A properly functioning immune system must be able to recognize foreign invaders among the multitude of cells in the body. This ability is essential to both fight infection and prevent autoimmune diseases. We study how a specific type of immune cells, known as T cells, are educated to make this distinction during development.
The thymus generates and selects a highly variable yet specific T cell repertoire which discriminates between self and non-self antigens. Within the thymus, medullary thymic epithelial cells express a diverse set of antigens, representing essentially all tissues of the body. This phenomenon, termed promiscuous gene expression, imposes central T cell self-tolerance by enabling peripheral antigens to be continuously accessible to developing T cells.
Ultimately, understanding the physiological mechanisms that lead to self-tolerance will be crucial in understanding autoimmunity and autoimmune diseases. Despite extensive work on the molecular basis of promiscuous gene expression, many questions concerning both single cell and tissue level organisation of antigen expression are unanswered. For instance, is promiscuous gene expression organised in a spatially or temporally restricted manner or a combination of both? How do thymic epithelial cells maintain their integrity despite expressing peripheral proteins that may interfere with epithelial-specific pathways and roles?
My research group seeks to answer these questions by combining genomics and mathematical modeling. We investigate the spatial and temporal organisation of promiscuous gene expression in the thymus and how antigen distribution in the thymus affects epithelial-T cell interaction and migration. Analogously, on single cell level, we conduct research on the spatio-temporal organisation of promiscuous gene expression to understand cellular integrity mechanisms in thymic epithelial cells.
Meyer, Hannah V and Dawes, Timothy JW and Serrani, Marta and Bai, Wenjia and Tokarczuk, Pawel and Cai, Jiashen and de Marvao, Antonio and Rueckert, Daniel and Matthews, Paul M and Costantino, Maria L and Birney, Ewan and Cook, Stuart A and O'Regan, Declan P (2019) Genomic analysis reveals a functional role for myocardial trabeculae in adults. bioRxiv, pp. 553651.
Meyer, H. V. and Birney, E. (2018) PhenotypeSimulator: A comprehensive framework for simulating multi-trait, multi-locus genotype to phenotype relationships. Bioinformatics, 34(17) pp. 2951-2956.
Meyer, Hannah Verena and Casale, Francesco Paolo and Stegle, Oliver and Birney, Ewan (2018) LiMMBo: a simple, scalable approach for linear mixed models in high-dimensional genetic association studies. bioRxiv, pp. 255497.
Biffi, C. and de Marvao, A. and Attard, M. I. and Dawes, T. J. W. and Whiffin, N. and Bai, W. and Shi, W. and Francis, C. and Meyer, H. and Buchan, R. and Cook, S. A. and Rueckert, D. and O'Regan, D. P. (2018) Three-dimensional cardiovascular imaging-genetics: a mass univariate framework. Bioinformatics, 34(1) pp. 97-103.
Keil, M. and Sonner, J. K. and Lanz, T. V. and Oezen, I. and Bunse, T. and Bittner, S. and Meyer, H. V. and Meuth, S. G. and Wick, W. and Platten, M. (2016) General control non-derepressible 2 (GCN2) in T cells controls disease progression of autoimmune neuroinflammation. J Neuroimmunol, 297 pp. 117-26.
Rattay, K. and Meyer, H. V. and Herrmann, C. and Brors, B. and Kyewski, B. (2016) Evolutionary conserved gene co-expression drives generation of self-antigen diversity in medullary thymic epithelial cells. J Autoimmun, 67 pp. 65-75.
Beer, R. and Herbst, K. and Ignatiadis, N. and Kats, I. and Adlung, L. and Meyer, H. and Niopek, D. and Christiansen, T. and Georgi, F. and Kurzawa, N. and Meichsner, J. and Rabe, S. and Riedel, A. and Sachs, J. and Schessner, J. and Schmidt, F. and Walch, P. and Niopek, K. and Heinemann, T. and Eils, R. and Di Ventura, B. (2014) Creating functional engineered variants of the single-module non-ribosomal peptide synthetase IndC by T domain exchange. Mol Biosyst, 10(7) pp. 1709-18.
Renner, M. and Wolf, T. and Meyer, H. and Hartmann, W. and Penzel, R. and Ulrich, A. and Lehner, B. and Hovestadt, V. and Czwan, E. and Egerer, G. and Schmitt, T. and Alldinger, I. and Renker, E. K. and Ehemann, V. and Eils, R. and Wardelmann, E. and Buttner, R. and Lichter, P. and Brors, B. and Schirmacher, P. and Mechtersheimer, G. (2013) Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas. Genome Biol, 14(12) pp. r137.Additional materials of the author at
CSHL Institutional Repository