Taisuke Kanaji, MD, PhD - Scripps Research

Research Focus

Platelets contribute not only to hemostasis and thrombosis but also to inflammation and immunity. Over two decades, we have studied platelet generation and activation through the VWF–GPIb–Filamin A axis. We identified an alternative thrombopoiesis pathway, driven by activated tyrosyl-tRNA synthetase (YARS), that compensates for platelet loss under inflammatory stress (Kanaji T et al., PNAS 2018, 115:E8228–E8235). This pathway is especially relevant in severe viral or bacterial infections, such as LCMV, and is mediated by endosomal TLRs and type I interferons (Morodomi Y et al., PNAS 2022, 119:e2212659119). Extending this work to Antisynthetase Syndrome, we found that secretion of the targeted intracellular antigens is enhanced, possibly via autophagy-mediated unconventional secretion, and hypothesize that this aberrant extracellular exposure triggers autoantibody production—a mechanism we are now elucidating.

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Jones, Juli A.; Wei, Na; Cui, Haissi; Shi, Yi; Fu, Guangsen; Rauniyar, Navin; Shapiro, Ryan; Morodomi, Yosuke; Berenst, Nadine; Dumitru, Calin D.; Kanaji, Sachiko; Yates, John R.; Kanaji, Taisuke; Yang, Xiang- L. Nuclear translocation of an aminoacyl-tRNA synthetase may mediate a chronic "integrated stress response". Cell Reports 2023, 42, 112632.
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Kanaji, Sachiko; Chen, Wenqian; Morodomi, Yosuke; Shapiro, Ryan; Kanaji, Taisuke; Yang, Xiang- L. Mechanistic perspectives on anti-aminoacyl-tRNA synthetase syndrome. Trends in Biochemical Sciences 2023, 48, 288-302.
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Kanaji, Taisuke; Morodomi, Yosuke; Kanaji, Sachiko Circulating immune cells with megakaryocyte signature in response to COVID-19 mRNA vaccination. Thrombosis Research 2022, 220, 1-4.
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Morodomi, Yosuke; Kanaji, Sachiko; Sullivan, Brian M.; Zarpellon, Alessandro; Orje, Je N.; Won, Eric; Shapiro, Ryan; Yang, Xiang- L.; Ruf, Wolfram; Schimmel, Paul; Ruggeri, Zaverio M.; Kanaji, Taisuke Inflammatory platelet production stimulated by tyrosyl-tRNA synthetase mimicking viral infection. Proc Natl Acad Sci U S A 2022, 119, e2212659119.
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Kanaji, Sachiko; Morodomi, Yosuke; Weiler, Hartmut; Zarpellon, Alessandro; Montgomery, Robert R R.; Ruggeri, Zaverio M.; Kanaji, Taisuke The impact of aberrant von Willebrand factor-GPIba interaction on megakaryopoiesis and platelets in humanized type 2B von Willebrand disease model mouse. Haematologica 2022, 107, 2133-2143.
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Nakamura, Takayuki; Morodomi, Yosuke; Kanaji, Sachiko; Okamura, Takashi; Nagafugi, Koji; Kanaji, Taisuke Detection of anti-GPIba autoantibodies in a case of immune thrombocytopenia following COVID-19 vaccination. Thrombosis Research 2022, 209, 80-83.
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