Autoimmune and inflammatory diseases – novel treatment strategies
Inflammation is the host response following exposure to pathogens. This involves activation of the immune system that is built up by multiple, often overlapping, layers represented by cells, physical barriers and soluble factors working together to stop the invading pathogen.
Non-infectious conditions can also trigger inflammation, sometimes referred to as sterile inflammation to highlight the absence of pathogens. This is fiercely seen in patients with autoimmune diseases, where self-tissues become the target for the immune activation, e.g. the joints of patients with rheumatoid arthritis (RA). These diseases affect as much as 5% of the population and can lead to lifelong morbidity as well as to directly life-threatening situations.
Progress has been made regarding treatment alternatives for these patients. Still, novel treatments based on deeper understanding of the diseases is needed.
The general goal of our research is to use a translational approach to further understand inflammation, and thereby identify novel drug targets and biomarkers relevant for autoimmune disease and cancer immunotherapy.
Work plan and methods
A major focus is related to antibodies that are important effector molecules of our immune system. Besides antibodies, we have an interest in B cells and various myeloid cells, especially neutrophils and macrophages. We also spend a lot of effort into using CRISPR/Cas9 based custom screens as a discovery platform to understand complex biological processes and to identify novel drug targets.
Currently several projects in the lab relates to our interest in signaling downstream of the IL-4 receptor (IL-4R). The basis for this interest was the unexpected finding that the expression of the IL-4R on myeloid cells is essential for the activity of a drug (IVIG) used to treat patients with autoimmune disease, and that this receptor is highly regulated during inflammation (Anthony et al, 2011, Nature and Wermeling et al, 2013, PNAS).
- Studies of antibodies in patients with Rheumatic disease.
- Novel drug targets in patients with Rheumatic diseases; a role for IL-4R signaling.
- Therapeutic antibody treatment for Cancer; a role for myeloid-derived suppressor cells and IL-4R signaling.
- Custom CRISPR/Cas9 screens to identify drug targets in inflammatory diseases and Cancer.
Fredrik Wermeling, PhD, Assistant Professor, PI
Sudeepta Kumar Panda, PhD, Postdoc
Sanjay Boddul, PhD, Postdoc
Sergio Haller, PhD, Postdoc
Zsolt Kasza, PhD, Lab manager
- Wenner-Gren Foundations / Wenner-Gren Fellow program
- Swedish Foundation for Strategic Research / Ingvar Carlsson Award 2013
- The Swedish Research Council / Project Grant Junior Researchers
- Karolinska Institutet / Faculty Funded Career Position
- Swedish Cancer Society
- King Gustaf V 80-Year Foundation
- Jeansson Foundations
- The Alfhild Aquilin and Karl Bensen Memorial Foundation, and the Gösta and Karin Wahmans Memorial Foundation
- Alex and Eva Wallström Foundation for scientific research and education
- Åke Wiberg Foundation
- Börje Dahlin Foundation
Five selected publications
Acute inflammation primes myeloid effector cells for anti-inflammatory STAT6 signaling.
Proc. Natl. Acad. Sci. U.S.A. 2013 Aug;110(33):13487-91
Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway.
Nature 2011 Jun;475(7354):110-3
Invariant NKT cells limit activation of autoreactive CD1d-positive B cells.
J. Exp. Med. 2010 May;207(5):943-52
Identification of a receptor required for the anti-inflammatory activity of IVIG.
Proc. Natl. Acad. Sci. U.S.A. 2008 Dec;105(50):19571-8
Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus.
J. Exp. Med. 2007 Oct;204(10):2259-65
All publications by Fredrik Wermeling found at PubMed