CONFERENCE KEYNOTE SPEAKERS

Wolfgang Oertel

Prof. Dr. Wolfgang Oertel is a clinical neurologist at the Philipps University Marburg. Since receiving his certification of Neurology in 1986, Prof. Oertel has been part of advisory boards, scientific societies and international institutions. He is (co-)founder of the German Brain Bank for Neurodegenerative Diseases, the “German Competence Network Parkinson Syndromes”, the “German PD clinical trial network (German Parkinson Study Group)”,  the “International REM-Sleep Behavior Disorder (RBD) Study Group” (IRBDSG) and the German RBD Study Group (GRBDSG). He is the recipient of many prestigious scientific awards, with the latest being the Life Time Achievement Award from the European Federation of Neurological Associations (EFNA) which he received in 2018. His scientific profile (h-factor 100) is translational research from molecular experimental research to clinical studies. Since 2005 his group focusses in experimental and clinical research on the prodromal stages of Parkinson’s disease with a special interest on REM-Sleep Behaviour Disorder (RBD).

For more Information:

Link 1

Link 2

Neuroprotective therapy in prodromal Parkinson disease - illusion or justified hope?

Alpha-synucleinopathies (ASYN) represent – after Alzheimer dementia – the second largest group of progressive neurodegenerative disorders. ASYN subsume Parkinson’s disease (PD), dementia with Lewy bodies (DLB ) and the rare Multiple System Atrophy (MSA). These disorders share  the pathological aggregation of the protein alpha-synuclein in neurons (PD, DLB) or oligodendrocytes (MSA) and the prodromal phenotype „REM sleep behaviour disorder (RBD)“. Presently available treatment is symptomatic with the focus on dopamine replacement pharmacotherapy. In 1996 a mutation of the SNCA gene coding for alpha-synuclein was discovered as the cause of autosomal-dominant PD. In 1997 the Lewy bodies, one of the neuropathological hallmarks of PD, were found to contain aggregated alpha-synuclein. In 2003 Braak published his PD staging hypothesis, that aggregated alpha-synuclein initially develops in the periphery (olfactory bulb, gastrointestinal system) and caudo-rostrally advances via the dorsal motor nucleus of the vagal nerve and the locus coeruleus to finally reach and lesion the dopaminergic substantia nigra.  At this stage the PD-motor symptom bradykinesia becomes clinically manifest. After 20 years of research on treatment strategies targeting aggregated alpha-synuclein clinical trials in early PD patients are under way to test the neuroprotective potential of „anti-alpha-synuclein“ drugs: they include – besides others – antisense-oligonucleotides, active and passive immunisation and small molecules which resolve alpha-synuclein aggregates in PD animal models. After summarizing the available results of these clinical trials the question will be discussed whether it will be possible to conduct studies in the prodromal stage of ASYN. As an example for such a prodromal ASYN stage the parasomnia RBD is selected and the search for prodromal biomarkers and prodromal progression markers in RBD will be detailled. The later are an essential prerequisite for a future neuroprotection trial in prodromal ASYN.

Multi-Omics of Drug Sensitivity of Blood Cancers

I will use the opportunity of this talk two present two topics, one statistical-methodological and one an application of multi-omics machine learning to precision medicine of blood cancers.

Part 1 will reconsider one of the most pervasive components of genome scale data analysis, multiple testing. I will discuss how the use of side-information in a statistical principled manner by “Independent Hypothesis Weighting” can improve the power and quality of analyses at essentially no cost.

In Part 2, I will give an overview over Multi-Omics-Factor Analysis and how it can be used to discover novel, biologically and clinically relevant disease stratifications, on the example of high-throughput ex-vivo drug response assays and multi-omics characterization of blood cancers.

Microbiota-centered Interventions: data and prospects

In oncology, a novel therapeutic era based on immune checkpoint blocades (ICB) targeting CTLA-4 or PD-1 has come of age. Seventy percent of patients will eventually progress however and drug- induced autoimmune toxiciteis are frequent. Therefore, predictors of clinical benefit and strategies to safely enhance ICB efficacy are urgentely needed. Multiple lines of evidence have shown that concentional chemotherapy, allogenic transplantation and immune-based therapies (IL-10R, CTLA_4 and anti-PD_1 blockades) rely upon the composion of the gut microbiota to exert their bioactivity. Antibiotics blunt the efficacy of ICB, and fecal microbial transplantation (FMT) may restore responsiveness of ICB-resistant melanoma. It is timely to discuss how and why antibiotics compromise the efficacy of cancer immunotherapy, describe the balance between beneficial and harmful microbial species in play during therapies, and introduce the potential for microbiota-centered interventions for the future of immuno-oncology.

Francesco Iorio

The Iorio Group

The Iorio Group works at the interface of biology, machine learning, statistics and information theory with the goal of understanding and predicting how genomic alterations and molecular traits from other omics contribute to pathological processes, biological circuits’ rewiring and have an impact on therapeutic response in human cancers and other diseases.

Cancer DepMap Analytics at Wellcome Sanger Institute

CRISPR-cas9 screens and multi-omic data integration for identifying new oncology therapeutic targets

I will introduce a number of computational analyses focusing on data from large scale genetic-perturbation/drug screens performed across panels of hundreds of cancer in-vitro models and their integration with the multi-omic characterisation of these models, and data from public cancer genomics repositories. The aim of these analyses is to identify, respectively, new oncology therapeutic biomarkers, new therapeutic targets, drug repositioning opportunities and new somatic variants of clinical relevance.
I will present results and methods designed and implemented by my research team, as well as I will discuss related computational challenges and possible ways to tackle them.

Interesting links:
Human Technopole
Wellcome Sanger Insitute

Lindsay Hall

Prof. Dr. Lindsay is the Chair of Intestinal Microbiome at the TU München since 2020. She also holds a Group Leader position at the Quadram Institute, UK and is a Wellcome Trust Investigator. Her lab’s research focus involves defining microbe and host interactions, with a focus on diet and nutrition.  She obtained a BSc in Microbiology from the University of Glasgow, a PhD in Microbiology and Immunology from the University of Cambridge (Wellcome Trust Sanger Institute), and was a postdoctoral fellow at University College Cork, Ireland (APC Microbiome Institute). She returned to the UK to take up a Senior Lectureship at the University of East Anglia before moving to Quadram end of 2015.

Exploring the delicate balance of the very early life gut microbiota

Initial colonisation of the gut by pioneer bacterial species is the first key step for host well-being. The process of initial gut microbiota colonisation in preterm babies is radically interrupted due to a variety of factors including mode of delivery and antibiotics. This aberrant colonisation of premature infants appears pivotal to the development of a number of diseases, including necrotising enterocolitis (NEC), which is linked to overgrowth of opportunistic pathogens. Importantly modulation of the preterm microbiota may aid in prevention of NEC in preterm infants. I will discuss how Bifidobacterium supplementation represents a powerful opportunity for strategically manipulating the wider early life microbiota when bacterial assembly is disturbed within the context of preterm birth. I will also touch on new approaches for rapid preterm microbiota profiling and underlying properties of pathogenic NEC-associated bacteria.

LIH LECTURE SERIES

Caroline Roberts

Caroline Robert, M.D., Ph.D. did her MD training at the Paris V University Medicine School, France and completed a research fellowship at Harvard, Brigham & Women’s hospital, Boston MA, USA in Cancer Immunology and Immunotherapy. She is presently Head of the Dermatology Service at Gustave Roussy Cancer Campus and co-director of the Melanoma Research Unit at INSERM 981 Paris-Sud University. She is full Professor of Dermatology and responsible for teaching Dermatology and Dermato-Oncology in Paris-Saclay University Medicine School. Her main interests are clinical and translational Research on Melanoma involving immunotherapy and targeted therapy. She is national and international coordinator of many clinical trials from phase I to III dedicated to patients with melanoma and other skin cancers. Her research work focuses on the involvement of the control of mRNA translation in resistance to cancer therapies. The objectives are the identification of new predictive biomarkers as well as the development of new therapies to delay therapeutic resistance. She has authored more than 350 articles in peer-reviewed scientific journals, including a number of publications on new treatments for metastatic melanoma. She is a member of the editorial board of Cell. She and past-president the Melanoma group of the EORTC and is board member of several European and US cooperative groups: EADO, ESMO, EADV, ASCO and AACR. She has received several awards and prizes including the French Legion d’Honneur in 2014, the Estela Medrano Award for the Society for Melanoma Research in 2018, the ESMO Woman Award in 2020. She was elected as a corresponding member of the French National Academy of Medicine in 2019

Role of mRNA Translation in Melanoma Biology and Therapeutics

Therapeutic progress in metastatic melanoma have been the fastest among all cancers in the last ten years thanks to the demonstration of efficacy of immunotherapy targeting immune checkpoints CTLA-4 and PD1. The median survival of patients has more than doubled and some patients are definitely cured. These new strategy has quickly gone beyond the field of melanoma and is now used successfully against many other cancers.However, these revolutionary treatments are not effective in every patients, and resistance appears either immediately (i.e. primary resistance) or after an initial benefit of the treatment (secondary resistance). Many of these resistance mechanisms, genetic or epigenetic, have been described, but they are far from being fully elucidated. Our main challenges today are to unravel these resistance mechanisms in order delay or circumvent them. We demonstrated that the protein complex involved in the control of translation initiation, eIF4F, plays a critical part in resistance to targeted agent as well as in PDL1 expression. We have continued to explore the relationship between the control of protein translation and immunoreceptor expression.Our recent data shows that additional immunoreceptors are also controlled by eIF4F and could be targeted by inhibitors of this complex. Our goal is to unravel the dynamics of immumnoreceptors mRNAs translation, both on cancer cells and on cells of the microenvironment, during the course of the immune response using mice models and sequential biopsies of patients treated with immune checkpoint inhibitors.These results offer promising perspectives for the identification of biomarkers of efficacy and resistance as well as for the development of new therapeutic strategies based on translation inhibitors in combination with standard cancer treatments.