The University of Texas Medical School at Houston
Department of Microbiology and Molecular Genetics

Ziyin Li , Ph.D.

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Education:

Ph.D., Institute of Genetics, Chinese Academy of Sciences, 2000

Postdoctoral Fellow, University of California-San Francisco

Research Interests:

Cell cycle regulation in trypanosomes

My laboratory is mainly interested in understanding the molecular mechanism of mitosis and cytokinesis. We use Trypanosoma brucei, a unicellular eukaryote and the causative agent of human sleeping sickness, as a model to address the fundamental questions of how mitosis and cytokinesis are regulated and coordinated during cell division. The advantage of using T. brucei as a model is that this organism is evolutionarily ancient, and thus it provides a unique distant reference point for dissecting crucial biological processes. The current focus is on the cell cycle regulatory pathways consisting of protein kinases such as Aurora B kinase, Polo-like kinase and Tousled-like kinase, spindle-associated motor proteins, and ubiquitin ligases.

We are also interested in the role of ubiquitin-dependent and -independent proteolysis in various cell biological processes. ATP-dependent protease complexes are present in all three kingdoms of life where they ride the cell of mis-folded or damaged proteins and control the level of certain regulatory proteins. These proteases include the 26S proteasome in eukaryotes, Archaea, and Actinomycetales and the HslVU protease in eubacteria. Currently we are investigating the function and regulation of various ubiquitin-dependent pathways and the ubiquitin-independent HslVU-mediated proteolysis pathway in T. brucei. The current focus is on three proteolytic pathways: the Cullin-RING ubiquitin ligase (CRL) and the anaphase-promoting complex/cyclosome (APC/C) on cell cycle control and HslVU protease on mitochondrial DNA replication licensing.

We use a combination of genetics, biochemistry, cell biology, molecular biology, and proteomics to elucidate the molecular and cellular basis of cell division in trypanosomes, which hopefully could provide a few excellent drug targets for chemotherapy.

Selected Publications:

  • Hu L. and Li Z. (2011) A kinetoplastid-specific kinesin is required for cytokinesis and for maintenance of cell morphology in Trypanosoma brucei (submitted)
  • Yu Z. and Li Z. (2011) Structure-function relationship of the Polo-like kinase in Trypanosoma brucei. Journal of Cell Science (In revision)
  • Dang H.Q. and Li Z. (2011) The Cdc45/Mcm2-7/GINS complex in trypanosomes regulates DNA replication and interacts with two Orc1-like proteins in the origin recognition complex. Journal of Biological Chemistry, Epub ahead of print, doi: 10.1074/jbc.M111.240143jbc.M111.240143 [abstract]
  • Li Z., Umeyama T., Li Z., and Wang C.C. (2010) Polo-like kinase guides cytokinesis in Trypanosoma brucei through an indirect means. Eukaryotic Cell 9: 705-716 [abstract]
  • Li Z., Umeyama T., and Wang C.C. (2009) The Aurora kinase in Trypanosoma brucei plays distinctive roles in metaphase-anaphase transition and cytokinetic initiation. PLoS Pathogens 5(9):1000575 [abstract]
  • Li Z., Umeyama T., and Wang C.C. (2008) The chromosomal passenger complex and a mitotic kinesin interact with the Tousled-like kinase in trypanosomes to regulate mitosis and cytokinesis. PLoS ONE, 3(11): e3814 [abstract]
  • Li Z., and Wang C.C. (2008) KMP-11, a basal body and flagellar protein, is required for cell division in Trypanosoma brucei. Eukaryot. Cell, 7: 1941-1950 [abstract]
  • Li Z., Lee J.H., Chu F., Burlingame A.L., Günzl A., and Wang C.C. (2008) Identification of a novel chromosomal passenger complex and its unique localization during cytokinesis in Trypanosoma brucei. PLoS ONE, 3(6): e2354 [abstract]
  • Li Z., Lindsay M.E., Motyka S.A., Englund P.T., and Wang C.C. (2008) Identification of a bacterial-like HslVU protease in the mitochondria of Trypanosoma brucei and its role in mitochondrial DNA replication. PLoS Pathog., 4(4): e1000048 [abstract]
  • Li Z., Gourguechon S., and Wang C.C. (2007) Tousled-like kinase in a microbial eukaryote regulates spindle assembly and S-phase progression by interacting with Aurora kinase and chromatin assembly factors. J. Cell Sci., 120: 3883-3894 [abstract]
  • Li Z.*, Tu X.*, and Wang C.C. (2006) Okadaic acid overcomes the blocked cell cycle caused by depleting cdc2-related kinases in Trypanosoma brucei. Exp. Cell Res., 312: 3504-3516 (* equal contribution) [abstract]
  • Li Z., and Wang C.C. (2006) Changing roles of Aurora-B kinase in two life cycle stages of Trypanosoma brucei. Eukaryot. Cell, 5: 1026-1035 [abstract]
  • Tu X., Kumar P., Li Z., and Wang C.C. (2006) An Aurora kinase homologue is involved in regulating both mitosis and cytokinesis in Trypanosoma brucei. J. Biol. Chem., 281: 9677-9687 [abstract]
  • Li Y., Li Z., and Wang C.C. (2003) Differentiation of Trypanosoma brucei may be stage non-specific and does not require progression of cell cycle. Mol. Microbiol., 49: 251-265 [abstract]
  • Li Z., and Wang C.C. (2003) A PHO80-like cyclin and a B-type cyclin control the cell cycle of the procyclic form of Trypanosoma brucei. J. Biol. Chem., 278: 20652-20658 [abstract]
  • Li Z., and Wang C.C. (2002) Functional characterization of the 11 non-ATPase subunit proteins in the trypanosome 19S proteasomal regulatory complex. J. Biol. Chem., 277: 42686-42693 [abstract]
  • Li Z., Zou C.-B., Yao Y., Hoyt M.A., McDonough S., Mackey Z.B., Coffino P., and Wang C.C. (2002) An easily dissociated 26S proteasome catalyzes an essential ubiquitin-mediated protein degradation pathway in Trypanosoma brucei. J. Biol. Chem., 277: 15486-15498 [abstract]
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