Faculty Members

•  ljjuan1025@gmail.com
•  Line ID: lijungjuan
•  ORCID
•  02-27871234 (O)
   02-27898775 (Lab)

RESEARCH INTERESTS

Transcriptional and Epigenetic Regulation in Development and Disease

Juan laboratory is interested in transcriptional and epigenetic regulation in development and disease. We used to study important epigenetic regulators which control viral replication and tumor malignancy. In recent years, we have been focusing on protein N-a-acetylation. We found that the protein N-a-acetyltransferase Naa10p is important for global DNA methylation, genomic imprinting, embryonic development and its overexpression can cause cancer and obesity.

Major Contribution

1. Viral proteins inhibited host histone modifying enzyme activity and hijacked host chromatin assembly factor for viral replication (EMBO 2004, JBC 2009, Cell Res 2011, Oncogene 2012)

2. Histone demethylase RBP2 recognized specific DNA sequences (Nat Struc Mol Biol 2008, GRC major discovery, highlighted by Academia Sinica and A-IMBN) and promoted lung tumor malignancy depending on its enzymatic and DNA binding activities (Cancer Res 2013)

3. O-GlcNAc transferase (OGT) glycosylated and stabilized histone methyltransferase EZH2 for tumor suppressor gene silencing (PNAS 2014, GRC major discovery)

4. DNA demethylation enzyme TET1 was a tumor suppressor by activating tissue inhibitors of matrix metalloproteinases (Best 5 Article in Cell Reports 2012, highlighted by Cell and Cell Reports websites, GRC major discovery)

5. The N-a-acetyltransferase Naa10p promoted lung tumorigenesis (J Clin Invest 2010, GRC major discovery, highlighted by Academia Sinica and A-IMBN) and maintained genomic imprinting (Mol Cell 2017, GRC Major Discovery, highlighted by Academia Sinica) by facilitating DNA methyltransferase 1 function, and caused obesity by inhibiting thermogenic gene expression and beige adipogenesis (Mol Cell 2019, highlighted by Nat Stru Mol Biol, Academia Sinica Major Discovery)

Current Focus

1. N-a-acetyltransferase Naa10p in neuron function. Naa10p is enriched in the hippocampus. Its mutations in human cause developmental delay which includes intellectual disability and autism. The underlying mechanim by which Naa10p regulates neuron function is iunder investigation using hippocampus-specific Naa10p KO mice.

2. Histone N-a-acetylation in development and cancer. The N-a-acetyltransferase Naa40p only has two substrates: histone H2A and H4. Naa40p has been implicated in aging and cancer. H2A/H4-N-a-acetylation is conserved and prevalent. However, the function is unknown.

3. Epigenetic regulation during adult neural stem cell aging. Adult neurogenesis is likely the key to understand aging and neurodegenerative diseases. Adult neurogenesis is known to decrease with age. Epigenetic alteration has been implicated in adult neural stem cell aging with unknown mechanisms.

Student/RA/Postdoc Wanted