Our Research

Development of innovative tools for chromatin biology, gene therapy, and genome evolution studies

🔬 1. Spatio-temporal Chemical and Biological Tools Development

Development and application of spatio-temporal chemical tools to study Chromatinized multi-omics:

1) SiTomics Strategy for Dynamic Histone Modifications

System-wide analysis of dynamic histone modifications in the context of unperturbed chromatin is key to our understanding of the orchestration between metabolic homeostasis and transcriptional regulation in health and disease.

We herein developed a single-site-resolved multi-omics (SiTomics) strategy for systematic mapping of dynamic modifications and subsequent profiling of chromatinized proteome and genome defined by specific chromatin acylations in living cells.

SiTomics offers a platform technology for elucidating the “metabolites-modification-regulation” axis, which is widely applicable for multi-omics profiling and functional dissection of modifications beyond acylations and proteins beyond histones.(Cell, 2023, 186(5), 1066-1085.)

2) Photoaffinity Lysine Analogues for Epigenetic Regulation

Covalent histone modifications, primarily through lysine posttranslational modifications (PTMs), are fundamental epigenetic regulation mechanisms underlying diverse cellular processes.

We herein have developed photoaffinity analogues of crotonyl lysine and unmodified lysine that can be site-specifically incorporated into proteins such as histone H3 protein via the genetic code expansion strategy.

This allowed the investigation of lysine PTM-mediated protein−protein interactions between full-length H3 protein and its epigenetic regulatory effectors in vitro and in living cells.

Such a “dual-functional” photoaffinity lysine analogue can be extended to accommodate additional lysine PTMs other than crotonylation, which may become a powerful toolkit to uncover diverse lysine PTM-mediated histone−effector interactions.(JACS, 2017, 139(19), 6522-6525.)

📄 Recent Representative Work

1. Fangfei Qin#,, Boyuan Li#, Hui Wang, Sihui Ma, Jiaofeng Li, Shanglin Liu, Linghao Kong, Huangtao Zheng, Rongfeng Zhu, Yu Han, Mingdong Yang, Kai Li, Xiong Ji, Peng R. Chen* Linking chromatin acylation mark-defined proteome and genome in living cells. Cell, 2023, 186(5), 1066-1085.

2. Xiao Xie#, Xiao-Meng Li#, Fangfei Qin#, Jianwei Lin, Gong Zhang, Jingyi Zhao, Xiucong Bao, Rongfeng Zhu, Haiping Song, Xiang David Li*, and Peng R. Chen* Genetically encoded photoaffinity histone marks. JACS, 2017, 139(19), 6522-6525.

🧬 2. Genomic Tools Development for Genetic Disease Therapy

Development and application of genomic tools for gene therapy and cell therapy of genetic disease

Zellweger spectrum disorder (ZSD) is caused by biallelic loss-of-function variants in PEX genes required for peroxisome biogenesis, which is critical for normal cellular metabolism and signalling.

The PEX1-p.G843D (c.2528G>A) allele, present in approximately 30% of individuals with ZSD, frequently results in chronic liver disease that can progress to cirrhosis, hepatocellular carcinoma and degraded neurological health.

Here we report the development and application of an adenine base editing strategy to correct an established homozygous Pex1-p.G844D ZSD mouse model that manifests liver pathologies and metabolic dysfunction found in patients.

Genome-wide experimental and computational off-target analyses found minimal off-target editing in the mouse or human genome.

This provides a foundation for developing precision gene correction treatments that address the root cause of a wide range of peroxisomal disorders.(NBE, 2026, DOI: 10.1038/s41551-026-01651-5)

📄 Recent Representative Work

1. Xin D. Gao#, Maximiliano Presa#, Jordyn E. Duby, Jennifer Ryan, Pierre-Alexandre Piec, Alvin Hsu, Samagya Banskota, Allen Yujie Jiang, Lingxiao Chen, Gregory A. Newby, Erminia Di Pietro, Jonathan M. Levy, Bradford H. Steele, Sarah Lecordier, Fangfei Qin, Ann B. Moser, Jun Xie, Guangping Gao, Nancy E. Braverman, Aamir R. Zuberi, Joseph G. Hacia, Cathleen M. Lutz* & David R. Liu* Nature Biomedical Engineering 2026 DOI: 10.1038/s41551-026-01651-5.

2. Xin Gao, Maximiliano Presa, Jordyn Duby, Jennifer Ryan, Pierre-Alexandre Piec, Alvin Hsu, Samagya Banskota, Allen Jiang, Lingxiao Chen, Gregory Newby, Erminia Pietro, Jonathan Levy, Bradford Steele, Sarah Lecordier, Fangfei Qin, Ann Moser, Jun Xie, Guangping Gao, Dr. Nancy Braverman, Aamir Zuberi, Joseph Hacia, Cathleen Lutz, David R. Liu* Rescue of Zellweger Spectrum Disorder in mice and in patient cells by base editing. 28th Annual Meeting of the American Society of Gene & Cell Therapy, New Orleans, LA, USA

🧬 3. Transposon Elements and Genome Evolution

This is an exciting world. We are actively working on them. Publications are underway…