Research Focus

Elucidation of Immune Cell Activation Mechanisms

Aberrant activation of T cells plays a critical role in cancer progression as well as in the development and relapse of autoimmune diseases. Although the mechanisms underlying T cell activation have been intensively studied over many years, precise and flexible control of T cell function remains challenging, highlighting the need to uncover novel regulatory principles. To this end, it is essential to understand T cell regulatory mechanisms from new perspectives and translate these insights into innovative therapeutic strategies.

In this project, we focus on the integrated stress response (ISR) pathway, a cellular mechanism that modulates cellular function in response to stress, and aim to elucidate regulatory mechanisms governing immune cells, including T cells. The ISR has been shown to regulate the activation of memory T cells (Asada et al., Nature Immunology, 2025); however, it may also be involved in other aspects of T cell function and broader immune cell regulation, warranting further investigation.

To address this, we will establish state-of-the-art comprehensive analytical platforms and genetic manipulation systems to systematically analyze the role of the ISR in T cells under pathological conditions such as cancer and autoimmune diseases. In addition to T cells, we will perform integrated analyses of other immune cell populations to achieve a comprehensive understanding of immune regulation.

Disease Stratification and Identification of Novel Pathological Mechanisms

While standard therapies are administered for many diseases, patients often show heterogeneous responses, with some failing to respond to treatment. Elucidating why certain patients do not respond to therapy will not only deepen our understanding of disease pathogenesis but also improve therapeutic success rates.

In this project, we aim to uncover the molecular mechanisms underlying treatment resistance using comprehensive analytical approaches in immune-related diseases, including nephritis, vasculitis, systemic lupus erythematosus (SLE), as well as cancer. Furthermore, based on these insights, we seek to establish disease stratification frameworks and identify novel therapeutic targets.

Members

Professors

Selected Publications

Wang H, Engesser J, Khatri R, Schaub DP, Paust HJ, Sultana Z, Jauch-Speer SL, Peters A, Kaffke A, Bonn S, Huber TB, Mittrücker HW, Krebs CF, Panzer U, Asada N. Type I interferon drives T cell cytotoxicity by upregulation of interferon regulatory factor 7 in autoimmune kidney diseases in mice. Nat Commun. 2025;16(1):4686. (Corresponding author) DOI: 10.1038/s41467-025-59819-7

Asada N, Ginsberg P, Paust HJ, Song N, Riedel JH, Turner JE, Peters A, Kaffke A, Engesser J, Wang H, Zhao Y, Khatri R, Gild P, Dahlem R, Diercks BP, Das S, Ignatova Z, Huber TB, Prinz I, Gagliani N, Mittrücker HW, Krebs CF, Panzer U. The integrated stress response pathway controls cytokine production in tissue-resident memory CD4+ T cells. Nat Immunol. 2025;26(4):557–566. DOI: 10.1038/s41590-025-02105-x

Asada N, Krebs CF, Panzer U. Miniproteins may have a big impact: new therapeutics for autoimmune diseases and beyond. Signal Transduct Target Ther. 2024;9(1):298. DOI: 10.1038/s41392-024-02010-z

Engesser J, Wang H, Kapffer S, Kaffke A, Peters A, Paust HJ, Geissen M, Krebs CF, Panzer U, Asada N. S1PR1 mediates Th17 cell migration from the thymus to the skin in health and disease. Front Immunol. 2024;15:1473130. (Corresponding author) DOI: 10.3389/fimmu.2024.1473130

Ginsberg P, Panzer U, Asada N. Tissue-resident memory T cells in renal autoimmune diseases. Front Immunol. 2023:14:1111521. (Corresponding author) DOI: 10.3389/fimmu.2023.1111521

Asada N*, Ginsberg P*, Gagliani N, Mittrücker H, Panzer U. Tissue-resident memory T cells in the kidney. Semin Immunopathol. 2022 Nov;44(6):801-811. (* equally contributed) DOI: 10.1007/s00281-022-00927-7

Ohnishi T*, Asada N*, Furuichi M, Sekiguchi S, Awazu M, Hori N, I Kamimaki. A novel screening method for pediatric urinary tract infection using ordinary diapers. Sci Rep. 2020;10(1):19342. (* equally contributed. Asada N, corresponding author) DOI: 10.1038/s41598-020-76405-7

Asada N. Tubular immaturity causes erythropoietin-deficiency anemia of prematurity in preterm neonates. Sci Rep. 2018;8(1):4448. DOI: 10.1038/s41598-018-22791-y

Asada N, Tsukahara T, Furuhata M, Matsuda D, Noda S, Naganuma K, Hashiguchi A, Awazu M. Polycythemia, capillary rarefaction, and focal glomerulosclerosis in two adolescents born extremely low birth weight and premature. Pediatr Nephrol. 2017;32(7): 1275-1278. (Corresponding author) DOI: 10.1007/s00467-017-3654-z

Asada N, Kato I, Daifu T, Umeda K, Hiramatsu H, Okamoto T, Toguchida J, Yamawaki S, Yoshikawa K, Adachi S, Heike T, Watanabe K. Good Response to Chemotherapy Spares Irradiation for Extrarenal Rhabdoid Tumor Conferring Better Activities of Daily Living. J Pediatr Hematol Oncol. 2015;37(1):e57-9. DOI: 10.1097/MPH.0000000000000150

Asada N, Takase M, Nakamura J, Oguchi A, Asada M, Suzuki N, Yamamura K, Nagaoshi N, Shibata S, Tata Nageswara Rao, Hans Joerg Fehling, Fukatsu A, Minegishi N, Kita T, Kimura T, Okano H, Yamamoto M, and Yanagita M. Dysfunction of fibroblasts of extra- renal origin underlies renal fibrosis and renal anemia in mice. J Clin Invest. 2011;121(10): 3981-90. DOI: 10.1172/JCI57301

Recruitment & Contact

We are permanently recruiting highly motivated students, postdoctoral fellows, and technical staff regardless of previous scientific backgrounds.

Please contact us using CCII’s contact form or by directly sending an email to recruit_ccii@mail2.adm.kyoto-u.ac.jp. Please indicate in which position and subject area you are interested in and that your inquiry is about our research division.