PO.PR02.02 · 预防研究

Predicting and preventing cancer stemness in low Earth orbit

编号 7631 展板 18 时间 4/22 09:00–12:00 区域 Section 36 主讲 Jessica Pham

分会场 Cancer and Cancer Related Alterations, Detection Approaches, and Molecular Characterization

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作者与单位

Jessica Pham¹, Wenxue Ma¹, Claire Engstrom¹, Patrick Chang², Shuvro P. Nandi³, Inge van der Werf¹, Emma Klacking¹, Teresa Sposito¹, Kendale Wirtjes¹, Thomas Frias¹, Antonio Ruiz¹, Jane Isquith², Luisa Ladel¹, Christina N. Wu¹, Jana Stoudemire², Pinar Mesci⁴, Kay T. Yeung⁵, Rebecca A. Shatsky⁵, Anna A. Khachatrian⁶, James J. La Clair⁷, Michael D. Burkart⁷, Peggy Wentworth², Curtis L. Scribner⁸, Sheldon R. Morris², Thomas Whisenant⁹, Karla Mack², Ludmil B. Alexandrov¹⁰, Catriona H. M. Jamieson²

¹Department of Medicine, Division of Regenerative Medicine, UC San Diego, La Jolla, CA,²Sanford Stem Cell Institute, UC San Diego, La Jolla, CA,³Department of Cellular and Molecular Medicine, Department of Bioengineering, UC San Diego, La Jolla, CA,⁴Axiom Space, Houston, TX,⁵Department of Medicine, UC San Diego, La Jolla, CA,⁶Scripps Health, La Jolla, CA,⁷Department of Chemistry and Biochemistry, UC San Diego, La Jolla, CA,⁸Aspera Biomedicines, La Jolla, CA,⁹Center for Computational Biology and Bioinformatics, UC San Diego, La Jolla, CA,¹⁰Sanford Stem Cell Institute, Dept. of Cellular and Molecular Medicine, Depart. of Bioengineering, UC San Diego, La Jolla, CA

摘要 Abstract

Cancer stemness properties, including enhanced survival, malignant regeneration, telomere deregulation, genomic and epitranscriptomic instability, fuel metastases, and have been linked to stress, retrotransposon and inflammatory cytokine activation, which can occur in low earth orbit (LEO). In NASA Axiom 1, 2 and 3 missions to the ISS, confocal imaging, WGS, RNA-seq and scRNA-seq of lentiviral FUCCI2BL cell cycle and ADAR1-GFP reporter transduced erythroleukemia (TF-1a), colorectal (Caco-2) and metastatic breast cancer (MBC; MDA-MB-231 and patient samples) revealed proliferation, significant genomic instability, HERV and LINE-1 retrotransposon deregulation, and APOBEC3C and ADAR1 activation. Moreover, in Axiom 2 and 3 missions with ADAR1-reporter expressing MBC organoids and in humanized MBC mouse models, an ADAR1p150 splicing modulator, rebecsinib (IND 153126), prevented tumor propagation. Thus, cancer studies in LEO may accelerate the development of innovative cancer therapeutics and countermeasures for long-term spaceflight.

利益披露 Disclosure

J. Pham, None.. W. Ma, None.. C. Engstrom, None. P. Chang, Aspera Biomedicines Independent Contractor. S. P. Nandi, None.. I. van der Werf, None.. E. Klacking, None.. T. Sposito, None.. K. Wirtjes, None.. T. Frias, None.. A. Ruiz, None.. J. Isquith, None.. L. Ladel, None.. C. N. Wu, None.. J. Stoudemire, None. P. Mesci, Axiom Space Employment. K. T. Yeung, None.. R. A. Shatsky, None.. A. A. Khachatrian, None. J. J. La Clair, Aspera Biomedicines Employment. M. D. Burkart, Aspera Biomedicines Employment. P. Wentworth, Aspera Biomedicines Employment. C. L. Scribner, Aspera Biomedicines Employment. S. R. Morris, Aspera Biomedicines Co-Founder. T. Whisenant, None. K. Mack, Aspera Biomedicines Employment. L. B. Alexandrov, Acturion Employment. C. H. M. Jamieson, Aspera Biomedicines Co-Founder. Impact Biomedicines Co-Founder. Forty Seven Inc Royalties.

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