Li-Jung Juan, Ph.D.
Seminar Information
Protein N-terminal α-acetylation is one of the most abundant protein modifications in eukaryotic cells, yet its biological significance has remained remarkably underexplored. Our work reveals that this modification is not merely a constitutive co-translational event, but a critical regulatory mechanism linking chromatin control, development, and human disease.
We have established N-a-acetyltransferase 10 (NAA10) as a key regulator of epigenetics and neural development. NAA10 controls DNA methyltransferase 1 (DNMT1)-dependent DNA methylation and genomic imprinting through acetylation-independent mechanisms, while regulating neuronal morphogenesis and neural tube development through its acetyltransferase activity. These findings have direct clinical relevance: pathogenic NAA10 mutations cause NAA10-related developmental disorders, including Ogden syndrome, providing human genetic evidence that disruption of N-aacetylation can lead to severe neurodevelopmental disease.
I will then present our recent work on NAA40, the highly selective N-terminal acetyltransferase for histones H2A and H4. We find that NAA40 controls epigenetic programs in embryonic stem cells and is essential for normal spermatogenesis and male fertility in vivo. Importantly, NAA40 expression is reduced in human teratozoospermia, linking our mechanistic and mouse studies to human male infertility.
Together, these studies uncover N-terminal a-acetylation as a previously underappreciated layer of epigenetic regulation and establish NAA10 and NAA40 as critical links between protein modification, developmental programs, and human disease.
Li-Jung Juan, PhD, a Professor and Research Fellow of the Genomics Research Center, Academia Sinica, Taipei, Taiwan ROC, is interested in transcriptional and epigenetic regulation in development and disease. She received Ph.D. degree from Penn State University in 1996 with Jerry Workman. In 1997, she became a distinguished postdoctoral fellow at National Health Research Institutes (NHRI) in Taiwan and subsequently an Assistant Investigator of NHRI in 2000. In 2006, Dr. Juan moved to Genomics Research Center, Academia Sinica. Dr. Juan is also an Adjunct Professor at Institute of Molecular Medicine, College of Medicine, National Taiwan University.
One of Dr. Juan’s research focuses has been the use of whole-body and tissue-specific knockout mouse models to investigate the roles of N-terminal a-acetyltransferases, such as NAA10 and NAA40, in epigenetic regulation, development, and disease. The Juan Lab reported that Naa10 is important for global DNA methylation, genomic imprinting, embryonic development (Mol Cell 2017) and hippocampal neuronal function (eLife 2024). In addition, Naa10 overexpression can cause cancer (J Clin Invest 2010) and obesity (Mol Cell 2019, News and Views in Nat Struct Mol Biol). The Juan Lab is currently studying the functions of the abundant and conserved histone N-α-acetylation mediated by Naa40 on H2A and H4. Her works were published in journals including Mol Cell, Nat Struct Mol Biol, J Clin Invest, PNAS, EMBO, Cancer Res, etc.
Dr. Juan has received the Academia Sinica Career Development Award, TienTe Lee Biomedical Young Investigator Award, the Academia Sinica Investigator Award (twice), the YZ Hsu Science and Technology Paper Award, the Ministry of Science and Technology (MOST) Outstanding Research Award, and the Outstanding Scholar Award of the Foundation for the Advancement of Outstanding Scholarship.
Dr. Juan has also contributed to the scientific community by serving on the International Scientific Committee of the Asian Conference on Transcription (ACT) from 2002 to 2011 and as an international organizer of the Asia Epigenome Alliance from 2009 to 2020. Dr. Juan is the founding President (2023-2025) and Executive Director (2025-present) of the Taiwan Epigenetics Society.