Message from the Board

Despite the socio-economic and health tumult caused by the COVID-19 pandemic, 2020 was the year LIH could prove its reputation as a truly translational institute and as a leader in clinical research, not just nationally but internationally, thereby contributing to upholding Luxembourg’s standing as the hotbed for disease management.

The rapid mobilisation of the Luxembourgish government and of the various research institutes from the very start of the COVID-19 pandemic, as well as the seamless collaboration between all local players, contributed substantially to the protection of public health and the containment of the spread of the disease among the Luxembourg population. Indeed, the prompt establishment of a dedicated taskforce to coordinate all national efforts and the ensuing implementation of several unique research and public health initiatives won the Grand Duchy an unprecedented visibility at the international level as a leading centre of excellence in translational and clinical research. In this context, LIH acted as a central pillar for the fight against COVID-19.

Through its leading position within the national COVID-19 Taskforce and the remarkable work of its staff, LIH set up and coordinated two cohort studies to assess the severity of COVID-19 and its prevalence among the population, focusing particularly on the role of asymptomatic carriers, as well as participating in a European clinical trial aiming to assess the efficacy and safety of novel antiviral treatments. In addition, the institute coordinated a unique and unparalleled nationwide large-scale screening campaign, with the goal of identifying positive cases and breaking infection chains early on. Several LIH scientists also received significant financial support for their innovative COVID-19-related research projects through a novel dedicated funding programme launched by the Luxembourg National Research Fund (FNR).

These achievements relied on the close cooperation between LIH and all relevant local and international partners, as well as on effective and tailored communication support campaigns, making the national response to the pandemic a real illustration of a “Made in Luxembourg” success.

Of course, none of said achievements could have been possible without the passion and dedication of the entire LIH staff, from research to administration, and without the enlightened leadership and mentoring of the management. I therefore take this opportunity to extend my warmest gratitude to the people behind the excellence of LIH. On behalf of the entire Board of Directors, Villmols Merci!

COVID-19: A COLLABORATIVE PRIORITY AREA FOR LUXEMBOURG AND LIH

Research Luxembourg launches the “COVID-19 Taskforce”

As a first response to the COVID-19 pandemic, Research Luxembourg, a joint initiative of all the main players in Luxembourg's public research sector, set up a dedicated COVID-19 Taskforce in March 2020, with LIH’s CEO Prof Ulf Nehrbass as spokesperson and Prof Paul Wilmes (University of Luxembourg, LCSB) as deputy spokesperson. The aim of the Research Luxembourg COVID-19 Taskforce was to help address the emergency by mobilising the knowledge, human and material resources of the Luxembourg public research sector and offering the national healthcare system the combined expertise available within the Research Luxembourg member institutes – namely LIH, the Luxembourg Institute of Socio-Economic Research (LISER), the Luxembourg Institute of Science and Technology (LIST), the Laboratoire National de Santé (LNS), the University of Luxembourg, Luxinnovation and the Luxembourg National Research Fund (FNR) – under the coordination of the Ministry of Higher Education and Research (MESR).

Specifically, the three main missions of the Taskforce were to coordinate the provision of support from the national research community to healthcare providers; help identify and centralise a variety of priority activities, leveraging on the inter-sectoral expertise in molecular biology, epidemiology, clinical trials and fundamental research; and acting as the central point of contact between the national research ecosystem, the clinical community and the authorities. From an operational perspective, the Taskforce focused on three main pillars, namely the implementation of a nationwide prevalence study to assess the extent of the spread of the virus and the number of asymptomatic individuals; a stratification study to identify risk factors that contribute negatively to disease progression; and statistical simulations on the evolution, impact and spread of the COVID-19 pandemic to provide short- and medium-term projections and thus facilitate decision-making on when restrictions could be lifted. These priority pillars resulted in the prompt setup of several national projects and initiatives, which gained international visibility for their seamless and rigorous organisation and for the high quality of the research work carried out.

Testing asymptomatic individuals to assess COVID-19 spread in Luxembourg: the CON-VINCE study

The first study launched under the aegis of the Research Luxembourg COVID-19 Taskforce to help contain the pandemic was CON-VINCE (COvid-19 National survey for assessing VIral spread by Non-affected CarriErs), which kicked off in April 2020. Under the leadership of Prof Rejko Krüger, Director of Transversal Translational Medicine (TTM) at LIH, the project aims to evaluate the dynamics of the spread of the COVID-19 disease, with a specific interest in the asymptomatic and oligosymptomatic individuals, within the Luxembourgish population by testing a representative panel of over 1,800 people for the presence of the SARS-CoV-2 virus. The CON-VINCE participants are followed up over a period of 12 months. Asymptomatic individuals – referred to as ‘silent carriers’ – and mildly symptomatic carriers play a significant role in the spread of the virus, although they often remain undetected, thereby making CON-VINCE a key pillar in the characterisation of the nature, prevalence and transmission modality of COVID-19 in the Grand Duchy.

Predicting the severity of COVID-19 infection: the Predi-COVID study

A second flagship project of the Research Luxembourg COVID-19 Task Force is Predi-COVID, a cohort study launched in April 2020 and coordinated by the LIH Department of Population Health (DoPH). Predi-COVID (Luxembourg cohort of positive patients for COVID-19: a stratification study to predict severe prognosis) aims to define which patient profiles can be associated with a more severe disease prognosis. Specifically, Predi-COVID focuses on the identification of the clinical, epidemiological and socio-demographic characteristics, as well as specific biomarkers from both the SARS CoV-2 virus and the patient, which can help predict the way the disease will evolve in a given individual, according notably to his immune profile. The study will thus contribute to a better understanding of the heterogeneity observed in disease severity and prognosis and of the long-term health consequences of COVID-19, ultimately enabling the accurate evaluation of patients infected with SARS-CoV-2 and more personalised care recommendations.

Assessing the safety and efficacy of potential COVID-19 treatments: the DisCoVeRy clinical trial

In addition to the efforts related to the characterisation of COVID-19, LIH has also been involved in studies seeking to identify treatment options for this novel disease. Thus, in March 2020, the Clinical and Epidemiological Investigation Centre (CIEC) of the LIH Department of Population Health (DoPH), the National Infectious Disease Department (Service National des Maladies Infectieuses – SNMI) and the Intensive Care Unit of the Centre Hospitalier de Luxembourg (CHL) and the Hôpitaux Robert Schuman (HRS) joined the consortium of the European clinical trial ‘DisCoVeRy’, coordinated by the French National Institute of Health and Medical Research (Inserm) and financially supported by the EU projects COMBACTE, PREPARE and RECOVER. The study, part of the international ‘Solidarity’ trial led under the auspices of the World Health Organization (WHO), aimed to test the efficacy and safety of four experimental repurposed antiviral therapies — remdesivir, lopinavir/ritonavir, interferon beta and hydroxychloroquine — in hospitalised COVID-19 patients.

Supporting Luxembourg’s diagnostic capacity and large-scale testing strategies

As part of the many initiatives of the Research Luxembourg COVID-19 Taskforce, Prof Markus Ollert, Director of the LIH Department of Infection and Immunity (DII), has been leading a work package dedicated to creating additional diagnostic capacity at LIH, with the goal of supporting studies such as CON-VINCE and Predi-COVID, but also Luxembourg’s healthcare providers and diagnostic laboratories in testing and diagnosing the growing number of potentially infected patients. The first activity in the work package, under the coordination of Dr Chantal Snoeck of the DII Clinical and Applied Virology group, entailed the setup of a diagnostic research lab at LIH where virologists and volunteers have been working in collaboration with other Luxembourgish partners on developing a novel and extremely sensitive PCR assay to screen patient samples for SARS-CoV-2. A second activity entailed the validation and testing of a serological immunoassay to detect and measure the presence of antibodies against the virus in the blood, as well as the recombinant expression and production of antigens from SARS-CoV-2. This aspect relied on the interdisciplinary expertise of several DII team members, including Dr Christiane Hilger and Dr Annette Kühn from the Molecular and Translational Allergology research group, Dr Andy Chevigné from the Immuno-Pharmacology and Interactomics group and Dr Judith Hübschen from the Clinical and Applied Virology group. A third activity of the work package, directed by Dr Danielle Perez–Bercoff, consisted in verifying whether serum containing anti-SARS-CoV-2 antibodies can effectively neutralise the virus, in order to develop a virus neutralisation test. Finally, the DII team aimed to test a selection of drugs commonly used for other diseases on the specific SARS-CoV-2 virus present in a given patient, so as to observe which therapeutic molecule the virus responds to and therefore provide doctors with a personalised treatment plan for each individual patient. This personalised antiviral profiling task is coordinated by Dr Carole Devaux, leader of the HIV Clinical and Translational Research group. This entire work package also benefited from the support of DII scientists Dr Cathy Leonard, from the Allergy and Clinical Immunology Group, and Erica Grant, PhD candidate in the Eco-Immunology and Microbiome Group.

Enabling evidence-based decision making in Luxembourg

LIH has been contributing to another key work package of the Research Luxembourg COVID-19 Taskforce, namely the provision of evidence-based advice on the novel coronavirus to the Luxembourg government and other relevant stakeholders. This work package was led by Prof Dirk Brenner, Deputy Head of Research & Strategy and Head of the Experimental and Molecular Immunology research group at the LIH Department of Infection and Immunity (DII). Specifically, the team responded to COVID-19-related requests from the government and from other implicated stakeholders. They provided advice, suggested concrete solutions and prepared strategic decisions. For instance, in the context of the work package, the LIH team supported the Research Luxembourg COVID-19 Taskforce in defining an appropriate exit strategy following the lifting of the restrictions in May 2020. In addition, the team performed an ongoing literature review for the Ministry of Health and set up a selected scientific literature feed in order to keep the scientific and healthcare community up to date on the latest developments in the field.

A unique “Large Scale Testing” campaign as the pillar of the deconfinement strategy

As part of the national exit strategy, the Research Luxembourg COVID-19 Taskforce, in close cooperation with the Ministry of Higher Education and Research and the Ministry of Health, implemented a unique nationwide “Large Scale Testing” (LST) campaign, encouraging residents and cross-border workers to voluntarily get tested for COVID-19 through a PCR test on a throat swab. With a testing capacity of up to 20,000 PCR tests per day, this unprecedented public health initiative aimed to break infection chains as early as possible – detecting for the first time asymptomatic individuals which were estimated to account for up to 80% of cases – thereby containing the spread of the virus and enabling a safer and speedier lifting of the lockdown restrictions.

FNR COVID-19 Fast Track Call: 12 LIH projects shortlisted and funded

In April 2020, the Luxembourg National Research Fund (FNR) launched the novel COVID-19 Fast Track Call funding programme in the framework of the Research Luxembourg Task Force work packages. The COVID-19 Fast Track Call aims to (co-)support short-term research projects on COVID-19, to accelerate the understanding and treatment of the disease, as well as addressing the legal, socio-economic and infrastructural aspects associated with the pandemic. Following the first deadline of the call on April 14th, eight LIH projects from the Quantitative Biology Unit (QBU), the Department of Population Health (DoPH) and the Department of Infection and Immunity (DII) were shortlisted and funded, for total financial support amounting to almost EUR 416,000. These aim to investigate multiple aspects of the COVID-19 infection, from tissue damage, microbiome alterations and disease severity, to immunity, virus neutralisation and epidemiology.

An additional 4 projects from the Department of Oncology (DONC), DII and QBU were selected for funding under the second call of the programme in May 2020, for total support amounting to over EUR 197,000. These will investigate multiple aspects of the COVID-19 infection, from serological profiling and PCR testing, to novel antiviral therapies and vaccines.

#LIHTellMeWhy: explaining COVID-19 to children!

In addition to supporting the communication efforts of the COVID-19 Taskforce tailored to scientific and adult audiences, the LIH Communication team implemented a communication campaign dedicated specifically to children. Launched in March 2020, #LIHTellMeWhy is an original collection of ten catchy digital cartoons providing simplified details on ongoing COVID-19 research and developments to kids between the ages of four and eight. This LIH initiative aims to support parents in explaining a very delicate situation to their little ones, ensuring they receive a level of information that is adjusted to their age and vision of the world. Indeed, aside from carrying out complex research in high-security labs, the LIH staff also seeks to inspire the younger generations and arouse their interest in biomedical sciences. This is in line with one of the missions of the Institute, namely finding approachable and understandable ways of communicating its activities to lay audiences, making complex topics more easily comprehensible and therefore raising awareness on Luxembourg’s research efforts among the general public.

Each of the ten cartoons, published on a weekly basis between March and June 2020, addresses a specific question submitted by children or their parents in a fun, entertaining and accurate way. The questions covered by the ten cartoons include the definition of a virus, what steps can be taken to avoid getting sick and what the virus ‘eats’, among many others.

The cartoons are available on the dedicated section of the LIH website in four languages (English, French, German and Luxembourgish).

‘Large Scale Communication’ for the Large Scale Testing: the #AAAH campaign

A nationwide initiative such as the Large Scale Testing (LST) − the success of which depends largely on the adhesion and buy-in of the population – requires a highly effective nationwide communication support, encouraging as many people as possible to get tested and overcoming any reticence and unwillingness to participate. To this end, as part of the first phase of the LST, LIH set up a comprehensive communication campaign, supported by external providers and the COVID-19 Taskforce, covering all key national and international media. The first stage of this communication campaign, implemented in parallel to the launch of the LST, consisted in the production and dissemination of flyers, animations on social networks and radio spots broadcast on all major national stations (L'Essentiel, RTL Radio and Eldoradio), to provide information and practical details on the LST.

The second stage of the communication plan consisted in the so-called ‘#AAAH campaign’, which ran between June 2020 and September 2020. The idea behind this original concept was to give additional visibility to the LST and raise awareness of its benefits, both for each individual as well as for society as a whole, in a friendly, relaxed, straight-to-the-point and visual way, particularly as the summer holidays approached. The #AAAH campaign, developed by LIH with the support of an external agency, entailed the shooting of a funny video consisting of a series of open mouths saying “AAAH”, alternating with larger frames showing local celebrities all saying “AAAH”. The celebrities then get tested to show how easy and quick the procedure is and how getting tested could contribute to a safer lockdown exit and a more relaxed summer. This multilingual campaign (in Luxembourgish, German, French, English and Portuguese) was disseminated locally and internationally to cross-border workers. It was also transmitted as a radio and TV spot on national and Greater Region radio stations and shared on multiple channels via an extensive media plan, including on social media, online (e.g. through bannering and Search Engine Marketing) and in print formats in the media and in public places (e.g. buses and bus stops).

This second phase was then followed by the third and final stage of the communication campaign, which consisted in a more educational and informative animation aiming to act as a transition between the end of the first phase of the LST and the beginning of the second. The #AAAH campaign was very well received by the public and reached its objective of raising awareness of the LST nationally and internationally. Indeed, between June 2020 and September 2020, the 121 posts, tweets, videos and ads published on social media to advertise the LST received 6.5 million impressions (views) and generated over 200,000 engagements (reactions, clicks, shares, comments). All in all, after the start of the campaign, over 10,000 test bookings per day were recorded in July 2020, helping keep the pandemic under control during the summer. As a result, Luxembourg was considered to be the global leader in mass screening in August 2020.

INTERNATIONAL EXCELLENCE

Advancing translational research beyond borders

The excellence and reputation of LIH and IBBL (Integrated Biobank of Luxembourg) as valuable partners for European-funded projects was further confirmed in 2020. Indeed, the two institutes joined the consortia of six highly competitive European studies, which kicked off in 2020. Moreover, several LIH scientists obtained financial support from a prestigious funding scheme of the European Commission for their innovative and high-potential research projects. These contracts and grants span a variety of priority areas for LIH and IBBL, including the use of digital technologies and Artificial Intelligence to improve cancer therapies, the advancement of translational research and, importantly, the improvement of COVID-19 diagnosis, treatment and pandemic preparedness. Participation in these projects consolidates LIH and IBBL collaborations with leading international partners and further contributes to strengthening the visibility of the institutes, and of Luxembourg’s biomedical research ecosystem in general, as an international centre of excellence in translational and transversal medicine.

// REVERT: artificial intelligence to fight colorectal cancer

Through its biobank IBBL, LIH joined the consortium of REVERT (TaRgeted thErapy for adVanced colorEctal canceR paTients). This four-year project, coordinated by the San Raffaele Scientific Institute for Research and Healthcare, is a collaboration between 14 partners from six European countries and is funded under the European Commission’s Horizon 2020 programme. REVERT, which kicked off in January 2020, aims to leverage artificial intelligence (AI) to identify a predictive algorithm to be used in the treatment of patients with advanced colorectal cancer (CRC). Over 400,000 people are diagnosed annually with CRC in Europe, and almost half end up developing distant metastases. Despite the ability of drugs such as bevacizumab, cetuximab and panitumumab to significantly improve median survival in patients with unresectable metastatic CRC, their efficacy depends on a patient’s clinical characteristics and disease biology. Moreover, side effects and considerable costs constitute additional downsides. In this context, REVERT aims to understand the specific pathophysiology of metastatic CRC (mCRC) in patients responding well or poorly to therapies, in order to design an optimal strategy for the treatment of mCRC on a case by case basis, with therapeutic interventions tailored to patient’s particular features. Specifically, the consortium seeks to create an innovative decision support algorithm based on AI techniques and real-world data generated by several European hospitals, which will ultimately be able to

// EATRIS-Plus: supporting translational medicine through capacity building

Personalised medicine relies on the identification of reliable biomarkers to evaluate the likelihood of developing a disease, diagnose a disorder, assess its severity and progression, and determine the most accurate treatment strategies. However, the road to biomarker validation before their effective application in the clinical context is complex. To assist scientists in the challenging phase of translating research results into tangible medical applications, the European Infrastructure for Translational Medicine (EATRIS) was set up in 2014. As a research infrastructure, EATRIS provides access to laboratory, clinical, industrial, legal and regulatory expertise, technology and services to academia, industry and patient associations, in order to help researchers decrease the risk associated to the early stages of drug or biomarker development. Building on the success of the EATRIS initiative, the EATRIS-Plus project, which kicked off in January 2020, aims to further expand the infrastructure’s service offering, expertise, technologies and capacity so as to keep addressing research needs in personalised and translational medicine. Specifically, over its 4-year duration, EATRIS-Plus seeks to consolidate EATRIS capacities to better serve academia and industry; further strengthen the long-term sustainability of the EATRIS financial model; drive patient empowerment through active involvement in the infrastructure’s operations; and expand strategic partnerships with RIs and other relevant stakeholders. As part of the project’s consortium and under the coordination of IBBL project manager Sabrina Saracino, IBBL will be leading a specific task focused on the implementation of an inter-laboratory performance assessment for biospecimen processing, owing to its renowned expertise in the development of proficiency testing (PT) schemes. This aims to ensure that samples are fit for the purpose of downstream “omics” analyses and will allow the comparison of processing performance between laboratories. EATRIS-Plus boasts a highly interdisciplinary consortium of 19 partners from academia, industry and patient organisations from 16 European countries. It is funded through the Horizon 2020 programme of the European Commission.

// “Marie Sklodowska-Curie Individual Fellowships” for LIH researchers

Drs Amela Jusic, from the LIH Department of Population Health (DoPH), Marie Boudaud and Tomasz Uchanski, from the LIH Department of Infection and Immunity (DII), were awarded financial support in the framework of the European Commission’s “Marie Sklodowska-Curie Individual Fellowships” (MSCA IF) funding scheme in February 2020. The programme will back the scientists’ work on hypertension, receptor-chemokine interactions and Inflammatory Bowel Diseases (IBD). Specifically, Amela Jusic, postdoctoral fellow in the DoPH Cardiovascular Research Unit led by Dr Yvan Devaux, will investigate the function and biomarker potential of mitochondrial microRNAs in hypertension under the “MITO” project, with the goal of discovering novel methods to improve health outcomes in hypertension patients. The MSCA IF will also support Tomasz Uchanski, postdoctoral fellow in the DII Immuno-Pharmacology and Interactomics Research Group under the supervision of Dr Andy Chevigne, in advancing the structural and functional analysis of chemokines through his project “Novel tools for structural insight into receptor-chemokine complexes”. Finally, Marie Boudaud, postdoctoral fellow working in the DII Eco-Immunology and Microbiome Research Group under the supervision of Dr Mahesh Desai, was awarded the MSCA IF for her project “Mucobiome-mediated immune pathways in Inflammatory Bowel Diseases” (MUCO-IMMUN). Under this study, she will investigate the mechanisms by which the mucobiome – i.e. the microbial communities living in the human gastrointestinal tract that can digest the intestinal mucus layer – activates specific disease-promoting immune pathways under low dietary fibre conditions, a factor which is believed to play an important role in IBD pathogenesis.

// MIRABANK: a bank of multi-resistant bacterial strains in Luxembourg

In July 2020, the Laboratoire national de santé (LNS) and IBBL launched MIRABANK, a joint project on behalf of the European Centre for Disease Prevention and Control (ECDC) based on the creation of a bank of multi-resistant bacterial strains in Luxembourg. Under the coordination and responsibility of IBBL Project Manager Dr Kristin Kornerup, the biobank will collect bacterial strains – which are a new type of sample for the institute – resistant to carbapenems and/or colistin antibiotics, as well as temporarily storing them prior to analysis. The LNS, for its part, will be responsible for confirming the identification of the strains. Specifically, IBBL will receive some 4,000 strains from 37 European countries, which will be forwarded to the Bacteriology, Mycology, Antibiotic Resistance and Hospital Hygiene Unit of the LNS Microbiology Department, before returning to IBBL for freezing, storage and shipment to a genomic analysis laboratory. The first strains integrated into MIRABANK in July 2020 were the strains from Luxembourg, collected owing to the participation of the country’s four hospitals. The project will significantly contribute to the fight against resistance to antibiotics of last resort, a phenomenon that has particularly increased in Europe in recent years.

// ‘ERAvsCORONA Action Plan’: three LIH COVID-19 projects funded

The European Commission confirmed its support to three new research projects involving LIH, submitted within the framework of the Horizon 2020 call “Innovative and rapid health-related approaches to respond to COVID-19 and to deliver quick results for society for a higher level of preparedness of health systems” as part of the Horizon 2020 ERAvsCORONA Action Plan. The total funding for the three studies amounts to EUR 26.2 million.

Specifically, LIH, through the Cardiovascular Research Unit (CVRU) of its Department of Population Health (DoPH), will be coordinating “COVIRNA” (A diagnostic test to improve surveillance and care of COVID-19 patients). Led by Dr Yvan Devaux, CVRU Group Leader, COVIRNA is a 24-month patient-centred Innovation Action (IA) aiming to generate a diagnostic tool to identify COVID-19 patients at risk of developing fatal cardiovascular complications, ultimately leading to their improved surveillance and care. The project, which boasts a complementary consortium of 15 partners from healthcare, academia and industry from 12 European countries, officially started in November 2020.

In addition, the LIH Competence Centre for Methodology and Statistics (CCMS), led by Dr Michel Vaillant, together with the Digital Epidemiology and E-health unit, led by Dr Guy Fagherazzi, will contribute with the Predi-COVID study data to “unCoVer” (Unravelling Data for Rapid Evidence-Based Response to COVID-19), a functional network of research institutions collecting data derived from the care provided to COVID-19 patients by European and international healthcare services. These real-world data will enable the study of patient characteristics, risk factors, safety and effectiveness of treatments and potential strategies against COVID-19 in real clinical settings. The 24-month project, which counts 29 partners from 18 nations, officially started in November 2020.

Finally, the LIH Transversal Translational Medicine team, led by Prof Rejko Krüger, and CCMS will contribute to “ORCHESTRA” (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic). This 36-month project − which integrates ongoing efforts of the CON-VINCE study and of the National Centre of Excellence in Research on Parkinson’s disease (NCER-PD) − aims to provide an innovative approach to learning from the COVID-19 health crisis and deriving recommendations for increasing preparedness for future outbreaks. The main outcome of the project is the creation of a new pan-European cohort built on existing and new large-scale population and susceptible people cohorts in European and non-European countries. ORCHESTRA, which started in December 2020, involves 26 partners from 15 countries.

TRANSLATIONAL RESEARCH EXCELLENCE

Taking LIH findings “from the bench to the bed”

LIH aims to perform research that transcends the classical boundaries of individual diseases and that can be tangibly applied in the clinical practice to improve health outcomes for patients and society as a whole. In the context of this translational and transversal research strategy, LIH researchers published their high-impact findings in a variety of prestigious international journals throughout 2020, spanning the institute’s key priority areas. These publications will contribute to advancing the understanding and treatment of cancer, autoimmune diseases and neurodegenerative disorders, as well as offering new perspectives on public health and preventive medicine, thereby being concrete instances of translational “bed-to-bench-to-bed” research.

Fighting Autoimmunity and Cancer: The Nutritional Key

Prof Dirk Brenner, Head of the Experimental & Molecular Immunology research group of the Department of Infection and Immunity (DII), and postdoctoral fellow Henry Kurniawan revealed a novel mechanism through which the immune system can control autoimmunity and cancer.

Renewed hope for treatment of pain and depression

Dr Andy Chevigné, Dr Martyna Szpakowska and Max Meyrath from the Immuno-Pharmacology and Interactomics research group of the LIH Department of Infection and Immunity developed a novel molecule that binds to and blocks a previously unknown opioid receptor in the brain, thereby modulating the levels of opioid peptides produced in the central nervous system (CNS) and potentiating their natural painkilling and antidepressant properties.

Innovative machine- learning approach for future diagnostic advances in Parkinson’s disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease, although the detailed molecular and cellular mechanisms underlying its pathogenesis remains unclear. Recent evidence has pointed towards the role of mitochondrial dysfunction in the onset of the disease. Mitochondria — small cellular ‘subunits’ involved in cell metabolism and energy generation — constantly and dynamically interact with each other, forming perpetually changing networks known as mitochondria interaction networks (MINs). Since conventional research focusing on individual mitochondria has not provided satisfying insights into PD pathogenesis, Dr Feng He, Group Leader of the Immune Systems Biology research group of the LIH Department of Infection and Immunity, Prof Rejko Krüger, Director of Transversal Translational Medicine at LIH, and their teams investigated the interaction networks between these organelles, in order to understand the correlation between the mitochondrial impairments observed in PD and any specific network topological changes in MINs, ultimately aiming to advance the early diagnosis and classification of PD patients.

Improving cancer immunotherapy by turning “cold” tumours “hot”

Immune checkpoint inhibitors (ICI), exemplified by anti-PD-1, are immunotherapeutic drugs that act by removing the “brakes” on the immune system and unleashing an immune attack on cancer cells. Though very promising for the treatment of many cancers, only relatively few cancer patients show significant therapeutic benefits when treated with ICI alone. One of the major causes of tumour unresponsiveness to ICI is the poor infiltration of cytotoxic immune cells into the tumour bed.

New insights into Glioblastoma invasiveness

One of the hallmarks of Glioblastoma (GBM), the most aggressive type of brain cancer, is its high invasive capacity, which leads to its expansion into the normal brain tissue and migration to more distant locations, giving rise to metastases. ‘Stray’ cancer cells can therefore escape surgical resection, radio- and chemotherapy, thereby accounting for the limited success of current treatment approaches and for the poor patient prognosis observed. Novel molecular targets that regulate invasion and that can be leveraged during drug development are therefore a priority in modern-day oncology.

Advancing personalised cancer treatment through tumour organoids and patient “avatars”

The success of clinical trials is significantly dependent on the quality of the results obtained during preclinical drug testing studies on experimental models of a patient’s tumour, prior to the clinical phase. The availability of accurate and comprehensive models in the preclinical setting that reflect the full range of genetic variations observed in brain cancers and that are able to reliably predict the sensitivity of specific types of tumours to new personalised treatments is therefore of utmost importance for translational oncology.

Parkinson’s disease and the gut microbiome

Parkinson’s disease (PD) is a complex disease, shaped by both genetic and environmental factors. While the role of the former in the pathogenesis of the disease has been widely accepted, the contribution of various environmental and lifestyle factors remains largely unclear. For instance, constipation is one of the earliest symptoms of the disease, with recent studies reporting an altered gut microbiome composition in PD patients compared to age-matched controls.

Cholesterol levels dropping in Western nations but rising in Asia

High blood cholesterol has typically been regarded as a feature of wealthy western countries. However, dietary and behavioural determinants of blood cholesterol, as well as the adoption of medications such as statins, have been evolving throughout the world in the last decades. These changes have significantly altered the levels of HDL and non-HDL cholesterol worldwide, possibly with diverging geographical patterns. However, no global study had previously reported or quantified the trends in HDL and non-HDL cholesterol levels over time.

Fruit and vegetable intake prevents risk of type 2 diabetes

Type 2 diabetes (T2D) has become a major public health crisis over the last decades, with its prevention being a key priority globally. Diet, and particularly high fruit and vegetable intake, has been suggested to play an important role in the prevention of this metabolic disorder. Nevertheless, the lack of reliable evidence on their association remains a challenge. Previous studies suggested vitamin C and carotenoids circulating in the bloodstream as reliable biomarkers of fruit and vegetable intake. Investigating the association between these biomarkers and type 2 diabetes could therefore provide a clearer picture of the link between fruit and vegetable intake and T2D.

ADDITIONAL 2020 HIGHLIGHTS

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