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• Borowicz, Pawel; Gilmour, Brian Christopher; Chan, Hanna; Gopalakrishnan, Ramakrishna Prabhu; Peters, Timo & Platzer, René [Show all 20 contributors for this article] (2026). Intrinsically disordered insert from SH2D2A rewires CD19 CAR signaling via Tyr290 | bioRxiv. bioRxiv. ISSN 2692-8205. doi: 10.64898/2026.02.03.703491. Full text in Research Archive Show summary

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• Huszenicza, Zsuzsa; Gilmour, Brian Christopher; Koll, Lise; Kjelstrup, Hanna; Chan, Hanna & Sundvold, Vibeke [Show all 8 contributors for this article] (2024). Interaction of T-cell-specific adapter protein with Src- and Tec-family kinases. Scandinavian Journal of Immunology. ISSN 0300-9475. 99(5). doi: 10.1111/sji.13358. Full text in Research Archive Show summary

  Adapter proteins are flexible and dynamic modulators of cellular signalling that are important for immune cell function. One of these, the T-cell-specific adapter protein (TSAd), interacts with the non-receptor tyrosine kinases Src and Lck of the Src family kinases (SFKs) and Itk of the Tec family kinases (TFKs). Three tyrosine residues in the TSAd C-terminus are phosphorylated by Lck and serve as docking sites for the Src homology 2 (SH2) domains of Src and Lck. The TSAd proline-rich region (PRR) binds to the Src homology 3 (SH3) domains found in Lck, Src and Itk. Despite known interactors, the role TSAd plays in cellular signalling remains largely unknown. TSAd's ability to bind both SFKs and TFKs may point to its function as a general scaffold for both kinase families. Using GST-pulldown as well as peptide array experiments, we found that both the SH2 and SH3 domains of the SFKs Fyn and Hck, as well as the TFKs Tec and Txk, interact with TSAd. This contrasts with Itk, which interacts with TSAd only through its SH3 domain. Although our analysis showed that TSAd is both co-expressed and may interact with Fyn, we were unable to co-precipitate Fyn with TSAd from Jurkat cells, as detected by Western blotting and affinity purification mass spectrometry. This may suggest that TSAd-Fyn interaction in intact cells may be limited by other factors, such as the subcellular localization of the two molecules or the co-expression of competing binding partners.

• Gilmour, Brian Christopher; Corthay, Alexandre Benoit & Øynebråten, Inger (2024). High production of IL-12 by human dendritic cells stimulated with combinations of pattern-recognition receptor agonists. npj Vaccines. 9:83(1), p. 1–12. doi: 10.1038/s41541-024-00869-1. Full text in Research Archive Show summary

  The cytokine IL-12p70 is crucial for T helper 1 (Th1) polarization and the generation of type 1 immunity required to fight cancer and pathogens. Therefore, strategies to optimize the production of IL-12p70 by human dendritic cells (DCs) may significantly improve the efficacy of vaccines and immunotherapies. However, the rules governing the production of IL-12p70 remain obscure. Here, we stimulated pattern recognition receptors (PRRs) representing five families of PRRs, to evaluate their ability to elicit high production of IL-12p70 by monocyte-derived DCs. We used ten well-characterized agonists and stimulated DCs in vitro with either single agonists or 27 different combinations. We found that poly(I:C), which engages the RNA-sensing PRRs TLR3 and MDA5, and LPS which stimulates TLR4, were the only agonists that could elicit notable IL-12p70 production when used as single ligands. We identified six different combinations of PRR agonists, all containing either the TLR3/MDA5 agonist poly(I:C) or the TLR7/8 agonist R848, that could synergize to elicit high production of IL-12p70 by human DCs. Five of the six combinations also triggered high production of the antiviral and antitumor cytokine IFNβ. Overall, the tested PRR ligands could be divided into three groups depending on whether they triggered production of both IL-12p70 and IFNβ, only one of the two, or neither. Thus, combinations of PRR agonists were found to increase the production of IL-12p70 by human DCs in a synergistic manner, and we identified six PRR agonist combinations that may represent strong adjuvant candidates, in particular for therapeutic cancer vaccines.

• Gudmundsrud, Ruben; Skjånes, Tarjei Hartmann; Gilmour, Brian Christopher; Caponio, Domenica; Lautrup, Sofie Hindkjær & Fang, Fei (2021). Crosstalk among DNA Damage, Mitochondrial Dysfunction, Impaired Mitophagy, Stem Cell Attrition, and Senescence in the Accelerated Ageing Disorder Werner Syndrome. Cytogenetic and Genome Research. ISSN 1424-8581. 161(6-7), p. 297–304. doi: 10.1159/000516386. Full text in Research Archive Show summary

  Werner syndrome (WS) is an accelerated ageing disease caused by multiple mutations in the gene encoding the Werner DNA helicase (WRN). The major clinical features of WS include wrinkles, grey hair, osteoporosis, and metabolic phenomena such as atherosclerosis, diabetes, and fatty liver, and resemble those seen in normal ageing, but occur earlier, in middle age. Defective DNA repair resulting from mutations in WRN explain the majority of the clinical features of WS, but the underlying mechanisms driving the larger metabolic dysfunction remain elusive. Recent studies in animal models of WS and in WS patient cells and blood samples suggest the involvement of impaired mitophagy, NAD<sup>+</sup> depletion, and accumulation of damaged mitochondria in metabolic dysfunction. This mini-review summarizes recent progress in the understanding of the molecular mechanisms of metabolic dysfunction in WS, with the involvement of DNA damage, mitochondrial dysfunction, mitophagy reduction, stem cell impairment, and senescence. Future studies on NAD<sup>+</sup> and mitophagy may shed light on potential therapeutic strategies for the WS patients.

• Fang, Fei; Xie, Chenglong; Schenkel, Joseph A; Wu, Chenkai; Long, Qian & Cui, Honghua [Show all 32 contributors for this article] (2020). A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research, long-term care, policy and social networks. Ageing Research Reviews. ISSN 1568-1637. 64, p. 101174–101174. Full text in Research Archive
• Gilmour, Brian Christopher; Gudmundsrud, Ruben; Frank, Johannes; Hov, Amund; Lautrup, Sofie Hindkjær & Aman, Yahyah [Show all 18 contributors for this article] (2020). Targeting NAD+ in translational research to relieve diseases and conditions of metabolic stress and ageing. Mechanisms of Ageing and Development. ISSN 0047-6374. 186, p. 1–6. doi: 10.1016/j.mad.2020.111208. Full text in Research Archive Show summary

  Nicotinamide adenine dinucleotide (NAD+) plays a fundamental role in life and health through the regulation of energy biogenesis, redox homeostasis, cell metabolism, and the arbitration of cell survival via linkages to apoptosis and autophagic pathways. The importance of NAD+ in ageing and healthy longevity has been revealed from laboratory animal studies and early-stage clinical testing. While basic researchers and clinicians have investigated the molecular mechanisms and translation potential of NAD+, there are still major gaps in applying laboratory science to design the most effective trials. This mini-review was based on the programme and discussions of the 3rd NO-Age Symposium held at the Akershus University Hospital, Norway on the 28th October 2019. This symposium brought together leading basic researchers on NAD+ and clinicians who are leading or are going to perform NAD+ augmentation-related clinical studies. This meeting covered talks about NAD+ synthetic pathways, subcellular homeostasis of NAD+, the benefits of NAD+ augmentation from maternal milk to offspring, current clinical trials of the NAD+ precursor nicotinamide riboside (NR) on Ataxia-Telangiectasia (A-T), Parkinson’s disease (PD), post-sepsis fatigue, as well as other potential NR-based clinical trials. Importantly, a consensus is emerging with respect to the design of clinical trials in order to measure meaningful parameters and ensure safety.

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• Fang, Fei; Bergersen, Linda Hildegard & Gilmour, Brian Christopher (2023). Molecular, Cellular, and Metabolic Fundamentals of Human Aging. Academic Press. ISBN 9780323916172. 246 p. Full text in Research Archive

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• Chan, Hanna; Borowicz, Pawel; Gilmour, Brian Christopher; Stensland, Maria; Garcia-Loza, Ivan & Phuyal, Santosh [Show all 10 contributors for this article] (2026). The TSAd-DOK2 axis regulates CD8+ T cell effector function. Full text in Research Archive
• Borowicz, Pawel; Gilmour, Brian Christopher; Chan, Hanna; Gopalakrishnan, Ramakrishna Prabhu; Peters, Timo & Platzer, Rene [Show all 20 contributors for this article] (2026). Instrinsically disordered insert from SH2D2A rewires CD19 CAR signaling via Tyr290. Full text in Research Archive
• Visser, Johan Georg; Borowicz, Pawel; Chan, Hanna; Hauge, Anette; Kjelstrup, Hanna & Gilmour, Brian Christopher [Show all 7 contributors for this article] (2024). Enhanced analysis of cancer signalling using Lck SH2 domain superbinder. Full text in Research Archive
• Chan, Hanna; Borowicz, Pawel; Gilmour, Brian Christopher; Stensland, Maria; Loza, Ivan Garcia & Phuyal, Santosh [Show all 10 contributors for this article] (2024). Identification of novel interactors of T cell Specific Adaptor protein TSAd - An adaptor molecule with elusive function. Full text in Research Archive
• Borowicz, Pawel; Peters, Timothy J.; Platzer, Rene; Gilmour, Brian Christopher; Seigner, Jacqueline & Darwich, Manal el [Show all 11 contributors for this article] (2024). Chimeric antigen receptors with Lck-adaptors' sequences. Full text in Research Archive
• Gilmour, Brian Christopher; Visser, Johan Georg; Köhn-Luque, Alvaro; Lossius, Andreas & Spurkland, Anne (2024). SH2D2A Is an Indicator of Favourable Prognosis in Bladder Cancer and Is Enriched in Activated Treg Cells. Full text in Research Archive
• Chan, Hanna; Borowicz, Pawel; Gilmour, Brian Christopher; Stensland, Maria; Loza, Ivan Garcia & Phuyal, Santosh [Show all 10 contributors for this article] (2024). Identification of novel interactors of T cell specific adaptor protein TSAd - an adaptor molecule with elusive function. Full text in Research Archive
• Gilmour, Brian Christopher; Chan, Hanna; Borowicz, Pawel; Phuyal, Santosh; Lossius, Andreas & Spurkland, Anne (2023). β2, or not β2? Connecting the Lck-adaptor TSAd to integrin β2 via a combined wet lab & bioinformatic approach. Full text in Research Archive
• Chan, Hanna; Borowicz, Pawel; Kjelstrup, Hanna; Gilmour, Brian Christopher; Loza, Ivan Garcia & Stensland, Maria [Show all 8 contributors for this article] (2022). Novel interaction partners of the SH2 domain in T cell specific adaptor protein (TSAd). Full text in Research Archive
• Gilmour, Brian Christopher; Chan, Hanna; Borowicz, Pawel; Georg, Visser Johan; Lossius, Andreas & Spurkland, Anne (2022). Applying bioinformatics to pick-apart elusive protein functions: Focusing on TSAd/SH2D2A, an immune kinase adaptor. Full text in Research Archive
• Gilmour, Brian Christopher; Chan, Hanna; Borowicz, Pawel; Kjelstrup, Hanna & Spurkland, Anne (2021). Application of bioinformatics to outstanding questions in immunology: TSAd (T cell adapter protein). Full text in Research Archive
• Gilmour, Brian Christopher; Corthay, Alexandre Benoit & Øynebråten, Inger (2019). Optimising the activation of dendritic cells to promote anti-cancer T cell responses. Full text in Research Archive
• Gilmour, Brian Christopher; Spurkland, Anne; Dissen, Erik & Phuyal, Santosh (2024). β2, or not β2: that is the question. Expanding the SH2D2A-interactome to adhesion & β-integrins using a combined bioinformatic & wet-lab approach. Universitetet i Oslo. ISSN 9788234804847. Full text in Research Archive Show summary

  While the functions of many genes are known, others remain unexplored. Adaptor proteins, an under-studied group, lack enzymatic activity but are crucial in forming and modulating signalling complexes. These proteins are difficult to study because their knockout often does not produce a clear phenotype—an “anchor” which can then be used for further study—making further exploration challenging. Adaptor proteins are especially important in immune cells, which rely on complex signalling pathways. SH2D2A (TSAd) is one such adaptor protein that is highly expressed in immune cells. Its exact function is unclear, though it interacts with key kinases like LCK, ITK, and SRC. This study aimed to expand the known interactome of SH2D2A to better understand its role. Initial experiments suggested SH2D2A might interact with the SRC family kinase FYN, but this could not be confirmed under physiological conditions. Further analysis of bulk RNA-seq data from the Cancer Genome Atlas (TCGA) revealed that higher SH2D2A expression in tumours correlates with better prognosis in bladder urothelial cancer (BLCA), an effect associated with FOXP3+ IL2RAhi T regulatory (Treg) cells, which are the main expressors of SH2D2A in the BLCA bladder. This bioinformatic approach could help uncover functions of other immune-related adaptor proteins.

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