Robert Tsai, MD, PhD

Biography

Education and Training

1981-1988       National Taiwan University, M.D.
1988-1991       National Taiwan University Hospital, Neurology Residency
1991-1996       Johns Hopkins University School of Medicine, Ph.D.
1996-1997       Johns Hopkins University School of Medicine, Howard Hughes Associate
1997-2003       NIH/NINDS, Research Associate

Research Interests

The development of my program follows two overarching research directions: one in basic science and the other in translational medicine. On the basic research front, my laboratory is focused on understanding the molecular mechanism that drives the self-renewal of stem cells and cancer cells and their biological importance in tissue regeneration (i.e., liver), premature aging, as well as cancer development, prevention, and treatment. We employ a wide variety of biological platforms, including molecular interventions, primary cells, cell line models, animal models (mouse and rat), clinical samples, and genome-wide data analysis to study two chromatin-modifying mechanisms in cancer and aging. The first mechanism involves a family of nucleolar GTPases, one of which, nucleostemin (NS), confers a unique chromatin state in stem/cancer cells critical for maintaining the integrity of their replicating genome. The second mechanism is conferred by novel DNA methylation sites that drive the progression of premalignant lesions to cancers in the liver or oral mucosa or the age-dependent decline in liver regeneration. On the translational research front, my laboratory is currently focused on three projects. The first project is to develop and commercialize a novel 3-D-printed mucoadhesive patch to eradicate oral precancerous lesions (i.e., leukoplakia) for oral cancer prevention with a high lesion-specific efficacy and low systemic toxicities. The second project is to create new diagnostic models based on changes in the DNA methylation pattern to predict the risk of liver and oral precancerous lesions in developing into cancers. The third project is to determine the efficacy of a new class of nanomedicine in treating glioblastoma multiforme using orthotopic mouse brain tumor models. The long-term goal of our translational programs is to take those products to clinical applications.

Selected Publications

1. Tsai, R.YL. and Reed, R.R.* (1997) Cloning and Functional Characterization of Roaz, a Zinc Finger Protein that Interacts with O/E‑1 to Regulates Gene Expression: Implications for Olfactory Neuronal Development. J Neurosci. Vol. 17. No. 11. p4159-4169. PMID: 9151733
2. Tsai, R.YL. and Reed, R.R.* (1998) Identification of DNA Recognition Sequences and Protein Interaction Domains of the Multiple-Zn-Finger Protein, Roaz. Mol Cell Biol. Vol. 18. No. 11. p6447‑6456. PMID: 9774661
3. Tsai, R.YL. and McKay, R.DG.* (2000) Cell Contact Regulates Fate Choice by Cortical Stem Cells. J Neurosci. Vol. 20. No. 10. p3725-3735. PMID: 10804214
4. Tsai, R.YL.and McKay, R.DG* (2002) A Nucleolar Mechanism Controlling Cell Proliferation in Stem Cells and Cancer Cells. Genes Dev. Vol 16. No 23. p2991-3003. PMID: 12464630
5. Tsai, R. YL.*and McKay, R.DG (2005) A Multistep, GTP-driven Mechanism Controlling the Dynamic Cycling of Nucleostemin. J Cell Biol. Vol. 168. No. 1. p179-184. PMID: 15657390
6. Zhu, Q., Yasumoto, H., and Tsai, R. YL.*(2006) Nucleostemin Delays Cellular Senescence and Negatively Regulates TRF1 Protein Stability. Mol Cell Biol. Vol. 24. No. 26. p9279-9290. PMID: 17000763
7. Meng, L., Lin, T., and Tsai, R.YL.* (2008) Nucleoplasmic Mobilization of Nucleostemin Stabilizes MDM2 and Promotes G2-M Progression and Cell Survival. J Cell Sci. Vol. 121. No. 24. p4037-4046. PMID: 19033382
8. Zhu, Q., Meng, L., Hsu, J.K., Lin, T., Teishima, J., and Tsai, R.YL.* (2009) GNL3L Stabilizes the TRF1 Complex and Promotes Mitotic Transition. J Cell Biol. Vol. 185. No. 5. p827-839. PMID: 19487455
9. Lin, T., Meng, L., Li, Y., and Tsai, R.YL.*(2010) Tumor-Initiating Function of Nucleostemin-Enriched Mammary Tumor Cells. Cancer Res. Vol. 70. No. 22. p9444-9452. PMID: 21045149
10. Hsu, J.K., Lin, T., and Tsai, R.YL.* (2012) Nucleostemin Prevents Telomere Damage by Promoting PML-IV Recruitment to SUMOylated TRF1. J Cell Biol. 197. No. 5. p613-624. PMID: 22641345
11. Meng, L., Lin, T., Peng, G., Hsu, J., Lee S., Lin, SY., and Tsai, R.YL.* (2013) Nucleostemin Deletion Reveals An Essential Mechanism That Maintains The Genomic Stability of Stem and Progenitor cells. Proc Natl Acad Sci USA. Vol. 110. No. 28. p11415-11420. PMID: 23798389
12. Lin, T., Ibrahim, W., Peng, C-Y., Finegold, M.J., and Tsai, R.YL.*(2013) A Novel Role of Nucleostemin in Maintaining the Genome Integrity of Dividing Hepatocytes during Mouse Liver Development and Regeneration. Hepatology. Vol. 58. No. 6. p2176-2187. PMID: 23813570
13. Lin, T., Meng, L., Lin, T-C., Wu, L.J., Pederson, T., Tsai, R.YL.*(2014) Nucleostemin and GNL3L Exercise Distinct Functions in Genome Protection and Ribosome Synthesis, Respectively. J Cell Sci. Vol. 127. No. 10. p2302-2312. PMID: 24610951
14. Huang, G., Meng, L., and Tsai, R.YL.* (2015) p53 Configures The G2/M Response of Nucleostemin-Deficient Cells. Cell Death Discov. 1. e15060. PMID: 26835157
15. Tsai, R.YL.* (2018) Creating A Graft Friendly Environment for Stem Cells in Diseased Brains. J Clin Invest. Vol. 128. No. 1. p116-9. PMID: 29227287
16. Lin, T., Lin, T-C., McGrail, D.J., Bhupal, P.K., Ku, Y-H., Zhang, W., Meng, L., Lin, S-Y., Peng, G., Tsai, R.YL.* (2019) Nucleostemin Reveals A Dichotomous Nature of Genome Maintenance in Mammary Tumor Development. Oncogene. Vol. 38. No. 20. p3919-31. PMID: 30692636
17. Wang, J., McGrail, D.J., Bhupal, P.K., Zhang, W., Lin, K-Y, Ku, Y-H., Lin, T., Wu, H., Tsai, K.C., Li, K., Peng, C-Y, Finegold, M.J., Lin, S-Y., Tsai, R.YL.* (2020) Nucleostemin Modulates Outcomes of Hepatocellular Carcinoma via a Tumor Adaptive Mechanism to Genomic Stress. Mol Cancer Res. 18. No. 5. p723-34. PMID: 32051231
18. Ye, W., Siwko, S., Tsai, R.YL.* (2021) Sex and Race-Related DNA Methylation Changes in Hepatocellular Carcinoma. Int J Mol Sci. 22 (8), 3832. p1-21. PMID: 33917049
19. Crawford, M., Liu, X., Cheng, Y-S.L., Tsai, R.YL.* (2021) Nucleostemin Upregulation and STAT3 Activation as Early Events in Oral Epithelial Dysplasia Progression to Squamous Cell Carcinoma. Neoplasia. Vol. 23 (12). p1289-1299. PMID: 34785448
20. Crawford, M., Johnson, E.H., Liu, K.YP., Poh, C., Tsai, R.YL.* (2022) On the Cutting Edge of Oral Cancer Prevention: Finding Risk-Predictive Markers in Precancerous Lesions by Longitudinal Studies. Cells. Vol. 11 (6), 1033. p1-17. PMID: 35326482
21. Liu, X., Li, Q., Wang, Y., Crawford, M., Bhupal, P.K., Gao, X., Xie, H., Liang, D., Cheng, Y.L., Liu, X., Tsai, R.YL.* (2022) Designing A Novel Mucoadhesive ChemoPatch to Ablate Oral Dysplasia for Cancer Prevention. Small. Vol. 18 (21). 202201561. PMID: 35587597
22. Wang, J., Zhang, W., Liu, X. Kim, M., Zhang, K., and Tsai, R.YL.* (2023) Epigenome-Wide Analysis of Aging Effects on Liver Regeneration. BMC Biol. Vol. 21. No. 1. 30. PMID: 36782243
23. Liu, X., Wang, J., Wu, L.J., Trinh, B., and Tsai, R.YL.* (2024) IMPDH Inhibition Decreases TERT Expression and Synergizes the Cytotoxic Effect of Chemotherapeutic Agents in Glioblastoma Cells. Int J Mol Sci. Vol. 25 (11), 5992. p1-18. doi.org/10.3390/ijms25115992. PMID: 38892179

 Complete List of Publications