RCI Regensburg Centre for Interventional Immunology
c/o University Hospital Regensburg
F.-J.-Strauss Allee 11 | D-93053 Regensburg
phone: +49 (0) 941 944-5480
Immune cells can recognize and kill tumor cells, but the complex tumor tissue often creates a suppressive environment that renders immune cells dysfunctional. Epigenetic mechanisms such as the packaging or modification of an immune cell’s DNA contribute to establish and maintain specific cellular states. These mechanisms are hence involved in “locking” cells in their unresponsive state, preventing treatments that aim at boosting immune cell’s function to fight tumor cells. We aim to understand and prevent the complex molecular processes that are involved in immune cell dysfunction to explore new treatment options.
We are interested how the non-coding part of our genome can interpret intrinsic and extrinsic cues to orchestrate differential gene expression in a tightly controlled spatiotemporal manner. After all, these astonishing mechanisms enable a single cell to develop to a complex organism with hundreds of specialized cell types, which all carry basically the same DNA sequence. Immune cells are an ideal system to study gene regulation, as many cell types are easily accessible from blood, and can be manipulated with tools that have been developed over decades.
In the past, we only were able to sequence populations of cells. Currently, the development of single-cell sequencing methods has broadly widened our understanding of cell-to-cell variability, cellular plasticity and heterogeneity of cell. We are interested in refining and applying single-cell methods to study heterogeneous and highly dynamic cell populations such as immune and cancer cells.
Interfering with co-inhibitory pathways can re-invigorate dysfunctional T cells and induce durable anti-tumor responses. However, tumor infiltrating lymphocytes (TILs) are a heterogeneous population of cells, and their true cellular state, stability and lineage relation remain to be elucidated to better predict treatment response, facilitate the development of new therapies, and to rationally design combinatory treatments. We want to use state-of-the art sequencing methods to understand underlying molecular causes of immune-cell (dys-)function in the tumor microenvironment with the aim to improve T cell targeting immunotherapies.
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- Schmidl C, Renner K, Peter K, Eder R, Lassmann T, Balwierz PJ, Itoh M, Nagao-Sato S, Kawaji H, Carninci P, et al: Transcription and enhancer profiling in human monocyte subsets. Blood 2014, 123:e90-99.
- Schmidl C, Hansmann L, Lassmann T, Balwierz PJ, Kawaji H, Itoh M, Kawai J, Nagao-Sato S, Suzuki H, Andreesen R, et al: The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations. Blood 2014, 123:e68-78.
- The FANTOM Consortium, Forrest AR, Kawaji H, Rehli M, Baillie JK, de Hoon MJ, Haberle V, Lassmann T, et al: A promoter-level mammalian expression atlas. Nature 2014, 507:462-470.
- Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao X, Schmidl C, Suzuki T, et al: An atlas of active enhancers across human cell types and tissues. Nature 2014, 507:455-461.
- Pham TH, Minderjahn J, Schmidl C, Hoffmeister H, Schmidhofer S, Chen W, Längst G, Benner C, Rehli M: Mechanisms of in vivo binding site selection of the hematopoietic master transcription factor PU.1. Nucleic Acids Res 2013, 41:6391-6402.
- Hansmann L, Schmidl C, Kett J, Steger L, Andreesen R, Hoffmann P, Rehli M, Edinger M: Dominant Th2 differentiation of human regulatory T cells upon loss of FOXP3 expression. J Immunol 2012, 188:1275-1282.
- Schmidl C*, Hansmann L*, Andreesen R, Edinger M, Hoffmann P, Rehli M: Epigenetic reprogramming of the RORC locus during in vitro expansion is a distinctive feature of human memory but not naive Treg. Eur J Immunol 2011, 41:1491-1498.
- Hansmann L*, Schmidl C*, Boeld TJ*, Andreesen R, Hoffmann P, Rehli M, Edinger M: Isolation of intact genomic DNA from FOXP3-sorted human regulatory T cells for epigenetic analyses. Eur J Immunol 2010, 40:1510-1512.
- Schmidl C, Klug M, Boeld TJ, Andreesen R, Hoffmann P, Edinger M, Rehli M: Lineage-specific DNA methylation in T cells correlates with histone methylation and enhancer activity. Genome Res 2009, 19:1165-1174.
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*) Equally contributing