Leonid Padyukov

Description of the project

Background

Human complex diseases characterized by involvement of both environmental and genetic factors with important contribution from gene-gene and gene-environmental interaction. The pathways of most of diseases of this type are influenced through immunological mechanisms, e.g. inflammation.

Overall aim

We like to understand how genetic variations influence development and/or protection from human common complex inflammatory diseases.

Work plan and methods

To determine genetic component of the disease we perform analysis of genetic markers in several loci shown to be linked or associated with this disease, e.g. by genome wide SNP scan, dense mapping of the locus or using comparative genomics. Rheumatoid arthritis, myositis, SLE, IgA nephropathy, asthma, MCTD, Sjögren's syndrome, multiple sclerosis are subjects of our investigations during last years. We study cytokine and cytokine receptor genes, genes from HLA complex and other genes with functional links to immune responses. We pay special attention to identify the functionally important genetic markers, which may affect the structure of the molecule or may regulate important control functions.

For some of these markers we perform functional genetic studies using mRNA and protein expression analysis. Interference of common genetic variations with splicing mechanisms is one of our focuses in functional genetics. Such mechanisms are obvious background for gene-environment interaction. Copy number variations, haplotype analysis and population genetics are also in the area of our expertise, which gives us an ability to extend the role of established genetic factors to different ethnical groups and populations. In addition, we are working with pharmacogenomics of RA, specifically in relation to MTX and anti-TNF treatment.

Our research strategy is to combine a translational approach with basic science using analysis of clinical material and exploring new bioinformatics tools.

Expected impact of results

Understanding of disease mechanisms through study of genetics will improve efficacy of diagnostics and will point on new potential targets for disease treatment.

Collaborations

We are working in collaboration with several Swedish Universities, including Uppsala, Lund, Göteborg, Linköping and Umeå.

Our major international collaborators are in The Broad Institute, MIT, Boston, MA; The Feinstein Institute for Medical Research, Manhasset, NY; The Genome Institute of Singapore, Leiden Medical University Centre, The Netherlands; Hanoi State University, Vietnam and Institute for Medical Research, Kuala Lumpur, Malaysia and University of Ohio, Columbus, OH.

Financing

• The Swedish Research Council
• The Swedish Rheumatism Association
• AFA
• Autocure, EU grant, 6th Framework
• NIH, National institutes of Health

The research group

• Leonid Padyukov, group supervisor
• Maria Seddighzadeh, PhD, assistant Professor
• Emeli Lundström, PhD student
• Mai Vuong Tuyet, PhD student
• Marcus Ronninger, PhD student
• Sigrid Lundberg, PhD student
• Too Chun Lai, PhD student
• Saedis Saevarsdottir, post doc

Five selected publications

• Search PubMed for Padyukov L