Jong-Sun Lee, PhD, MS

Jong-Sun “Sun” Lee, PhD, is an Assistant Professor in the Biochemistry and Molecular Biology discipline and a member of the Center for Genetic Diseases at Rosalind Franklin University of Medicine & Science. Dr. Lee studies how long non-coding RNAs (lncRNAs) regulate ribosome biogenesis and translational control in cancer, with a focus on kidney and colorectal tumors. He received a BS in Biology (2008) and an MS in Chemistry (2010) from Baylor University, a PhD in Biomedical Science from Mayo Clinic (2016), and completed postdoctoral training at Columbia University and UT Southwestern Medical Center, where he later served as Assistant Instructor.  

His research integrates CRISPR-based functional genomics with RNA biochemistry to discover cancer-relevant lncRNAs and define their mechanisms, including ultraconserved snoRNA-like elements that influence 60S ribosomal subunit maturation. Dr. Lee’s work has been recognized with a Department of Defense Postdoctoral Fellowship (2021–2024) and the Oligonucleotide Therapeutics Society Paper of the Year Award (2020). His lab also explores RNA-targeting therapeutics (e.g., antisense oligonucleotides), aiming to translate basic RNA biology into new strategies for cancer detection and treatment.

Research

We study how long non-coding RNAs (lncRNAs) govern ribosome biogenesis and how these pathways shape human disease, including cancer and aging. We combine CRISPRi/a functional genomics with RNA biochemistry, interaction mapping, and quantitative imaging and subcellular/biochemical fractionation to track localization, nucleolar phenotypes, and ribosome-assembly states. These approaches enable us to identify lncRNAs that regulate rDNA transcription, pre-rRNA processing, and ribosomal subunit maturation. Our recent work uncovered ultraconserved, snoRNA-like elements embedded within lncRNAs that bind pre-rRNA and recruit factors such as eIF6, linking RNA architecture to ribosome assembly and tumor fitness. Building on these mechanisms, we develop RNA-targeting therapeutics, especially antisense oligonucleotides (ASOs) for kidney and colorectal cancers. Our goal is to define RNA-guided checkpoints in ribosome biogenesis and translate them into precise diagnostic and therapeutic strategies, from discovery through mechanism to preclinical proof-of-concept.

Publications

• Lee, J.-S., Dan, T., Zhang, H., Cheng, Y., Rehfeld, F., Brugarolas, J., and Mendell, J.T. (2025). An ultraconserved snoRNA-like element in long noncoding RNA CRNDE promotes ribosome biogenesis and cell proliferation. Molecular Cell. 85 (8), pp. 1543-1560.e10. DOI: 10.1016/j.molcel.2025.03.006
• Cheng, Y., Wang, S., Zhang, H., Lee, J.-S., Ni, C., Guo, J., Chen, E., Wang, S., Acharya, A., Chang, T.-C., et al. (2024). A non-canonical role for a small nucleolar RNA in ribosome biogenesis and senescence. Cell 187, 1-20. DOI: 10.1016/j.cell.2024.06.019
• Lee, J.-S., Mendell, J.T. Antisense-Mediated Transcript Knockdown Triggers Premature Transcription Termination (2020) Molecular Cell, 77 (5), pp. 1044-1054.e3. DOI: 10.1016/j.molcel.2019.12.011
  *The importance of this study has been highlighted in Nature Reviews Genetics and recognized by the Oligonucleotide Therapeutics Society, which highlighted the study as “the Paper of the Year” in 2020.
• Lee, J.-S., Mo, Y., Gan, H., Burgess, R.J., Baker, D.J., van Deursen, J.M., Zhang, Z. Pak2 kinase promotes cellular senescence and organismal aging (2019) Proceedings of the National Academy of Sciences, 116 (27), pp. 13311-13319. DOI: 10.1073/pnas.1903847116
• Lee, J.-S., Zhang, Z. O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence (2016) Proceedings of the National Academy of Sciences, 113 (23), pp. E3213-E3220. DOI: 10.1073/pnas.1600509113
• Park, H.-C., Sung, S.-R., Lim, S.M., Lee, J.-S., Kim, S.-K., Yoon, M.-Y. Proteolytic assay-based screening identifies a potent inhibitor of anthrax lethal factor (2012) Microbial Pathogenesis, 53 (2), pp. 109-112. DOI: 10.1016/j.micpath.2012.04.004
• Kim, S.G., Chung, J.-S., Sutton, R.B., Lee, J.-S., López-Maury, L., Lee, S.Y., Florencio, F.J., Lin, T., Zabet-Moghaddam, M., Wood, M.J., Nayak, K., Madem, V., Tripathy, J.N., Kim, S.-K., Knaff, D.B. Redox, mutagenic and structural studies of the glutaredoxin/arsenate reductase couple from the cyanobacterium Synechocystis sp. PCC 6803 (2012) Biochimica et Biophysica Acta - Proteins and Proteomics, 1824 (2), pp. 392-403. DOI: 10.1016/j.bbapap.2011.10.012
• Schlesinger, S.R., Kim, S.G., Lee, J.-S., Kim, S.-K. Purification development and characterization of the zinc-dependent metallo-β-lactamase from Bacillus anthracis (2011) Biotechnology Letters, 33 (7), pp. 1417-1422. DOI: 10.1007/s10529-011-0569-9
• Lee, J.-S., White, E., Kim, S.G., Schlesinger, S.R., Lee, S.Y., Kim, S.-K. Discovery of a novel adenosine 5′-phosphosulfate (APS) reductase from the methanarcheon Methanocaldococcus jannaschii (2011) Process Biochemistry, 46 (1), pp. 154-161. DOI:10.1016/j.procbio.2010.08.004
• Lee, J.-S., White, E., Kim, S.G., Kim, S.-K. Virtual screening of penicillin-derived inhibitors for the metallo-β-lactamase from Bacillus cereus (2010) Bulletin of the Korean Chemical Society, 31 (12), pp. 3644-3652. DOI: 10.5012/bkcs.2010.31.12.3644
• Kim, S.G., Chi, Y.H., Lee, J.-S., Schlesinger, S.R., Zabet-Moghaddam, M., Chung, J.-S., Knaff, D.B., Kim, S.T., Lee, S.Y., Kim, S.-K. Redox properties of a thioredoxin-like Arabidopsis protein, AtTDX (2010) Biochimica et Biophysica Acta - Proteins and Proteomics, 1804 (12), pp. 2213-2221. DOI: 10.1016/j.bbapap.2010.09.005

Research Programs

• LncRNAs and ribosome biogenesis:
  We uncover how non-coding RNAs control ribosome production and fuel tumor growth.
• Ultraconserved RNA modules:
  We define snoRNA-like “switches” embedded in lncRNAs that direct ribosomal subunit assembly.
• DNA transcription control:
  We map how non-coding RNAs regulate RNA Polymerase I and nucleolar chromatin to set ribosome output.
• RNA-targeting therapeutics:
  We design antisense oligonucleotides to disable oncogenic lncRNAs and test them in preclinical cancer models.