T cell effector function, post-transcriptional gene regulation, RNA binding proteins

Our Focus
My lab studies how T cell responses against tumours and infections are generated and maintained. We 1) study T cell responses against Non-Small Cell Lung Cancer (NSCLC) and paediatric neuroblastoma, with the aim to bring TIL therapy to the clinic. T cell products are also generated for cancer patients from peripheral-blood T cells for the production of e.g. CAR or TCR-transgenic T cells. Therefore, we 2) investigate the heterogeneity and functionality of blood-derived human T cells, in particular how this heterogeneity translates into their capacity to kill target cells, and how most potent T cell products can be generated and maintained. Furthermore, it is critical to decipher the molecular mechanisms that drive T cell effector function. We therefore 3) investigate how post-transcriptional events define T cell function and how it can be modified, with a specific focus on the role of RNA-binding proteins herein. We recently set up analysis pipelines to define the role of sequence determinants in transcripts in the protein output from transcripts. Unravelling these regulatory mechanisms in protein expression are thus key to our understanding of T cell functionality.
About Monika Wolkers

Monika Wolkers
My Research
Monika Wolkers did her PhD research at the Netherlands Cancer Institute on antigen presentation in the group of Ton Schumacher. After her postdoctoral training on the molecular imprinting of T cell memory in the groups of Stephen Schoenberger, Douglas Green (La Jolla Institute, San Diego and St Jude’s Children’s Hospital, Memphis) and on the role of aptoptosis molecules in immune responses in Jan Paul Medema’s lab (Amsterdam UMC), she started her research group in 2010 at Sanquin. Her research focusses on T cell effector function in health and disease.
Key Publications
Nicolet BP, Guislain A, van Alphen F, van den Biggelaar M, Gomez-Eerland R, Schumacher TN, Wolkers MC. CD29 identifies IFN-g producing human CD8+ T cells with an increased cytotoxic potential. Proceedings of the National Academy of Science. 2020. 117: 6686-6696
De Groot R*, van Loenen MM*, Guislain A, van den Heuvel MM, de Jong J, Burger P, Spaapen RM, Amsen D, Haanen JBAG, Monkhorst K, Hartemink KJ, Wolkers MC. Polyfunctional tumor-reactive T cells are effectively expanded from non-small cell lung cancers, and correlate with an immune-engaged T cell profile. Oncoimmunology 2019. 8(11):e1648170
Salerno F, Guislain A, Freen-van Heeren JJ, Nicolet B, Young HA, Wolkers MC. Critical role of post-transcriptional regulation for IFN-γ in tumor-infiltrating T cells. Oncoimmunology, 2018. 8:e1532762.
Salerno F, Engels S, van den Biggelaar M, van Alphen F, Guislain A, Zhao W, Hodge D, Bell SE, Medema JP, von Lindern M, Turner M, Young HA, and Wolkers MC. Translation repression through AU-rich elements prevents aberrant cytokine production in memory T cells. Nature Immunology, 2018. 19:828-837.
Salerno F, Pasolini NA, Stark R, von Lindern M, Wolkers MC. Distinct PKC-mediated post-transcriptional events set cytokine production kinetics in CD8+ T cells. Proceedings of the National Academy of Science, 2017. 114:9677-9682.
Members
Monika Wolkers Group leader | Anouk Jurgens OIO | Antonia Bradarić Research Technician |
Branka Popovic Post Doc | Kaspar Bresser PostDoc | Koos Rooijers Bioinformatician |
Leyma Wardak PhD student | Maria Valeria Lattanzio Onderzoek in opleiding | Maxime Steinmetz PhD Student |
Nandhini Kanagasabesan Junior Bioinformatician | Nestor Martin Analyst | Nila H. Servaas PostDoc |
Suzanne Castenmiller Technician | Zan Hozjan PhD student |