since 2020 Junior Group Leader/Molecular Immunology, University of Freiburg, Germany
2016 – 2020 Senior Research Fellow, National University of Singapore, Singapore
2013 – 2015 Research Fellow, National University of Singapore, Singapore
2010 – 2013 Research Associate, The Scripps Research Institute, La Jolla, USA
2006 – 2010 Ph.D. in Molecular Immunology, University of London, Imperial College, UK
2005 – 2006 M.Res. in Molecular and Cellular Basis of Infection. University of London, Imperial College London, UK
2002 – 2005 B.Sc. (Hons.) in Biology, University of London, Imperial College London, UK
Research interests:
- Immunoreceptor signaling: positive and negative regulation of lymphocyte signaling
- T cell-based immunotherapies against autoimmunity and cancer
Publications:
Research papers:
Gascoigne N, Wojciech L, Prasad M, Brzostek J, Rybakin V, Hoerter J, Hou B, Tung D, Chua YL, Ampudia J, Rai A, Chodaczek G, Fu G, Pettersson S (2025) The role of Themis in development of type 2 diabetes. Res Sq preprint
Tang J, Jia X, Zeng T, Bao Y, Hu Y, Dong J, Xu X, Chen XL, Liu Y, Wang J, Hou B, Zhu Y, Fu GF, Zheng Q, Chen Y, Li W, Ren T, Zhang L, Jiang S, Cong Y, Quan M, Yan C, Lin S, Wang N, Liu S, Huang C, Hou L, Teijaro J, Brzostek J, Gautam N, Xiao C, Wang Y, Li G, Xu B, Hui E, Wang HR, Gascoigne NRJ, Fu G (2025) Themis dominates T cell exhaustion by regulation of TCR and PD-1 signaling. bioRxiv preprint
Hamidinia M, Gu Y, Ser Z, Brzostek J, Tay NQ, Yap J, Chua YL, Limn YT, Wood KJ, Vathsala A, Sobota RM, MacAry PA, Gascoigne NRJ (2025) Occlusion of TCR binding to HLA‐A*11:01 by a non‐pathogenic human alloantibody. Cellular and Molecular Life Sciences 82:94
Gautam N, Wojciech L, Yap J, Chua YL, Ding EM, Sim DC, Tan AS, Ahl PJ, Prasad M, Tung DW, Connolly JE, Adriani G, Brzostek J, Gascoigne NR. (2023) Themis controls T cell activation, effector functions, and metabolism of peripheral CD8+ T cells. Life Science Alliance 6:e202302156.
Wu L, Brzostek J, Sakthi Vale PD, Wei Q, Koh CKT, Ong JXH, Wu LZ, Tan JC, Chua YL, Yap J, Song Y, Tan VJY, Tan TYY, Lai J, MacAry PA, Gascoigne NRJ. (2023) CD28-CAR-T cell activation through FYN kinase signaling rather than LCK enhances therapeutic performance. Cell Reports Medicine 4:100917.
Wu LZ, Balyan R, Brzostek J, Zhao X, Gascoigne NRJ. (2023) Time required for commitment to T cell proliferation depends on TCR affinity and cytokine response. EMBO Reports 24:e54969.
Liu Y, Cong Y, Niu Y, Yuan Y, Tan F, Lai Q, Hu Y, Hou B, Li J, Lin C, Zheng H, Dong J, Tang J, Chen Q, Brzostek J, Zhang X, Chen XL, Wang HR, Gascoigne NRJ, Xu B, Lin SH, Fu G. (2022) Themis is indispensable for IL-2 and IL-15 signaling in T cells. Science Signaling 15:eabi9983.
Zhao X, Wu LZ, Ng EKY, Leow KWS, Wei Q, Gascoigne NRJ, Brzostek J. (2021) Non-stimulatory pMHC enhance CD8 T cell effector functions by recruiting coreceptor-bound Lck. Frontiers in Immunology 12:721722.
Banik D, Hamidinia M, Brzostek J, Wu L, Stephens HM, MacAry PA, Reinherz EL, Gascoigne NRJ, Lang MJ. (2021) Single molecule force spectroscopy reveals distinctions in key biophysical parameters of αβ T-cell receptors compared with chimeric antigen receptors directed at the same ligand. The Journal of Physical Chemistry Letters 31:7566-7573.
Prasad M, Wojciech L, Brzostek J, Hu J, Chua YL, Tung DWH, Yap J, Rybakin V, Gascoigne NRJ. (2021) Expansion of an unusual virtual memory CD8+ subpopulation bearing Vα3.2 TCR in Themis-deficient mice. Frontiers in Immunology 12:644483.
Wu L, Brzostek J, Sankaran S, Wei Q, Yap J, Tan TYY, Lai J, MacAry PA, Gascoigne NRJ. (2021) Targeting CAR to the peptide-MHC complex reveals distinct signaling compared to that of TCR in a Jurkat T cell model. Cancers 13:867.
Prasad M, Brzostek J, Gautam N, Balyan R, Rybakin V, Gascoigne NRJ. (2021) Themis regulates metabolic signaling and effector functions in CD4+ T cells by controlling NFAT nuclear translocation. Cellular & Molecular Immunology 18:2249-2261.
Brzostek J, Gautam N, Zhao X, Chen EW, Mehta M, Tung DWH, Chua YL, Yap J, Cho SH, Sankaran S, Rybakin V, Fu G, Gascoigne NRJ. (2020) T cell receptor and cytokine signal integration in CD8+ T cells is mediated by the protein Themis. Nature Immunology 21:186-198.
Wei Q, Brzostek J, Sankaran S, Casas J, Hew L S-Q, Yap J, Zhao X, Wojciech L, Gascoigne NRJ. (2020) Lck bound to coreceptor is less active than free Lck. PNAS, 117:15809-15817.
Brzostek J*, Fatin A, Chua WH, Tan HY, Dick T, Gascoigne NRJ. (2020) Single cell analysis of drug susceptibility of Mycobacterium abscessus during macrophage infection. Antibiotics 9:711 *co-corresponding author
Chen EW, Tay NQ, Brzostek J, Gascoigne NRJ, Rybakin V. (2019) A dual inhibitor of Cdc7/Cdk9 potently suppresses T cell activation. Frontiers in Immunology 10:1718.
Zhao X, Hamidinia M, Choo JAL, Too CT, Ho ZZ, Ren EC, Bertoletti A, MacAry PA, Gould KG, Brzostek J*, Gascoigne NRJ. (2019) Use of single chain MHC technology to investigate co-agonism in human CD8+ T cell activation. Journal of Visualized Experiments, 144, doi: 10.3791/59126 *co-corresponding author
Chen EW, Ke CY, Brzostek J, Gascoigne NRJ, Rybakin V. (2019) Identification of mediators of T-cell receptor signaling via the screening of chemical inhibitor libraries. Journal of Visualized Experiments, 143 doi: 10.3791/58946.
Mehta M, Brzostek J, Chen EW, Tung DWH, Chen S, Sankaran S, Yap J, Rybakin V, Gascoigne NRJ. (2018) Themis-associated phosphatase activity controls signaling in T cell development. PNAS 115:E11331-E11340.
Zhao X, Sankaran S, Yap J, Too CT, Ho ZZ, Ren EC, Bertoletti A, MacAry AP, Brzostek J*, Gascoigne NRJ. (2018) Non-stimulatory peptide-MHC enhance human T cell responses to antigens by amplifying proximal TCR signalling strength. Nature Communications, 9:2716, 2018 *co-corresponding author
Chen EW, Brzostek J, Gascoigne NRJ, Rybakin V. (2018) Development of a screening strategy for new modulators of T cell receptor signaling and T cell activation. Scientific Reports 8:10046.
Almeida FF, Tenno M, Brzostek J, Li JL, Allies G, Hoeffel G, See P, Ng LG, Fehling HJ, Gascoigne NR, Taniuchi I, Ginhoux F. (2015) Identification of a novel lymphoid population in the murine epidermis. Scientific Reports 5:12554.
Casas J, Brzostek J, Zarnitsyna VI, Hong JS, Wei Q, Hoerter JA, Fu G, Ampudia J, Zamoyska R, Zhu C, Gascoigne NR. (2014) Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor. Nature Communications 5:5624.
Fu G, Casas J, Rigaud S, Rybakin V, Lambolez F, Brzostek J, Hoerter JA, Paster W, Acuto O, Cheroutre H, Sauer K, Gascoigne NR. (2013) Themis sets the signal threshold for positive and negative selection in T-cell development. Nature 504:441-5.
Hoerter JA, Brzostek J, Artyomov MN, Abel SM, Casas J, Rybakin V, Ampudia J, Lotz C, Connolly JM, Chakraborty AK, Gould KG, Gascoigne NR. (2013) Coreceptor affinity for MHC defines peptide specificity requirements for TCR interaction with coagonist peptide-MHC. Journal of Experimental Medicine 210:1807-21.
Kotsiou E, Brzostek J, Lenart I, Antoniou AN, Dyson J, Gould KG. (2011) Dimerization of soluble disulfide trap single-chain major histocompatibility complex class I molecules dependent on peptide binding affinity. Antioxidants and Redox Signaling 15:635-44.
Köhler K, Xiong S, Brzostek J, Mehrabi M, Eissmann P, Harrison A, Cordoba SP, Oddos S, Miloserdov V, Gould K, Burroughs NJ, van der Merwe PA, Davis DM. (2010) Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells. PLoS One 5:e15374.
Brzostek J, Chai JG, Gebhardt F, Busch DH, Zhao R, van der Merwe PA, Gould KG. (2010) Ligand dimensions are important in controlling NK-cell responses. European Journal of Immunology 40:2050-9.
Hitchen P, Brzostek J, Panico M, Butler JA, Morris HR, Dell A, Linton D. (2010) Modification of the Campylobacter jejuni flagellin glycan by the product of the Cj1295 homopolymeric-tract-containing gene. Microbiology 156:1953-62.
Williams GS, Collinson LM, Brzostek J, Eissmann P, Almeida CR, McCann FE, Burshtyn D, Davis DM. (2007) Membranous structures transfer cell surface proteins across NK cell immune synapses. Traffic 8:1190-204.
Reviews:
Huang L, Fu Y, Sun W, Brzostek J. (2021) Editorial: Vibrio virulence regulation and host interactions. Frontiers in Cellular and Infection Microbiology 11:793464.
Wu L, Wei Q, Brzostek J, Gascoigne NRJ. (2020) Signaling from T cell receptors (TCRs) and chimeric antigen receptors (CARs) on T cells. Cellular & Molecular Immunology 17:600–612.
Brzostek J, Gascoigne NRJ. (2017) Thymic origins of T cell receptor alloreactivity. Transplantation 101:1535-1541.
Gascoigne NRJ, Rybakin V, Acuto O, Brzostek J. (2016) TCR signal strength and T cell development. Annual Review of Cell and Developmental Biology 32:327-348.
Brzostek J, Gascoigne NR, Rybakin V. (2016) Cell type-specific regulation of immunological synapse dynamics by B7 ligand recognition. Frontiers in Immunology, 7:24.
Fu G, Rybakin V, Brzostek J, Paster W, Acuto O, Gascoigne NR. (2014) Fine-tuning T cell receptor signaling to control T cell development. Trends in Immunology, 35:311-8.
Gascoigne NR, Casas J, Brzostek J, Rybakin V. (2011) Initiation of TCR phosphorylation and signal transduction. Frontiers in Immunology, 2:72.
Kotsiou E, Brzostek J, Gould KG. (2011) Properties and applications of single-chain major histocompatibility complex class I molecules. Antioxidants and Redox Signaling, 15:645-55, 2011