Prof. Dr. Manuela Rossol is the new FGW Professor of Molecular Immunology at the Brandenburg University of Technology Cottbus-Senftenberg (BTU) as of 01.10.2022.
The immune system undergoes age-related changes that are relevant for the aging process itself, as well as for the development of age-related inflammations, susceptibility to infections, cancers, and neurodegenerative processes. So-called autoimmunity is also of central importance for many diseases that are particularly common in old age; the connections are currently still poorly understood.
The new professorship will investigate immunologically relevant processes in age-associated diseases at the molecular level and develop new therapeutic approaches from the research.
Calcium and calciprotein particle-mediated differentiation of monocytes to calcium macrophages
Calcium and calciprotein particles (CPPs) can initiate the differentiation of monocytes into calcium macrophages without the addition of other growth factors. We are investigating the mechanisms leading to this differentiation and the role calcium macrophages play in various diseases.
Calcium and calciprotein particle-mediated activation of the Nlrp3 inflammasome
We are investigating the mechanisms and pro-inflammatory consequences of monocyte activation by calcium and calciprotein particles (CPPs) in rheumatic diseases, obesity and cardiovascular diseases. The aim is to better understand the activation of the Nlrp3 inflammasome in this context and to identify important switches to therapeutically influence this process.
Schematic summary of how calcium, calciprotein particles, and LPS activate the Nlrp3 inflammasome (from Jäger & Murthy et al. Nature Communications 2020).
Immunometabolic studies in monocytes
Monocytes respond to bacterial stimuli by reprogramming their metabolism. Disease-associated, but also due to environmental pollutants, this reprogramming can be altered and influence the functions of monocytes. The aim is to identify and understand such alterations in order to be able to intervene therapeutically or, in the case of environmental pollutants, to avoid exposure.
Monocytes are not a homogeneous cell population, but one can identify several subpopulations in the blood. Besides the classical monocytes, there are the intermediate and the non-classical monocytes, and within the classical monocytes one can also find the CD56+ monocyte subpopulation. These subpopulations are strongly influenced by disease, aging, and environmental factors. The goal is to identify such changes in the subpopulations and to elucidate the functional consequences of these changes.
Danger signal extracellular calcium initiates differentiation of monocytes into SPP1/osteopontin-producing macrophages. Murthy S, Karkossa I, Schmidt C, Hoffmann A, Hagemann T, Rothe K, Seifert O, Anderegg U, von Bergen M, Schubert K, Rossol M.Cell Death Dis. 2022 Jan 12;13(1):53. DOI: 10.1038/s41419-022-04507-3
Macrophages in obesity are characterised by increased IL-1β response to calcium-sensing receptor signals. Thrum S, Sommer M, Raulien N, Gericke M, Massier L, Kovacs P, Krasselt M, Landgraf K, Körner A, Dietrich A, Blüher M, Rossol M, Wagner U. Int J Obes (Lond) 2022 Oct;46(10):1883-1891. DOI: 10.1038/s41366-022-01135-x
Calcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis. Jäger E, Murthy S, Hahn M, Strobel S, Schmidt C, Peters A, Stäubert C, Sungur P, Venus T, Geisler M, Radusheva V, Raps S, Rothe K, Scholz R, Jung S, Pierer M, Seifert O, Chang W, Estrela-Lopis I, Raulien N, Krohn K, Sträter N, Hoeppener S, Schöneberg T, Rossol M, Ulf Wagner U (shared authorship). Nature Communications. 2020 Aug 25;11(1):4243. DOI: 10.1038/s41467-020-17749-6
Perturbation of the Monocyte Compartment in Human Obesity. Friedrich K, Sommer M, Strobel S, Thrum S, Blüher M, Wagner U, Rossol M. Front Immunol. 2019 Aug 8;10:1874 DOI: 10.3389/fimmu.2019.01874
Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes. Raulien N, Friedrich K, Strobel S, Rubner S, Baumann S, von Bergen M, Körner A, Krueger M, Rossol M, Wagner U (shared authorship). Front Immunol. 2017 May 29;8:609. DOI: 10.3389/fimmu.2017.00609
GPRC6A mediates Alum-induced Nlrp3 inflammasome activation but limits Th2 type antibody responses. Quandt D, Rothe K, Baerwald C, Rossol M. Sci Rep. 2015 Nov 25;5:16719. DOI: 10.1038/srep16719
Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors.Rossol M, Pierer M, Raulien N, Quandt D, Meusch U, Rothe K, Schubert K, Schöneberg T, Schaefer M, Krügel U, Bräuner-Osborne H, Baerwald C, Wagner U. Nature Communications. 2012;3:1329. DOI: 10.1038/ncomms2339
Link to Pubmed with all publications of M. Rossol: Pubmed