Adaptive Immunity; Antifungal Agents; Chromatin; Chromatin Assembly and Disassembly; Drug Discovery; Drug Resistance, Multiple, Fungal; Gene Regulatory Networks; Histone Acetyltransferases; Histone Chaperones; Histone Deacetylase 1; Host-Pathogen Interactions; Inflammation Mediators; Innate Immunity; Multidrug Resistance-Associated Proteins
We study fundamental problems in infection and inflammation using a combination of molecular as well as genome-wide and systems biology approaches. We are particularly interested in a better understanding of the dynamic gene regulation during host-pathogen interplay, with a focus on human fungal pathogens such as Candida spp. On the apthogen side, we use reverse genetics (genome-scale gene deletions, RNA-Seq / Chip-Seq) to (i) identify virulence and antifungal drug resistance genes, and to (ii) decipher the role of histone modifications and chromatin in morphogenesis or cell fate determination. On the host side, we exploit transcriptomics of primary phagocytes (macrophages, dendritic cells, neutrophils) and T cells to study (i) the mechanisms of gene regulation underlying antifungal immunity, (ii) the interplay of adaptive (T cells) and innate (dendritic cells) immunity in fungal immune surveillance, (iii) type I interferon signaling to decipher how inflammation controls the function and activity of phagocytes, and (iv) the critical role of Th17 inflammation on pathogen elimination in invasive fungal diseases. Finally, we are interested to better understand the molecular basis and mechanisms of multidrug resistance mediated by eukaryotic ATP-binding cassette transporters which are implicated in anti-cancer and anti-infective drug resistance phenomena.
- Zwolanek, F., M. Riedelberger, V. Stolz, W. Ellmeier & K. Kuchler (2015). The non-receptor tyrosine kinase TEC controls fungal virulence by activating the caspase-8 inflammasome. PLoS Pathogens. 10:e1004525. doi: 10.1371/journal.ppat.1004525
- Wirnsberger* G., F. Zwolanek*, Asaoka T, Kozieradzki I, Tortola L, RA Wimmer, F Fresser, G Baier, WY Langdon, A Kavirayani, F Ikeda, K. Kuchler* & JM. Penninger* (2016). The E3-ubiquitin-ligase Cbl-b controls antifungal immune responses. Nature Medicine 22:915-23. doi: 10.1038/nm.4134. Epub 2016 Jul 18 (*Equal first & equal corresponding authors)
- Khunweeraphong N, Stockner T & K. Kuchler (2017). The structure of the human ABC transporter ABCG2 reveals a novel mechanism for drug extrusion. Sci Rep. 7(1):13767. doi: 10.1038/s41598-017-11794-w. PMID: 29061978
- Jenull S, Tscherner M, Gulati M, Nobile CJ, Chauhan N, Kuchler K (2017). The Candida albicans HIR histone chaperone regulates the yeast-to-hyphae transition by controlling the sensitivity to morphogenesis signals. Sci Rep. 7(1):8308. doi: 10.1038/s41598-017-08239-9.
- Majer, O., Bourgeois, C., F. Zwolanek, M. Mack, C. Lassing, D. Kerjaschki, M. Müller & K. Kuchler (2012). Type I interferon signaling promotes fatal immunopathology through the recruitment of inflammatory monocytes and neutrophils. PLoS Pathogens 8: e1002811