Robert Yu-Lin Tsai

Robert Yu-Lin Tsai

Associate Professor

Center for Translational Cancer Research
2121 W. Holcombe Blvd.
Houston, TX   77030-3303

Phone: 713-677-7690

Education and Training

Dr. Tsai received his undergraduate and MD degrees at National Taiwan University and an internship and residency in Neurology at the National Taiwan University Hospital.  He received a Ph.D. in Neurosciences at Johns Hopkins University School of Medicine in 1996 and was a Research Fellow at the National Institute of Neurological Disorders and Stroke, National Institutes of Health (1997-2003).  In 2003 he was appointed an Assistant Professor in the Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, The Texas A&M Health Science Center in the Texas Medical Center, Houston, Texas and promoted to tenured Associate Professor in 2008.  He holds a joint appointment in the Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center.

Research Interests

The research interest of my laboratory is focused on the molecular mechanism that drives the self-renewing proliferation of stem cells, with the hope that we can use this knowledge to enhance the endogenous regenerative process to repair damaged tissues caused by diseases or injuries, particularly in the central nervous system, and, on the flip side, to reduce the uncontrolled proliferation seen in metastatic and high-grade tumors. The biological systems we use are ES, primary neural stem cell culture, and cancer cell lines, as well as mouse genetic models. The molecular target of our present studies is a family of nucleolar GTPases, one of which, nucleostemin (NS), confers a unique nucleolar state in the stem cells. NS was previously identified as enriched in the stem cell population, and shown to play important roles in keeping the neural stem cells and cancer cells in the cell cycle. The activity of NS is regulated by a small molecule in the cells (GTP) that serves as a molecular switch controlling the on and off states. Our work suggests a model in which continuously dividing cells use NS as a sensor to control their rate of division in response to changes that take place in their microenvironment. The mechanism by which NS and NS-related genes control tissue homeostasis in adult animals is being addressed in the following directions: 1) defining the unique nucleolar state in stem cells; 2) determining the signaling pathway that regulates the expression and activity of nucleostemin (NS) in stem cells and during adult tissue regeneration; and 3) establishing the role of NS-expressing cells in the tumorigenic process, with an emphasis on the brain, breast, and prostate tumors.

Five Most Significant Publications Prior to 2011

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

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

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

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

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

Publications 2011

Meng L, Hsu JK, Tsai, RYL (2011) GNL3L Depletion Destabilizes MDM2 and Induces p53-Dependent G2/M Arrest. Oncogene 30(14): 1716-1726.
Tsai, Y.L. (2011) Chapter 13: New Frontiers in The Nucleolar Research: Nucleostemin and Related Proteins. The Nucleolus (Protein Reviews 15).  Edited by Mark O. Olson and M. Zouhair Atassi.  Springer pg 301-320.
Meng L, Hsu JK, Zhu Q, Lin T,Tsai RYL. (2011) Nucleostemin Inhibits TRF1 Dimerization and Shortens Its Dynamic Association with The Telomere.  J Cell Sci 124(21): 3706-3714.
Lin T, Meng L, Tsai RYL. (2011) GTP Depletion Synergizes the Anti-Proliferative Activity of Chemotherapeutic Agents in a Cell Type-Dependent Manner. Biochem Bioph Res Commun 414(2): 403-408. 

Publications 2012

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. 197:613-624.
Peng, G., Dai, H., Zhang, W., Hsieh, H-J., Pan, M-R., Park, Y-Y., Tsai, R.YL. Bedrosian, I., Lee, J-S., Ira, G, and Lin, S-Y. (2012) Human Nuclease/Helicase DNA2 Alleviates Replication Stress by Promoting DNA End Resection. Cancer Res. 72:2802-2813.

Publications 2013

Yang C, Lu W, Lin T, You P, Ye M, Huang Y, Jiang X, Wang C, Wang F, Lee MH, Yeung SC, Johnson RL, Wei C, Tsai RY, Frazier ML, McKeehan WL, Luo Y. (2013) Activation of liver FGF21 in hepatocarcinogenesis and during hepatic stress.  BMC Gastroenterol.13(1):67. [Epub 17 Apr 2013] PMID: 23590285
Meng L, Lin T, Peng G, Hsu JK, Lee S, Lin SY, Tsai RY. Nucleostemin deletion reveals an essential mechanism that maintains the genomic stability of stem and progenitor cells.  (2013) Proc Natl Acad Sci U S A. [Epub 2013 Jun 24] PMID: 23798389

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.

Publications 2014

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.

Tsai, R.YL.* and Pederson, T.* (2014) Connecting The Nucleolus to The Cell Cycle and Human Disease. FASEB J. Vol. 28. No. 8. p. 3290-3296.

Tsai, R.YL.* (2014) Turning A New Page on Nucleostemin and Self-renewal. J Cell Sci. Vol. 127. No. 18. p3885-3891