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Eva Särndahl

Title: Professor School/office: School of Medical Sciences

Email:

Phone: +46 19 303684

Room: C2203

Eva Särndahl

About Eva Särndahl

Research

The Role of Inflammasome Signaling in Health and Disease

Eva Särndahl is professor in Medical microbiology at Örebro University in Sweden. She has more than 25 years of experience in signal transduction involved in the regulation of the inflammatory process both in keeping immunological homeostasis but also during the development of inflammatory-mediated diseases. During the last seven years, the focus has been set on the involvement of inflammasome signaling in health and disease. Especially the role of dysregulated signaling due to variations in genes encoding the NLRP3 inflammasome in order to understand the inter-individual differences that determine why some individuals respond with severe, life-threatening inflammation, whereas others display a quiescent progression, or even remain asymptomatic following microbial challenge. Currently, this is investigated in patients with sepsis induced by S. aureus, E. coli and N. meningitides as well as in the development of type 2-diabetes and cardiovascular disease.

Besides its role in sensing microbes and their pathogen-associated molecular patterns (PAMPs), the NLRP3 inflammasome detects danger-associated molecular patterns (DAMPs), like nano particles, asbestos and silica but also endogenous substances. In collaboration, the underlying mechanisms in host innate response to stimuli and stressors are investigated in order to understand inflammatory-mediated diseases, including cystic fibrosis, auto-inflammatory/autoimmune diseases, inflammation developed in foundry workers and surgery-induced inflammation.

Short Career Narrative

I defended my thesis at Linköping University in 1994. My thesis revealed that chemotactic receptors are turned off by a lateral segregation between the receptor and its transducing partner, i.e. the G-protein; data that also suggests the cytoskeleton to function as a scaffold for signal transduction. Two years later I started my own research group studying the involvement of pro vs. anti-inflammatory signaling on leukocyte adhesion in order to understand the progression of inflammation and its resolution. During this time, I was the recipient of the Swedish Cancer Society 2-year postdoc position in 1995, and a 4-year Assisting Professorship by the Swedish Medical Research Council in 1998. In 2000-01, I was a Fulbright Scholar in Dr. Charles Serhan´s laboratory at Harvard Medical School, USA studying and acquiring knowledge on the anti-inflammatory eicosanoid lipoxin. This work was awarded the national Crafoord research grant from the Royal Swedish Academy of Sciences.

In 2005, I was asked to join a project in which a rheumatologists and a geneticist needed help to understand the inflammatory mechanisms of a patient with auto-inflammatory symptoms. Polymorphisms of the NLRP3 inflammasome in combination with C10X in CARD8 were found to create an over-activated inflammasome resulting in elevated IL-1β production; thereby giving the patient his symptoms (Verma et al. 2008). The interest for inflammasome signaling was thereby uncovered, and has since been the main focus of my research. In 2007, got a professorship at Örebro University, and our research has been recognized by national founding as well as strategically research grants and positions from Örebro University. In 2013, the collaborative network “iRiSC - Inflammatory Response and Infection Susceptibility Centre” involving national and international researchers was launched with me as its Director. Read more about iRiSC.

 

Research Projects

Research Teams

Publications

Publications

Articles in journals |  Manuscripts | 

Articles in journals

Hylén, U. , Eklund, D. , Humble, M. B. , Bartoszek, J. , Särndahl, E. & Bejerot, S. (2020). Increased inflammasome activity in markedly ill psychiatric patients: An explorative study. Journal of Neuroimmunology, 339.
Hedbrant, A. , Andersson, L. , Bryngelsson, I. , Eklund, D. , Westberg, H. , Särndahl, E. & Persson, A. (2020). Quartz Dust Exposure Affects NLRP3 Inflammasome Activation and Plasma Levels of IL-18 and IL-1Ra in Iron Foundry Workers. Mediators of Inflammation.
Rasmussen, G. , Asfaw Idosa, B. , Monecke, S. , Bäckman, A. , Strålin, K. , Särndahl, E. & Söderquist, B. (2019). Caspase-1 Inflammasome Activity in Patients with Staphylococcus aureus Bacteremia. Microbiology and immunology, 63 (12), 487-499.
Westberg, H. , Hedbrant, A. , Persson, A. , Bryngelsson, I. , Johansson, A. , Ericsson, A. , Sjögren, B. , Stockfelt, L. & et al. (2019). Inflammatory and coagulatory markers and exposure to different size fractions of particle mass, number and surface area air concentrations in Swedish iron foundries, in particular respirable quartz. International Archives of Occupational and Environmental Health, 92 (8), 1087-1098.
Asfaw Idosa, B. , Kelly, A. , Jacobsson, S. , Demirel, I. , Fredlund, H. , Särndahl, E. & Persson, A. (2019). Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent. Journal of Immunology Research.
Andersson, L. , Bryngelsson, I. , Hedbrant, A. , Persson, A. , Johansson, A. , Ericsson, A. , Lindell, I. , Stockfelt, L. & et al. (2019). Respiratory health and inflammatory markers: Exposure to respirable dust and quartz and chemical binders in Swedish iron foundries. PLoS ONE, 14 (11).
Månsson, E. , Sahdo, B. , Nilsdotter-Augustinsson, Å. , Särndahl, E. & Söderquist, B. (2018). Lower activation of caspase-1 by Staphylococcus epidermidis isolated from prosthetic joint infections compared to commensals. Journal of bone and joint infection, 3 (1), 10-14.
Månsson, E. , Söderquist, B. , Nilsdotter-Augustinsson, Å. , Särndahl, E. & Demirel, I. (2018). Staphylococcus epidermidis from prosthetic joint infections induces lower IL-1 release from human neutrophils than isolates from normal flora. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 126 (8), 678-684.
Baban, B. , Ljungqvist, O. & Särndahl, E. (2016). Inflammasome activation, colonic cancer and glucose metabolism. Clinical Nutrition ESPEN, 12.
Hussain, S. , Varelogianni, G. , Särndahl, E. & Roomans, G. M. (2015). N-acetylcysteine and azithromycin affect the innate immune response in cystic fibrosis bronchial epithelial cells in vitro. Experimental Lung Research, 41 (5), 251-260.
Asfaw Idosa, B. , Sahdo, B. , Balcha, E. , Kelly, A. , Söderquist, B. & Särndahl, E. (2014). C10X polymorphism in the CARD8 gene is associated with bacteraemia. Immunity, inflammation and disease, 2 (1), 13-20.
Eklund, D. , Welin, A. , Andersson, H. , Verma, D. , Söderkvist, P. , Stendahl, O. , Särndahl, E. & Lerm, M. (2014). Human Gene Variants Linked to Enhanced NLRP3 Activity Limit Intramacrophage Growth of Mycobacterium tuberculosis. Journal of Infectious Diseases, 209 (5), 749-753.
Paramel, G. , Folkersen, L. , Strawbridge, R. J. , Elmabsout, A. , Särndahl, E. , Lundman, P. , Jansson, J. , Hansson, G. K. & et al. (2013). CARD8 gene encoding a protein of innate immunity is expressed in human atherosclerosis and associated with markers of inflammation. Clinical Science, 125 (8), 401-407.
Sahdo, B. , Fransén, K. , Asfaw Idosa, B. , Eriksson, P. , Söderquist, B. , Kelly, A. & Särndahl, E. (2013). Cytokine profile in a cohort of healthy blood donors carrying polymorphisms in genes encoding the NLRP3 inflammasome. PLoS ONE, 8 (10).
Sahdo, B. , Särndahl, E. , Elgh, F. & Söderquist, B. (2013). Propionibacterium acnes activates caspase-1 in human neutrophils. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 121 (7), 652-63.
Blomgran, R. , Patcha Brodin, V. , Verma, D. , Bergström, I. , Söderkvist, P. , Sjöwall, C. , Eriksson, P. , Lerm, M. & et al. (2012). Common genetic variations in the NALP3 inflammasome are associated with delayed apoptosis of human neutrophils. PLoS ONE, 7 (3).
Lönn, J. , Starkhammar Johansson, C. , Kälvegren, H. , Brudin, L. , Skoglund, C. , Garvin, P. , Särndahl, E. , Ravald, N. & et al. (2012). Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition. Results in Immunology, 2, 7-12.
Verma, D. , Särndahl, E. , Andersson, H. , Eriksson, P. , Fredrikson, M. , Jönsson, J. , Lerm, M. & Söderkvist, P. (2012). The Q705K polymorphism in NLRP3 is a gain-of-function alteration leading to excessive interleukin-1β and IL-18 production. PLoS ONE, 7 (4).
Börgeson, E. , Lönn, J. , Bergström, I. , Brodin, V. P. , Ramström, S. , Nayeri, F. , Särndahl, E. & Bengtsson, T. (2011). Lipoxin A(4) inhibits porphyromonas gingivalis-induced aggregation and reactive oxygen species production by modulating neutrophil-platelet interaction and CD11b expression. Infection and Immunity, 79 (4), 1489-1497.
Särndahl, E. , Bergström, I. , Nijm, J. , Forslund, T. , Perretti, M. & Jonasson, L. (2010). Enhanced neutrophil expression of annexin-1 in coronary artery disease. Metabolism: Clinical and Experimental, 59 (3), 433-440.
Fröbert, O. , Christensen, K. , Fahlman, Å. , Brunberg, S. , Josefsson, J. , Särndahl, E. , Swenson, J. E. & Arnemo, J. M. (2010). Platelet function in brown bear (Ursus arctos) compared to man. Thrombosis journal, 8, 11.
Verma, D. , Eriksson, P. , Sahdo, B. , Persson, A. , Ejdeback, M. , Särndahl, E. & Söderkvist, P. (2010). Two adult siblings with atypical Cryopyrin-associated periodic syndrome due to a novel M299V mutation in NLRP3. Arthritis and Rheumatism, 62 (7), 2138-2143.
Winberg, M. E. , Holm, A. , Särndahl, E. , Vinet, A. F. , Descoteaux, A. , Magnusson, K. , Rasmusson, B. & Lerm, M. (2009). Leishmania donovani lipophosphoglycan inhibits phagosomal maturation via action on membrane rafts.. Microbes and infection, 11 (2), 215-22.
Verma, D. , Lerm, M. , Blomgran Julinder, R. , Eriksson, P. , Söderkvist, P. & Särndahl, E. (2008). Gene polymorphisms in the NALP3 inflammasome are associated with interleukin-1 production and severe inflammation: relation to common inflammatory diseases?. Arthritis and Rheumatism, 58 (3), 888-894.
Welin, A. , Winberg, M. E. , Abdalla, H. , Särndahl, E. , Rasmusson, B. , Stendahl, O. & Lerm, M. (2008). Incorporation of Mycobacterium tuberculosis lipoarabinomannan into macrophage membrane rafts is a prerequisite for the phagosomal maturation block. Infection and Immunity, 76 (7), 2882-7.
Särndahl, E. , Bergström, I. , Brodin, V. P. , Nijm, J. , Lundqvist Setterud, H. & Jonasson, L. (2007). Neutrophil activation status in stable coronary artery disease. PloS one, 2 (10), e1056.

Manuscripts

Idosa, B. A. , Sahdo, B. , Balcha, E. , Kelly, A. , Söderquist, B. & Särndahl, E. C10X polymorphism in the CARD8 gene is associated with bacteraemia.
Rasmussen, G. , Asfaw Idosa, B. , Bäckman, A. , Monecke, S. , Strålin, K. , Särndahl, E. & Söderquist, B. Caspase-1 Inflammasome Activity in Patients with Staphylococcus aureus Bacteraemia.
Sahdo, B. , Fransén, K. , Idosa, B. A. , Eriksson, P. , Söderquist, B. , Kelly, A. & Särndahl, E. Cytokine profile in a cohort of healthy blood donors carrying polymorphisms in genes encoding the nlrp3 inflammasome.
Asfaw Idosa, B. , Jacobsson, S. , Kelly, A. , Fredlund, H. , Persson, A. & Särndahl, E. Human gene variants that regulate the NLRP3 activity limit the production of Neisseria meningitidis-induced IL-1β and IL-18.
Asfaw Idosa, B. , Persson, A. , Jacobsson, S. , Demirel, I. , Fredlund, H. , Särndahl, E. & Kelly, A. LOS-dependent Neisseria meningitidis-induced caspase-1 activation in human neutrophils.