Fungal infections; Epigenetic regulation of fungal cell fates; Pathogen-host interaction; Drug resistance
2008-present Professor, Department of Biological Chemistry, UCI
2002-2008 Associate Professor, Department of Biological Chemistry, UCI
1995-2002 Assistant Professor, Department of Biological Chemistry, UCI
1992-1995 Postdoctoral Fellow, Whitehead Institute, MIT
1991 Postdoctoral Fellow, Cornell University
Candida albicans is one of the most frequently isolated fungal pathogens in humans, causing mucosal infections of the oral cavity and reproductive tract in otherwise healthy people, and also causing life-threatening systemic infections in immunocompromised individuals. C. albicans is polymorphic and undergoes reversible morphogenetic transitions between budding yeast, and pseudohyphal and hyphal growth forms. Its ability to switch growth forms is important for the virulence of C. albicans. A major emphasis of our research has been to understand how C. albicans senses host signals and regulates its growth forms and ability to survive and infect at different host sites. Our recent studies focus on identifying yeast and hyphal specific cell surface proteins that modulate the host immune response. Another area of our research is antifungal drug discovery and mechanisms of drug resistance.
Committee of 1000, College of Medicine, UCI, 1998
Burroughs Wellcome New Investigator Award, 1996
Jane Coffin Childs postdoctoral fellowship, 1992
Liu H. Phase separation and cell fate in Candida. Nat Microbiol. 2020 Nov;5(11):1314-1315. PMID:33087900.
Alkafeef SS, Lane S, Yu C, Zhou T, Solis NV, Filler SG, Huang L, Liu H. Proteomic Profiling of the Monothiol Glutaredoxin Grx3 Reveals Its Global Role in the Regulation of Iron Dependent Processes. PLoS Genetics. 2020 June 11;16(6):e100881. PMID: 32525871.
Unoje O, Yang M, Lu Y, Su C, Liu H. Linking Sfl1 Regulation of Hyphal Development to Stress Response Kinases in Candida albicans. mSphere. 2020 Jan 15; 5(1):e00672-19. PMID:31941808.
Lu Y, Su C, Ray S, Yuan Y, Liu H. CO2 signaling through the Ptc2-Ssn3 axis governs sustained hyphal development of Candida albicans by reducing Ume6 phosphorylation and degradation. MBio. 2019 Jan 15;10(1). PMID:30647154
Gao J, Wang H, Li Z, Wong AH, Wang YZ, Guo Y, Lin X, Zeng G, Liu H, Wang Y, Wang J. Candida albicans gains azole resistance by altering sphingolipid composition. Nat Commun. 2019 Jan 15;10(1):317. PMID:30374049
Wang X, Zhu W, Chang P, Wu H, Liu H, Chen J. Merge and separation of NuA4 and SWR1 complexes control cell fate plasticity in Candida albicans. Cell Discov. 2018 Aug 14;4:45. PMID: 30109121
Alkafeef SS, Yu C. Huang L. Liu H. Wor1 establishes opaque cell fate through inhibition of the general co-repressor Tup1 in Candida albicans. PLoS Genetics, 2018 Jan 16;14(1). PMID:29337983
Mood A, Premachandra ID, Hiew S, Wang FQ, Scott K, Oldenhuis N, Liu H, Van Vranken D. Potent Antifungal Synergy of Phthalazinone and Isoquinolones with Azoles Against Candida albicans. ACS Medicinal Chemistry Letters, 2017.
Su C., Lu Y., Liu H., N-acetylglucosamine sensing by a GCN5-related N-acetyltransferase induces transcription via chromatin histone acetylation in fungi. Nature Communications. 7:12916. 2016
Lane S., Di Lena, Tormanen K. Baldi P. Liu H. Function and regulation of Cph2 in Candida albicans. Eukaryot Cell. 2015
Premachandra ID, Scott KA, Shen C, Wang F, Lane S, Liu H, Van Vranken DL. Potent Synergy Between Spirocyclic Pyrrolidinoindolinoses and Fluconazole against Candida albicans. ChemMedChem. 2015 PMID: 26263912
Yan M, Nie X, Wang H, Gao N, Liu H, Chen J. SUMOylation of Wor1 by a novel SUMO E3 ligase controls cell fate in Candida albicans. Mol Microbiol. 2015. PMID: 26112173
Guan Z. & Liu H. The WOR1 5’ untranslated region regulates white-opaque switching in Candida albicans by reducing translational efficiency. Mol. Microbiology. 2015 PMID: 25831958
Guan Z. & Liu H. Overlapping functions between SWR1 deletion and H3K56 acetylation in Candida albicans. Eukaryot Cell, 2015, PMID: 25862154
Lu Y., Su C., Liu H. Candida hyphal Initiation and elongation. Trends Microbiol. 2014 Dec;22(12):707-714. PMID: 25262420
Lu Y., Su C., Unoje O., Liu H. (2014) Quorum sensing controls hyphal initiation in Candida albicans through Ubr1-mediated protein degradation. Proc Natl Acad Sci 111(5):1975-80.
Lu Y., Su C., Solis N.V., Filler S.G. & Liu H. (2013) Synergistic regulation of hyphal elongation by hypoxia, CO2, and nutrient conditions controls pathogenicity of Candida albicans. Cell Host & Microbes 14(5):499-509. PMID: 24237696.
Stevenson JS & Liu H. (2013) Nucleosome assembly factors CAF-1 and HIR modulate epigenetic switching frequencies in an H3K56 acetylation-associated manner in Candida albicans. Eukaryot Cell 12(4):591-603. PMID: 23417560.
Su C., Lu Y., Liu H. (2013) Reduced TOR Signaling Sustains Hyphal Development in Candida albicans by lowering Hog1 basal activity. Mol Biol Cell 24(3):385-97. PMID: 23171549.
Lu Y., Su C. & Liu H. (2012) A GATA Transcription Factor Recruits Hda1 In Response to Reduced Tor1 Signaling To Establish a Hyphal Chromatin State in Candida albicans. PLoS Pathogens 8(4):e1002663. PMID: 22536157.
Stevenson J.S. & Liu H. (2011) Regulation of white and opaque cell type formation in Candida albicans by Rtt109 and Hst3. Mol. Microbiology 81(4):1078-91. PMID: 21749487
Lu Y. Su C. Wang A. & Liu H. (2011) Hyphal development in Candida albicans requires two temporally linked changes in promoter chromatin for initiation and maintenance. PLoS Biology 9(7):e1001105. PMID: 21811397.
Mochon AB., Ye J., Kayala M.A., Wingard J.R., Clancy C.J., Nguyen, M.H., Felgner P., Baldi P., Liu H. (2010) Profiling antibody response with Candida albicans cell surface protein microarray reveals constant host-pathogen interplay and infection-associated antigens during systemic candidiasis. PLoS Pathogens 6(3):e1000827.
Park H., Liu Y., Solis N., Spotkov J., Hamaker J., Blankenship J.R., Yeaman M.R., Mitchell A. P., Liu H., Filler S.G. (2009) Transcriptional Responses of Candida albicans to Epithelial and Endothelial Cells. Eukaryotic Cell 8(10).
Wang A., Raniga P.P., Lane S., Lu Y., Liu H. (2009). Hyphal chain formation in Candida albicans: Cdc28-Hgc1 phosphorylation of Efg1 represses cell separation genes, Mol Cell Biol. 29(16).
Mochon AB, Liu H. (2008) The antimicrobial peptide histatin-5 causes a spatially restricted disruption on the Candida albicans surface, allowing rapid entry of the peptide into the cytoplasm. PloS Pathogens. 4(10):e1000190.
Chou, S., Zhou, S., Song, Y., Liu, H.* and Nie, Q.* (2008). Fus3-triggered Tec1 degradation modulates mating transcriptional output during the pheromone response. Nature Molecular Systems Biology 4:212. (*corresponding author)
Lu, Y., Su, C., Mao, X., Raniga, P.P., Liu, H., *and Chen, J.* (2008). Efg1-mediated recruitment of NuA4 to promoters is required for hypha-specific Swi/Snf binding and activation in Candida albicans. Mol Biol Cell 19(10):4260-72. (*corresponding author)
Wang, A., Lane, S., Tian, Z., Sharon, A., Hazan, I., and Liu, H. (2007). Temporal and spatial control of HGC1 expression results in Hgc1 localization to the apical cells of hyphae in Candida albicans. Eukaryot Cell 6, 253-261.
Huang, G., Wang, H., Chou, S., Nie, X., Chen, J., and Liu, H. (2006). Bistable expression of WOR1, a master regulator of white-opaque switching in Candida albicans. Proc Natl Acad Sci U S A 103, 12813-12818.
Chou, S., Lane, S., and Liu, H. (2006). Regulation of mating and filamentation genes by two distinct Ste12 complexes in Saccharomyces cerevisiae. Mol Cell Biol 26, 4794-4805.
Cao, F., Lane, S., Raniga, P.P., Lu, Y., Zhou, Z., Ramon, K., Chen, J., and Liu, H. (2006). The Flo8 transcription factor is essential for hyphal development and virulence in Candida albicans. Mol Biol Cell 17, 295-307.
Chou, S., Huang, L., and Liu, H. (2004). Fus3-regulated Tec1 degradation through SCFCdc4 determines MAPK signaling specificity during mating in yeast. Cell 119, 981-990.
Hazan, I., and Liu, H. (2002). Hyphal tip-associated localization of Cdc42 is F-actin dependent in Candida albicans. Eukaryot Cell 1, 856-864.
Liu, H. (2002). Co-regulation of pathogenesis with dimorphism and phenotypic switching in Candida albicans, a commensal and a pathogen. Int J Med Microbiol 292, 299-311.
Chen, J., Lane, S., and Liu, H. (2002). A conserved mitogen-activated protein kinase pathway is required for mating in Candida albicans. Mol Microbiol 46, 1335-1344.
Liu, H. (2002). Constructing yeast libraries. Methods Enzymol 350, 72-86.
Hazan, I., Sepulveda-Becerra, M., and Liu, H. (2002). Hyphal elongation is regulated independently of cell cycle in Candida albicans. Mol Biol Cell 13, 134-145.
Liu, H. (2001). Transcriptional control of dimorphism in Candida albicans. Curr Opin Microbiol 4, 728-735.
Lane, S., Zhou, S., Pan, T., Dai, Q., and Liu, H. (2001). The basic helix-loop-helix transcription factor Cph2 regulates hyphal development in Candida albicans partly via TEC1. Mol Cell Biol 21, 6418-6428.
Lane, S., Birse, C., Zhou, S., Matson, R., and Liu, H. (2001). DNA array studies demonstrate convergent regulation of virulence factors by Cph1, Cph2, and Efg1 in Candida albicans. J Biol Chem 276, 48988-48996.
Chen, J., Zhou, S., Wang, Q., Chen, X., Pan, T., and Liu, H. (2000). Crk1, a novel Cdc2-related protein kinase, is required for hyphal development and virulence in Candida albicans. Mol Cell Biol 20, 8696-8708.
Loeb, J.D., Sepulveda-Becerra, M., Hazan, I., and Liu, H. (1999). A G1 cyclin is necessary for maintenance of filamentous growth in Candida albicans. Mol Cell Biol 19, 4019-4027.
Loeb, J.D., Kerentseva, T.A., Pan, T., Sepulveda-Becerra, M., and Liu, H. (1999). Saccharomyces cerevisiae G1 cyclins are differentially involved in invasive and pseudohyphal growth independent of the filamentation mitogen-activated protein kinase pathway. Genetics 153, 1535-1546.
Liu, H., Styles, C.A., and Fink, G.R. (1996). Saccharomyces cerevisiae S288C has a mutation in FLO8, a gene required for filamentous growth. Genetics 144, 967-978.
Liu, H., Kohler, J., and Fink, G.R. (1994). Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science 266, 1723-1726.
Liu, H., Styles, C.A., and Fink, G.R. (1993). Elements of the yeast pheromone response pathway required for filamentous growth of diploids. Science 262, 1741-1744.
Liu, H., Krizek, J., and Bretscher, A. (1992). Construction of a GAL1-regulated yeast cDNA expression library and its application to the identification of genes whose overexpression causes lethality in yeast. Genetics 132, 665-673.
Liu, H., and Bretscher, A. (1992). Characterization of TPM1 disrupted yeast cells indicates an involvement of tropomyosin in directed vesicular transport. J Cell Biol 118, 285-299.
Liu, H., and Bretscher, A. (1989). Disruption of the single tropomyosin gene in yeast results in the disappearance of actin cables from the cytoskeleton. Cell 57, 233-242.
Liu, H., and Bretscher, A. (1989). Purification of tropomyosin from Saccharomyces cerevisiae and identification of related proteins in Schizosaccharomyces and Physarum. Proc Natl Acad Sci U S A 86, 90-93.
R01 GM117111-01A1, 2017-2025
R01 AI099190 (2012-2018)
R01 GM55155 (1997-2015)
Cellular and Molecular Biosciences
Member, Institute for Immunology