YU Zutao

RESEARCH

More than 7,000 orphan diseases have been reported, with approximately 80% caused by mutations in a single gene. Beyond rare disorders, monogenic defects also contribute to common conditions such as familial hypercholesterolemia, cystic fibrosis, and certain forms of diabetes and cancer. Growing evidence demonstrates that selectively correcting key disease-driving genes can offer profound therapeutic benefits. However, clinical translation remains limited due to challenges such as undruggable protein targets, acquired drug resistance, and a lack of efficient strategies for gene-specific intervention. To address these unmet needs, our lab develops gene-selective chemical approaches that directly target DNA and RNA to modulate transcription and translation, offering new avenues for precision therapeutics. Our research is guided by the following key questions:

Which genes drive disease?

How can we control gene expression by chemically targeting DNA and RNA?

How can innovative designs and strategies enhance nucleic acid binders?

By designing novel nucleic acid binders—such as small molecules and antisense oligonucleotides—we aim to achieve selective gene regulation, paving the way for rational drug discovery. Leveraging advanced chemical design, structural biology, next-generation sequencing technologies, and computational approaches, we strive to validate DNA and RNA as precise, druggable therapeutic targets. Our research ultimately seeks to pioneer transcriptome- and genome-targeting strategies, enabling breakthroughs in the treatment of complex diseases such as cancer, infectious diseases, and neurodegenerative disorders.

For more information, please visit our lab website: www.yucleiclab.com and https://scholar.google.com/citations?hl=en&user=U0uXqjUAAAAJ&view_op=list_works&sortby=pubdate.

Selected publications:

Zhang X, Dhir S, Melidis L, Chen Y, Yu Zutao, Simeone A, Spiegel J, Adhikari S, & Balasubramanian S. (2025). Optical control of gene expression using a DNA G-quadruplex targeting reversible photoswitch. Nat. Chem. https://doi.org/10.1038/s41557-025-01792-1 

Esain-Garcia I, Kirchner A,  …, Yu Zutao (7^th), …, Balasubramanian S. (2024) G-quadruplex DNA structure is a positive regulator of MYC transcription, PNAS, 121:e2320240121.

Yu Zutao¹, Spiegel J¹, Melidis L, Hui W.W.I, Zhang X, Radzevičius A, Balasubramanian S* (2023) Chem-map: Profiling drug binding to chromatin in cells. Nat. Biotechnol., 41:1265. F1000 recommended.

Yu Zutao, Ai M, Samanta SK, Hashiya F, Taniguchi J, Asamitsu S, Ikeda S, Hashiya K, Bando T, Pandian GN*, Isaacs L*, Sugiyama H* (2020) A synthetic transcription factor pair mimic for precise recruitment of an epigenetic modifier to the targeted DNA locus, Chem. Commun., 56:2296.

Sahayasheela VJ, Yu Zutao, Hidaka T, Pandian GN, Sugiyama H (2023) Mitochondria and G-quadruplex evolution: an intertwined relationship, Trends Genet., 39:15

Sahayasheela VJ, Yu Zutao, Hirose Y, Pandian GN, Bando T, Sugiyama H (2022) Inhibition of GLI-Mediated Transcription by Cyclic Pyrrole-Imidazole Polyamide in Cancer Stem Cells, Bull. Chem. Soc. Jpn., 95:693.

Yu Zutao, Pandian GN*, Hidaka T, Sugiyama H* (2019) Therapeutic gene regulation using pyrrole-imidazole polyamides, Adv. Drug Deliv. Rev., 147:66.

Yu Zutao, Chen Z, Su Q, Ye S, Yuan H, Kuai M, Lv M, Tu Z, Yang X, Liu R, Hu G, Li Q* (2019) Dual inhibitors of RAF-MEK-ERK and PI3K-PDK1-AKT pathways: Design, synthesis, and preliminary anticancer activity studies of 3-substituted-5-(phenylamino) indolone derivatives, Bioorg. Med. Chem., 27:944.

Yu Zutao, Guo C, Wei Y, Hashiya K, Bando T, Sugiyama H* (2018) Pip-HoGu: An Artificial Assembly with Cooperative DNA Recognition Capable of Mimicking Transcription Factor Pairs,         J. Am. Chem. Soc., 140:2426.

Yu Zutao, Hsieh WC, Asamitsu S, Hashiya K, Bando T, Ly DH*, Sugiyama H* (2018) Orthogonal gammaPNA Dimerization Domains Empower DNA Binders with Cooperativity and Versatility Mimicking that of Transcription Factor Pairs, Chem. Eur. J., 24:14183.

Yu Zutao, Taniguchi J, Wei Y, Pandian GN, Hashiya K, Bando T, Sugiyama H* (2017) Antiproliferative and apoptotic activities of sequence-specific histone acetyltransferase inhibitors, Eur. J. Med. Chem., 138:320.

Patents:

Yu Z, Spegiel J, Balasubramanian S (2022) Methods for mapping compound binding sites. United Kingdom (GB). Priority No. GB2209984.0 (07 July 2022), GB2218733.0 (13 Dec 2022)

Hsieh WC, Sugiyama H, Yu Z (2020) Orthogonal gamma-PNA dimerization domains empowering DNA binders with cooperativity and versatility mimicking that of the transcription factor pairs. US Patent No. 16/676,613

Li Q, Hu G, Jiang D, YU Z (2019) The synthesis and application of di-substituted indole-2(1H)-one derivatives. China Patent No. CN106316923A