Dr Hung-Ji Tsai

School of Biosciences
Assistant Professor

Contact details

Email: h.tsai@bham.ac.uk
Twitter: @HJTsai

Address: N106, Institute of Microbiology and Infection
School of Biosciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT

Dr Hung-Ji Tsai is interested in how aneuploidy, an unbalanced genomic state with gain or loss of chromosomes, enables rapid adaptation to diverse environment. His research focus is to understand the distinct cellular processes driven by aneuploidy (and other large-scale genome instability) during the acquisition of antifungal drug resistance.

Qualifications

PhD, University of Minnesota, Minneapolis, MN, USA, 2013
MSc, National Taiwan University College of Medicine, Taipei, Taiwan, 2004
BSc, National Taiwan University, Taipei, Taiwan, 2002

Biography

Hung-Ji completed his BSc in Agricultural Chemistry at the National Taiwan University in Taiwan in 2002 and later moved to United States for his PhD training at the University of Minnesota in 2007. During his thesis studies, he identified genomic features of replication origins in human fungal pathogen Candida albicans, using both experimental and computational approaches. In 2013, he started his postdoctoral research, studying the physiological impacts of aneuploidy in both yeast and mammalian cell cultures at the Stowers Institute and the Johns Hopkins University. He found that aneuploidy leads to a general hypo-osmotic stress due to proteome imbalance, that alters the regulation of cell surface dynamics and intracellular homeostasis. In 2016, he received Young Investigator Award from Prostate Cancer Foundation from his proposal, Targeting Karyotype Heterogeneity in Prostate Cancer. In 2019, he joined Immunology Division of the Pathology Department at the Johns Hopkins School of Medicine to develop molecular technologies for antigen discovery. In January 2020, Hung-Ji moved to the United Kingdom and started his own research group at the University of Birmingham.

Postgraduate supervision

Students interested in working with Hung-Ji should contact him directly at h.tsai@bham.ac.uk

Research

Our research group is broadly interested in how cells survive stress conditions. A major focus is to investigate the molecular mechanisms in response to stress in cells with ongoing large-scale genome instability, mainly in aneuploid cells. While aneuploidy is frequently observed in eukaryotic genome and generates genetic diversity, the physiological impact of aneuploidy contributing to cellular adaptation under stress remains poorly known. We aim to study:

How do aneuploid cells respond to stress?
How do aneuploid fungi interact with the host during the evolution of drugs

Our group employs molecular tools, experimental evolution, genomics and cell biological techniques to address fundamental questions in fungal species, including Saccharomyces cerevisiaeand Candida albicans

Publications

Tsai H-J, Nelliat AR. 2019. A Double-Edged Sword: Aneuploidy is a Prevalent Strategy in Fungal Adaptation. Gene 10: 787. https://doi.org/10.3390/genes10100787

Tsai H-J, Nelliat AR, Choudhury MI, Kucharavy A, Bradford WD, Cook ME, Kim J, Mair DB, Sun SX, Schatz MC, Li R. 2019. Hypo-osmotic-like stress underlies general cellular defects of aneuploidy. Nature 570:117–121. https://doi.org/10.1038/s41586-019-1187-2

Bijlani S, Thevandavakkam MA, Tsai H-J, Berman J. 2019. Autonomously Replicating Linear Plasmids That Facilitate the Analysis of Replication Origin Function in Candida albicans. mSphere 4:e00103-19. https://doi.org/10.1128/mSphere.00103-19

Zhu J, Tsai H-J, Gordon MR, Li R. 2018. Cellular Stress Associated with Aneuploidy. Dev Cell 44:420–431. DOI: 10.1016/j.devcel.2018.02.002

Mulla WA, Seidel CW, Zhu J, Tsai H-J, Smith SE, Singh P, Bradford WD, McCroskey S, Nelliat AR, Conkright J, Peak A, Malanowski KE, Perera AG, Li R. 2017. Aneuploidy as a cause of impaired chromatin silencing and mating-type specification in budding yeast. elife 6:e27991 DOI: 10.7554/eLife.27991

Chen G, Mulla WA, Kucharavy A, Tsai H-J, Rubinstein B, Conkright J, McCroskey S, Bradford WD, Weems L, Haug JS, Seidel CW, Berman J, Li R. 2015. Targeting the adaptability of heterogeneous aneuploids. Cell 160:771–784. DOI: 10.1016/j.cell.2015.01.026

Tsai H-J, Baller JA, Liachko I, Koren A, Burrack LS, Hickman MA, Thevandavakkam MA, Rusche LN, Berman J. 2014. Origin replication complex binding, nucleosome depletion patterns, and a primary sequence motif can predict origins of replication in a genome with epigenetic centromeres. MBio 5:e01703–14. DOI: https://doi.org/10.1128/mBio.01703-14

Furniss KL, Tsai H-J, Byl JAW, Lane AB, Vas AC, Hsu W-S, Osheroff N, Clarke DJ. 2013. Direct monitoring of the strand passage reaction of DNA topoisomerase II triggers checkpoint activation. PLoS Genet 9:e1003832.

Hsu W-S, Erickson SL, Tsai H-J, Andrews CA, Vas AC, Clarke DJ. 2011. S-phase cyclin-dependent kinases promote sister chromatid cohesion in budding yeast. Mol Cell Biol 31:2470–2483.

Koren A, Tsai H-J, Tirosh I, Burrack LS, Barkai N, Berman J. 2010. Epigenetically-inherited centromere and neocentromere DNA replicates earliest in S-phase. PLoS Genet 6:e1001068.

Beauchene NA, Díaz-Martínez LA, Furniss K, Hsu W-S, Tsai H-J, Chamberlain C, Esponda P, Giménez-Abián JF, Clarke DJ. 2010. Rad21 is required for centrosome integrity in human cells independently of its role in chromosome cohesion. Cell Cycle 9:1774–1780.

Giménez-Abián JF, Díaz-Martínez LA, Beauchene NA, Hsu W-S, Tsai H-J, Clarke DJ. 2010. Determinants of Rad21 localization at the centrosome in human cells. Cell Cycle 9:1759–1763.

Huang Y-C, Tseng S-F, Tsai H-J, Lenzmeier BA, Teng S-C. 2010. Direct interaction between Utp8p and Utp9p contributes to rRNA processing in budding yeast. Biochem Biophys Res Commun 393:297–302.

Tseng S-F, Shen Z-J, Tsai H-J, Lin Y-H, Teng S-C. 2009. Rapid Cdc13 turnover and telomere length homeostasis are controlled by Cdk1-mediated phosphorylation of Cdc13. Nucleic Acids Res 37:3602–3611.

Tsai H-J, Huang W-H, Li T-K, Tsai Y-L, Wu K-J, Tseng S-F, Teng S-C. 2006. Involvement of topoisomerase III in telomere-telomere recombination. J Biol Chem 281:13717–13723.

Wen W-Y, Tsai H-J, Lin C-C, Tseng S-F, Wong C-W, Teng S-C. 2006. Telomere configuration influences the choice of telomere maintenance pathways. Biochem Biophys Res Commun 343:459–466.

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