The laboratory of the Inflammation & Biomarkers Group, led by the Ikerbasque Research Professor Koen Vandenbroeck, is a research group at Biocruces Bizkaia Health Research Institute and it is also affiliated to the Biochemistry and Molecular Biology department at Basque Country University (UPV/EHU). The main research lines of this group are the following:
Biomarkers and genomics in Multiple Sclerosis
This research line forms the main focus of the group. Over the years, our group has contributed to elucidating the genetics of Multiple Sclerosis (MS); we were among the first to report SOCS1, ANKRD55, IL7R as risk genes for MS, and we also analyzed pharmacogenomics of immunomodulatory treatments for MS. More recent work focused on the functional analysis of two MS risk genes, IL22RA2 and ANKRD55. Recently the focus of our research moved toward application of high depth RNAseq trancriptomics to the study of immune deviations seen in MS, a technique which allows mapping of mRNA splice variants and transcribed genomic variants. With this resource of information, a powerful bioinformatics analysis frame incorporating genomic variants and transcript counts for mapping inter individual variation can be devised to identify expression quantitative loci (eQTLs), loci regulating expression of genes in cis or trans. We are applying this approach to dendritic celll (DC) categories (pDC, cDC, and inflammatory DCs) in order to find potential biomarkers or novel targets for therapeutic intervention in MS in collaboration with neurologists at Cruces, Galdakao and Txagorritxu University Hospitals (Funded projects by ISCIII Health Research Project funding, EME society, RICORS and Basque Government Health Research Projects). DCs are cells at the interface of innate and acquired immunity and play crucial roles in autoimmune etiopathogenesis. There is extensive literature documenting a role for DC in many aspects related to MS disease progression and outcomes including drug response in MS. Specifically we are comparing the transcriptomes of two types of blood-circulating DC, plasmacytoid and conventional, to find out if transcriptomes of these cells could help us to differentiate the disease process in primary progressive (PP) patients from that in relapsing remitting (RR) course. Since few therapeutic options are currently available for PP MS, we hope that our work will make a difference in this regard, and lay the basis for new treatment options in PP MS.
Identification of risk variants for severe course of COVID-19 based on genomic variant microarray analysis
In view of the COVID-19 pandemia and the need to understand the genetic basis of severe clinical course independent of underlying comorbidities, we started a study to identify crucial genomic variants, in collaboration with clinical specialists at Galdakao U.H. and Cruces U.H., supported by the Health Department of the Basque Government (Basque Government Health Research Projects Call, 2020). Four types of severity of COVID-19 viral pneumonia have been observed ranging from mild over moderate (clinical signs of pneumonia, SpO2≥90%) to severe (SpO2<90%) and critical (acute respiratory stress syndrome) disease. We are using a specifically designed array for genetic studies in COVID-19 (i.e. Axiom Human Genotyping SARS-CoV-2 Research Array), which covers more than 800.000 variants, to gather information on genomic variants. Specifically we are studying the differences between patients with pneumonia COVID-19 vs patients with pneumonia non-COVID-19. As part of this work we are also trying to identify markers associated with severity of the disease. To this purpose, samples from hospitalized COVID-19 patients and individuals with positive PCR for SARS-CoV-2 but without symptoms are being collected. Hospitalized patients are stratified as severe or non-severe according to the OMS definitions (n>1500). We are executing genetic analysis using GWAS analysis tools from R program, including SNPassoc, qqman, etc.
Biomarkers of unstable carotid atherosclerotic plaque and stroke
We are developing strategies for the identification of genomic biomarkers with prognostic value for risk of suffering a cerebrovascular accident (CVA) in collaboration with vascular neurologists from IIS Biocruces Bizkaia. The research centers on carotid atherosclerotic plaques, which are builds-up of lipid deposits with associated inflammation in the cervical arteries. Specifically, vulnerability of the carotid plaque has been linked to enhanced risk for stroke. We identified by means of RNAseq analysis a group of genes that are differentially regulated in carotid atherosclerotic plaques surgically excised from symptomatic (patients having experienced stroke over the last 6 months, with carotid artery stenosis >70%) vs asymptomatic (no lifetime history of stroke, with carotid artery stenosis >80%) patients. are now validating these results in additional cohorts from national and international collaborators in order to lay the basis for the design of a marker panel that can be clinically implemented. This RNAseq study has also provided us with information on candidate SNPs with QTL effects associated with plaque instability, and some of these SNPs have been analysed and validated (Patented: EP19382103.0) while a more extended analyis is currently ongoing. All these data reveal a clear distinction between the pathways involved in the development of carotid plaques in symptomatic vs asymptomatic patients. Our purpose is to advance in technological development on the identification of biomarkers in order to implement these results in clinical practice.
Equipment of the group includes a BioRad QX200 Droplet Digital PCR Systems, ABI 7500Fast QPCR System and Miltenyi MACSQuant Analyzer 10 flow cytometer. Biocruces institute and UPV/EHU offer genetic-genomic platform services available to us (2100 Bionalyzer (Agilent Technologies), Iontorrent PGM (Life Technologies), SureScan Microarray Scanner (Agilent Technologies), digital PCR BIOMARK HD System (Fluidigm), MiSeq sequencer (Illumina), NovaSeq 6000 (Illumina)).
Life & Medical Sciences
- Biosciences & Health
- Biomarkers and genomics in Multiple Sclerosis
- Identification of risk variants for severe course of COVID-19 based on genomic variant microarray analysis
- Biomarkers of unstable carotid atherosclerotic plaque and stroke