Projekte

We are currently working on the following areas:

The inter-individual variation of the human immune system is caused by the interaction between genetics and environmental factors.

Genetic regulation of molecular and immune phenotypes

We study how genetic variation affects molecular and immune phenotypes such as gene expression, metabolites and cytokine responses to stimulations in health and patient cohort (T1D, HIV and Lyme etc). We develop computational methods and algorithms for fully exploit high-throughput datasets from the most recent profiling technologies, e.g., causal inference and deconvolution of the overall genetic regulation effects of gene expression into relevant cell types.

Publications

Integration of multi-omics & Single cell genomics

We integrate large multi-omics data sets and immune profiling of patient/control cohorts to unravel the genotype-phenotype map on a genome-wide scale and built computational models for predicting immune functions and disease risk. We also apply cutting-edge techniques to study genetic regulation of gene expression in response to stimuli at single-cell resolution and we develop novel computational approaches for single-cell biology. Recently, we combined two scRNA-seq technologies and sc-proteomics in whole blood and PBMC to determine changes in immune cell composition and activation in two independent dual-center patient cohorts, each with mild and severe COVID-19 cases. This study provides insights into systemic immune responses to SARS- CoV-2 and reveals profound alterations in the myeloid compartment associated with severe COVID-19. 

Publications

Genetic regulation of molecular and immune phenotypes 

Li Y, Oosting M, Smeekens SP, Jaeger M, Aguirre-Gamboa R, Le KTT, Deelen P, Ricano-Ponce I, Schoffelen T, Jansen AFM, Swertz MA, Withoff S, van de Vosse E, van Deuren M, van de Veerdonk F, Zhernakova A, van der Meer JWM, Xavier RJ, Franke L, Joosten LAB, Wijmenga C, Kumar V, Netea MG (2016) A Functional Genomics Approach to Understand Variation in Cytokine Production in Humans. Cell 167(4): 1099-1110 e1014.

Aguirre-Gamboa R, de Klein N, di Tommaso J, Claringbould A, van der Wijst MG, de Vries D, Brugge H, Oelen R, Vosa U, Zorro MM, Chu X, Bakker OB, Borek Z, Ricano-Ponce I, Deelen P, Xu CJ, Swertz M, Jonkers I, Withoff S, Joosten I, Sanna S, Kumar V, Koenen H, Joosten LAB, Netea MG, Wijmenga C, Consortium B, Franke L, Li Y (2020) Deconvolution of bulk blood eQTL effects into immune cell subpopulations. BMC Bioinformatics 21(1): 243.

Integration of multi-omics & Single cell genomics

 

Schulte-Schrepping J, Reusch N, Paclik D, Baßler K, Schlickeiser S, Zhang B, Krämer B, Krammer T, Brumhard S, Bonaguro L, Domenico ED, Wendisch D, Grasshoff M, Kapellos TS, Beckstette M, Pecht T, Saglam A, Dietrich O, Mei HE, Schulz AR, Conrad C, Kunkel D, Vafadarnejad E, Xu CJ, Horne A, Herbert M, Drews A, Thibeault C, Pfeiffer M, Hippenstiel S, Hocke A, Müller-Redetzky H, Heim KM, Machleidt F, Uhrig A, Jarcy LB de, Jürgens L, Stegemann M, Glösenkamp CR, Volk HD, Goffinet C, Raabe J, Kaiser KM, Vinh MT, Rieke G, Meisel C, Ulas T, Becker M, Geffers R, Witzenrath M, Drosten C, Suttorp N, Kalle C von, Kurth F, Händler K, Schultze JL, Aschenbrenner AC, Li Y, Nattermann J, Sawitzki B, Saliba AE, Sander LE, DC19O Initiative (DeCOI) (2020) Suppressive myeloid cells are a hallmark of severe COVID-19. medRxiv  2020.06.03.20119818;  doi: doi.org/10.1101/2020.06.03.20119818.

Bakker OB, Aguirre-Gamboa R, Sanna S, Oosting M, Smeekens SP, Jaeger M, Zorro M, Vosa U, Withoff S, Netea-Maier RT, Koenen H, Joosten I, Xavier RJ, Franke L, Joosten LAB, Kumar V, Wijmenga C, Netea MG, Li Y (2018) Integration of multi-omics data and deep phenotyping enables prediction of cytokine responses. Nat Immunol 19(7): 776-786.

Li Y, Oosting M, Deelen P, Ricano-Ponce I, Smeekens S, Jaeger M, Matzaraki V, Swertz MA, Xavier RJ, Franke L, Wijmenga C, Joosten LA, Kumar V, Netea MG (2016) Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi. Nat Med 22(8): 952-960.