how healthy are they? What do they eat, and which medications do they use? Which factors are affecting our microbiome compositions at different anatomical niches including our gastro-intestinal and reproductive tracts?

During this talk I will discuss what we already know about our microbiome during the different phases of life, in sickness and in health, and which scientific challenges still lie ahead. As an MD and clinical epidemiologist, I approach the microbiome field from a clinical and public health perspective – and how the microbiome can become useful as a tool in precision medicine, from prevention to diagnosis and treatment.

Jean-Louis Gueant
Lorraine University, Nancy, FRANCE

Jean-Louis Guéant, MD, DSc, is Professor of Medical Biochemistry-Molecular Biology at the University of Lorraine, Faculty of Medicine, Director of UMR-S Inserm 1256, Head of the Department of Biochemistry-Molecular Biology-Nutrition at the University Hospital of Nancy. He followed a MD, PhD double cursus at the Faculty of Medicine and the Faculty of Sciences of the University Henri Poincaré of Nancy, with the qualification in Hepato-Gastroenterology in 1984, and the degree of Doctor of Science in Nutrition in 1986. He is recruited as Master of Conferences – Hospitaller Practitioner in 1987 and appointed Professor of Universities – Hospital Practitioner in 1990. Prior to this appointment, he made several post doc stays at the State University of New York and the Institute Minerva of Helsinki (with R Gräsbeck as mentor). He then directs one of the 3 research teams of Inserm Unit 308 (director JP Nicolas) from 1988 and obtains the creation of an EP-CNRS team in 1996, which will become EMI-Inserm in 1999, then UMR-S Inserm 724 in 2002, UMR_S Inserm 954 in 2009 and UMR_S Inserm 1256. This Inserm Unit brings together nearly 70 people, including 3 Inserm researchers and 36 academic investigators in experimental and clinical research, around a research project on the interactions between nutrition, genes and the environment. In this context, he has been principal investigator of many national contracts. In hospital, he has contributed to the creation of the Reference Center for Rare Diseases of Metabolism in which he carries out a very specialized medical consultation on rare metabolic diseases with a regional, national and international recruitments of patients.

Kenneth Mandl
Harvard Medical School, Boston, USA

Ken Mandl directs the Computational Health Informatics Program at Boston Children’s Hospital and is the Donald A.B. Lindberg Professor of Pediatrics and Biomedical Informatics at Harvard Medical School. His work at the intersection of population and individual health has had a unique, sustained influence on the developing field of biomedical informatics. He was a pioneer of real time biosurveillance, tracking infections and detecting outbreaks with diverse data.  Cognizant of the limitations of extant electronic health record systems, Mandl developed a widely-adopted, highly influential approach (SMART)–substitutable apps that run universally on health IT systems. SMART lets innovators reach market scale and patients and doctors access an “app store for health.” Through the 21st Century Cures Act, SMART is now regulated as the standard interface by which patients, providers, and apps access data from electronic health records. He applies open source inventions to lead EHR research networks.  He leads Genomic Information Commons across eight leading children’s hospitals, participating in a federated model for genomic intelligence. Dr. Mandl is a member of the National Academy of Medicine, American Society for Clinical Investigation, Society for Pediatric Research, American College of Medical Informatics and American Pediatric Society. He is a recipient of the he Presidential Early Career Award for Scientists and Engineers, the Donald A.B. Lindberg Award for Innovation in Informatics.

Abstract Population Health and the Precision Medicine Ecosystem

Precision care for the individual requires multilevel insight into the biology, health, outcomes, and trajectories of populations. However, researchers and care delivery systems have faced nearly insurmountable barriers to permissioning and combining data from the care delivery system and research measurements. Mandl will discuss key underpinnings of an interoperable precision health ecosystem, affording access to broad population data.  Important features will be parsimonious standards, targeted governmental regulation, and federated models for sharing and collaboration.

Gaël Nicolas
Rouen University Hospital, Rouen, FRANCE

Gaël Nicolas is a neurogeneticist (MD in Neurology and PhD in Genetics) working as a professor and medical practitioner in Genetics in the University Hospital of Rouen (Department of Genetics and National Reference Center for Young Alzheimer Patients), the University of Rouen Normandie and the research unit Inserm 1245 (Rouen, France) with medical, research and teaching activities. His main medical activities include clinical diagnostics, genetic counseling and care of rare neurogenetic disorders as well as molecular genetic diagnostics. His research activity is centered on the genetics of neurological and psychiatric disorders with a specific focus on the genetics of Alzheimer disease, Primary Brain Calcification, and neurodevelopmental disorders. His research tools include exome and genome sequencing with diverse strategies including case-control association studies of rare variants. In early-onset Alzheimer disease, his main research findings include the identification of exome-wide significant enrichments of SORL1 rare variants, de novo mutations in sporadic cases, and oligogenic determinism. His main research aim is to make Alzheimer disease medical prevention possible thanks to the prediction of disease risk using personal genetic information.

Abstract Risk Prediction in Alzheimer Disease

Alzheimer disease (AD) is the leading cause of dementia with no clinically relevant disease-modifying cure. Biomarker, imaging and neuropsychological data obtained from presymptomatic carriers of rare mutations in exceptional autosomal dominant families suggest that the pathophysiological mechanisms of AD start years, if not decades, before the first symptoms. Accordingly, recent results of clinical trials suggest that AD prevention using antibodies targeting the main triggering factor of AD, i.e. Aβ peptide aggregation, might be efficient if delivered years after the first symptoms. Thus, predicting AD appears necessary to enable personalized AD prevention. Beyond rare autosomal dominant forms, AD is a complex disorder with a high genetic component. Deciphering the genetic determinants of AD etiology is hence necessary to detect individuals with a high risk. Large-scale case-control genetic studies recently identified a number of genes modulating AD risk. Among them, results from so-called rare variants identified in exome and genome sequencing data are associated with the highest levels of risk. I will present the genetic landscape of AD, from common variants to rare variants, and discuss on how we can build novel strategies to gather such heterogeneous information at the individual level, to make AD personalized prevention a reality in the future.

Jan Schildmann
Institute for History and Ethics of Medicine, Halle/Saale, GERMANY

Jan Schildmann is a specialist in internal medicine with additional qualification in palliative medicine and director of the Institute for History and Ethics of Medicine at the Martin-Luther-University Halle-Wittenberg. He has studied medicine in Berlin, London, Madrid and New York and holds postgraduate degrees in medical law and ethics and philosophy. In his research, he combines normative and empirical methods to explore ethical challenges in clinical practice and medical research. One focus of his work is the development, implementation and evaluation of ethical interventions in medicine. Next to research he is interested in teaching students and health professionals on various topics related to ethics and communication in medicine.

Abstract Precision Healthcare. Beyond medical data

Precision Medicine has focused on biological data. However, the current discussion as well as developments in precsision medicine miss an important point. This is to include non-biological data to realize the full potential of precision care.There is abundance evidence for the relevance of behavioural, psychological and social factors for health and healthcare. However, while the benefit of information on behaviours, social and further determinants for tailored health interventions has been taken up by scholars more recently, the debate still remains on a theoretical level. In addition, the methods and methodology of precision medicine have gained little attention outside genetics and biological medicine. To be able to realize the full potential of precision care we need empirical health care research to identify and characterise actionable non-biological determinants. Such basic research needs to be complemented by trials to determine the clinical benefits of tailored interventions. In this respect the lessons to be learnt from the last 20 years of precision medicine can inform health care research and pave the way to precise healthcare.

Harald Schmidt
Maastricht University, Masstricht, NETHERLANDS

With a double degree in Medicine and Pharmacy, Harald Schmidt has a passion for network and systems medicine to re-define what we call “disease” from a descriptive symptom- and organ-based to a mechanism-based approach by using big data, innovative target validation, new mechanism-based diagnostics and rapid repurposing of registered drugs for new clinical applications by network pharmacology. He performs high risk/high potential gain research in areas of major medical need, such as the development and commercialisation of a first-in-class neuro-protective therapy in stroke, a therapy against a common and yet untreatable form of heart failure, and a therapy for resistant hypertension. He chaired the COST action OpenMultiMed on network and systems medicine, coordinates the H2020 project REPO-TRIAL on in-silico network pharmacology, leads the clinical work package in the H2020 programme FeatureCloud. From 2012-2017 he was awarded an ERC AdG, thereafter an ERC PoC grant. Together with Jan Baumbach he is co-editor-in-chief of the 2018 founded journal Systems Medicine and has founded the International Network Medicine Association (INMA.org). His multi-national (Germany, USA, Australia, Netherlands) research experience in Academia, Industry (Abbott) and Biotech (Vasopharm) has led to high impact publications (Hirsch 89) with high socio-economic relevance such as drug and diagnostics patents, spin-offs and patient benefit.

Abstract The End of Medicine as we Know it

Existing drugs often fail to provide relevant benefit for most patients. The efficacy of the discovery of new drugs is low and in a constant decline predicting that pharma’s current approach may by the end of the 20’s no longer be financially sustainable. Also, why should we eternally need to discover new drugs. This poor translational success rate of biomedical research is due to lack of study quality and reproducibility and publication focus and bias. The most important reason, however, is our current concept of disease, i.e. mostly by organ or symptom, not by mechanism. Network Medicine will lead to a mechanism-based redefinition of disease, thereby enabling precision diagnosis and therapy. Due to drug repurposing this may eventually eliminate in many cases the need for drug discovery. Successful clinical drug repurposing will in turn also provide the necessary proof-of-concept for network medicine in general. If successful, we will need to reorganization of how we teach, train and practice medicine, moving from current organ-based disciplines, specializations and clinics and moving towards interdisciplinary board like structures. Examples of this new approach to disease include the redefinition of several cancers, immune diseases and a cluster of cerebro-cardio-metabolic phenotypes according their underlying molecular mechanism, including examples for drug repurposing and mechanism-based diagnostics. Importantly, a molecular disease mechanism is not a single protein, as currently often linked to common disease therapeutics, but always a signaling network. We observe however, that these networks in many cases differ from current signaling networks, which are rather mind maps of proteins assumed to function in a similar manner or use similar messengers. With respect to disease modules these networks are often smaller, overlap and thus lead to different drug repurposing decisions. Finally, since these mechanisms are networks, optimal therapy is a combination of drugs targeting several molecules within the same module in a synergistic manner. This allows low dosing and reduce the risk of any potential side effects. Finally, diagnostics are essential, in order to match patients that present both the phenotype and mechanotype and thus make therapies reach numbers needed to treat close to 1, i.e. that work in every patient. Since 80% of all proteins are present in all cells, the likelihood that a necessary pathway can be detected in (rare) circulating blood cells is proving a readily accessible platform to test module dysfunction, which we term the stimulome assay and which can also be considered an ex vivo efficacy test for the drugs to be clinically repurposed.

Y. Shrike Zhang
Harvard Medical School, Cambridge, USA

Dr. Zhang is an Assistant Professor in the Department of Medicine at Harvard Medical School and Associate Bioengineer in the Division of Engineering in Medicine at the Brigham and Women’s Hospital. Dr. Zhang is directing the Laboratory of Engineered Living Systems, where the research is focused on innovating medical engineering technologies, including 3D bioprinting, organs-on-chips, microfluidics, and bioanalysis, to recreate functional tissues and their biomimetic models for applications in regenerative medicine and personalized medicine. He is an author of >185 peer-reviewed publications (h-index: 52) and his scientific contributions have been recognized by >40 international, national, and regional awards.

Abstract Tissue engineering and 3D printing for regenerative therapy

Over the last decades, the fabrication of three-dimensional (3D) tissues has become commonplace. However, conventional 3D fabrication techniques are limited in their capacity to produce complex tissue constructs with the required precision and controllability that is needed to replicate biologically relevant tissues. To this end, 3D bioprinting offers great versatility in the fabrication of biomimetic volumetric tissues that are structurally and functionally relevant. It enables precise control of the composition, spatial distribution, and architecture of bioprinted constructs facilitating the recapitulation of the delicate shapes and structures of targeted organs and tissues. This talk will discuss our recent efforts in developing a series of advanced 3D bioprinting strategies along with various cytocompatible bioink formulations. These platform technologies are likely to provide new opportunities in constructing functional tissues to facilitate regeneration and microtissue models for promoting personalized medicine.