Stanford Department of Medicine reposted this
We’re thrilled to announce our latest publication, “CRISPRi/a screens in human iPSC-cardiomyocytes identify glycolytic activation as a druggable target for doxorubicin-induced cardiotoxicity,” now published in Cell Stem Cell! 🎉 Check out the full article here: https://lnkd.in/gdWbzBi6 Stanford News Center story here: https://lnkd.in/gC3T3Bwu Congratulations to first author, Chun Liu, who recently joined the Medical College of Wisconsin, and to our outstanding collaborators, including Lei (Stanley) Qi from the Stanford University Department of Bioengineering, and team members from the Stanford Cardiovascular Institute, City of Hope, University of California, Davis, and University of North Texas: Mengcheng Shen, Yanxia Liu, Amit Manhas, Ph.D., Shane R. Zhao, Mao Zhang, Nadjet Belbachir, Joe Z. Zhang, Arianne Caudal, Masataka Nishiga, Dilip Thomas, Angela Zhang, Huaxiao 'Adam' Yang, Yang Zhou, Mohamed Ameen, Nazish Sayed, MD PhD, and June-Wha Rhee. A special shout-out to Greenstone Biosciences for invaluable contributions in molecular docking and drug candidate identification. Why does this research matter? Doxorubicin is a powerful chemotherapy agent widely used to treat various cancers, but its life-threatening cardiotoxic side effects limit its broader application. By leveraging CRISPR interference and activation (CRISPRi/a) screens in human induced pluripotent stem cell-derived cardiomyocytes, we identified several novel genes, including carbonic anhydrase 12 (CA12), as druggable targets to mitigate these effects. Our findings showed that inhibiting CA12 protects heart cells from doxorubicin-induced damage without compromising the drug’s anti-cancer efficacy. These results were validated using engineered heart tissues derived from iPSCs and animal models. Broad Implications: Our paper offers a promising therapeutic strategy to mitigate the cardiotoxic effects of doxorubicin, potentially improving the quality of life for countless cancer patients. Furthermore, our work highlights an integrated drug discovery platform combining CRISPR screens with human iPSC models. This innovative approach not only identifies novel drug targets like CA12 but also accelerates drug discovery, enabling the development of faster, more effective therapies with minimal off-target toxicity.