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Robert Tsai

Robert YL Tsai
Robert YL Tsai, MD, PhD

Professor

Center for Translational Cancer Research

Contact

Translational Medical Sciences
IBT Center For Translational Cancer Research; 1201 TAMUS
Texas A&M Health Science Center
Houston, TX 77030
robtsari@tamu.edu
Phone: 713.677.7690

Education and Training

  • National Taiwan University, MD, 1981 - 1988
  • National Taiwan University Hospital, Neurology Residency, 1988 - 1991
  • Johns Hopkins University School of Medicine, PhD, 1991 - 1996
  • Johns Hopkins University School of Medicine, Howard Hughes Associate, 1996 - 1997
  • NIH/NINDS, Research Associate, 1997 - 2003

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.

Awards, Recognition and Service

  • Genome-Wide DNA Methylation Markers for Predicting the Risk of Liver Cancer in Non-Alcoholic Fatty Livers awarded by Cancer Prevention and Research Institute of Texas (Austin, Texas)
  • Nucleostemin: A New Tumor Addictive Mechanism, Outcome Predictor, and Therapeutic Target for Hepatocellular Carcinoma awarded by Cancer Prevention and Research Institute of Texas (Austin, Texas)
  • Aging Effect on Genome Maintenance during Hepatocyte Regeneration awarded by DHHS-NIH-National Institute on Aging
  • Role of Nucleostemin in Conferring The Drug Resistance of Hepatocellular Carcinoma awarded by DHHS-NIH-National Cancer Institute

Representative 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
  24. Liu, X., Wang, J., Li, F., Timchenko, N., and Tsai, R.YL.* (2024) Transcriptional Control of A Stem Cell Factor Nucleostemin in Liver Regeneration and Aging. PLoS One. 19(9), e0310219 (doi:10.1371/journal.pone.0310219). (PMID: 39259742)
  25. Liu, X. and Tsai, R.YL.* (2024) Efficient Gene Knockdown in the Liver via Intrasplenic Injection of AAV8-Delivered Small Hairpin RNA. J Vis Exp. (213), e67376. (doi:10.3791/67376). PMID: 39555801
  26. Li, J., Liu, X., Tran, T.T., Lee, M., Tsai, R.YL.* (2025) DNA Methylation Changes and Target Gene Expression in Fatty Liver Progression from Simple Steatosis to Advanced Fibrosis. Liver Int. Vol. 45 (3), e70040. (doi.org/10.1111/liv.70040). PMID: 39982030
  27. Kim, D.M., Pan, Q., Liu, Z., Ai, W., Han, H.W., Banu, S., Tsai, R.YL., Wright, G.A., Guo, S.*, Sun, Y.* (2025) GHSR-Foxo1 Signaling in Macrophages Promotes Liver Fibrosis via Inflammatory Response and Hepatic Stellate Cell Activation. Adv Sci (Weinh). Vol. 12 (33), e04223.(doi:10.1002/advs.202504223). PMID: 40479577
  28. Mishra, P., Ma, J., Xie, H., Li, F., Tsai, R.Y.L., Liang, D.* (2026) Simultaneous Quantification of Cytidine, Methylcytidine, and Hydroxymethylcytidine by Isotope-Dilution LC-MS/MS with Application to Mouse Liver Samples. J Chromatogr A. 1769:466721 (doi: 10.1016/j.chroma.2026.466721). PMID: 41581428

 Complete List of Publications

Lab Members

CURRENT LAB MEMBERS

Research Associate

  • Fang Li, Ph.D. (fangli@tamu.edu)
  • Xiaoqin Liu, M.B., Ph.D. (xiaoqin.liu@tamu.edu)

 Research Assistant

  • Tran T. Tran, B.S. (tran.tran@tamu.edu)

FORMER LAB MEMBERS

  • Tao Lin, PhD Student
  • Joseph Hsu, PhD Student
  • Lingjun Meng, PhD Student
  • Wessam Ibrahim, PhD Student
  • Qubo Zhu, PhD Student

  • Wenrui Ye, PhD, Senior Research Associate
  • Junying Wang, MB, PhD, Senior Research Associate

  • Yue Chen, PhD, Postdoctoral Fellow
  • Tsung-Chin Lin, Postdoctoral Fellow
  • Hiroaki Yasumoto, MD, PhD, Postdoctoral Fellow

  • Anna-Maria Baptiste B.S., M.S.
  • Dennis Chan, B.S.
  •  Xuxia Tian, Ph.D. Research Assistant
  • Madeleine Crawford, BS, Research Assistant
  • Ruijun Shen, BS, Research Assistant
  • Parnit Bhupal, DDS/MS, Research Assistant
  • Yi-Tsang Lee, BS, MS, Research Assistant
  • Kay Pham, BS, Research Assistant

  • Wen Zhang, MD, Visiting Scientist
  • Hongfu Wu, MD, PhD, Visiting Scientist
  • Guanqun Huang, MD, Visiting Scientist
  • Yuning Bai, MD, PhD, Visiting Scientist
  • Laura Wu, MD, PhD, Visiting Scientist
  • Sun Lee, MD, PhD, Visiting Scientist
  • Jun Teishima, MD, PhD, Visiting Scientist

  • Ivan Perez, 2025 IBT Summer Research Program Student
  • Gabriela Jammar, 2024 IBT Summer Research Program Student
  • Pallavi Pradeep, 2024 IBT Summer Intern
  • Britni Trinh, 2023 IBT Summer Research Program Student
  • Eliza Hazel Johnson, 2021 Hamill Summer Research Program Student