Leyuan Liu

Biography

Leyuan Liu received a Bachelor of Science at Jiangxi Agricultural University, Jiangxi, Master of Science at the Graduate School of Chinese Academy of Agricultural Sciences, Beijing, China and Ph.D. in Genetics in 1997 at Texas A&M University, College Station, Texas. He was a Postdoctoral Research Associate (1998-1999) in the Department of Biochemistry and Biophysics, Texas A&M University, College Station, Postdoctoral Research Associate (1999-2002), Assistant Research Scientist (2002-2004) and Associate Research Scientist (2004-2006) in the Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas. He was promoted to Assistant Professor (Research Track) in 2006.

Research

My primary interest is to decipher the molecular mechanism of tumor suppression using C19ORF5-mediated RASSF1A tumor suppression as a model. RASSF1A acts as a microtubule stabilizing factor and regulates the mitotic spindle assembly. Similar to microtubular stabilizer and one of the most effective cancer chemotherapy drugs paclitaxel, its overexpression causes microtubule hyperstabilization, mitosis disruption, and specific interaction with C19ORF5. C19ORF5 is a hyperstabilized microtubule-specific binding protein whose accumulation causes mitochondrial aggregation and genome destruction (MAGD) and eventually cell death.

Based on our previous studies, we hypothesize that when mitotic checkpoints are hopelessly stalled by failure of the mitotic apparatus and normal chromosome alignment and segregation, the spindle microtubules become hyperstabilized so both RASSF1A and C19ORF5 will accumulate. This causes prolonged association of mitochondria with the mitotic spindle, then aggregation and then mitotic cell death. By this mechanism, cells that could give rise to a defective genome upon completion of a mitosis. This prevents inheritance and clonal amplification of aneuploidy which is being given increasing attention as an underlying factor in the continuous evolution of genetic flexibility in tumors. Accordingly, our research is focusing on the roles of RASSF1A and C19ORF5 on mitotic spindle assembly, the dynamics of mitochondrial distribution along the mitotic spindle and the mechanism underlying MAGD.

Several interactive proteins with RASSF1A and C19ORF5 are potentially involved in inherited human neural diseases. For example, in addition to RASSF1A and C19ORF5, prefoldin homologue UXT interacts with mitochondria-associated proteins LRPPRC and DSCR1. A mutation in LRPPRC underlies Leigh syndrome, French-Canadian type (LSFC), while overexpression of DSCR1 is associated with Downs syndrome. The common consequence of the two syndromes is the early onset of Alzheimer’s disease. We believe that the UXT-LRPPRC complex facilitates the assembly of mitochondria on microtubular tracks with the assistance of microtubule associated proteins RASSF1A and C19ORF5. Misfolding and aggregation of one or more proteins in the complex cause perinuclear clustering of mitochondrial aggregates and deficiency of mitochondria in the synapse of neuron cells. This leads to neurodegeneration. Our research includes the roles of microtubule dynamics and MAGD activity in neurodegenerative diseases as Alzheimer’s. Currently we are combining the biochemical, genetic and cell biology approaches to test our hypotheses prior to development of animal models for use in strategies of prevention or cure of the diseases.

Five Most Significant Publications Prior to 2005

Liu L., M.E. Wales and J.R. Wild (1997) Conversion of the Allosteric Regulatory Patterns of the Aspartate Transcarbamoylases by Exchange of a Single Beta-strand between the Diverged Regulatory Chains. Biochemistry 36: 3126-3132.

Liu L., M.E. Wales and J.R. Wild (1998) Temperatural Influence on the Allosteric Regulation of the Native and Chimeric Aspartate Transcarbamoylases. J. Mol. Biol. 282: 891-901.

Liu L, M.E. Wales and J.R. Wild (2000) Allosteric Signal Transmission Involves Synergy between Discrete Structural Units of the Regulatory Subunit of Aspartate Transcarbamoylases. Arch. Biochem. Biophys. 373: 352-360.

Liu L. and W.L. McKeehan (2002) Sequence Analysis of LRPPRC and Its SEC1 Domain Interaction Partners Suggests Roles in Cytoskeletal-associated Vesicular Trafficking, Nucleocytosolic Shuttling and Chromosome Activity. Genomics 79: 124-136.

Liu L., A. Vo, G. Liu and W.L. McKeehan (2002) Novel Complex Integrating Mitochondria and the Microtubular Cytoskeleton with Chromosome Remodeling and Tumor Suppressor RASSF1 Deduced by in Silico Homology Analysis, Interaction Cloning in Yeast and Colocalization in Cultured Cells. In Vitro Cell. Dev. Biol. Anim. 38: 582-594.

Publications 2005

Liu, L., A. Vo, and W.L. McKeehan (2005) Specificity of the methylation-suppressed A isoform of candidate tumor suppressor RASSF1 for microtubule hyperstabilization is determined by cell death inducer C19ORF5. Cancer Res. 65: 1830-1838.

Liu, L., A. Vo, G. Liu, and W.L. McKeehan (2005) Distinct structural domains within C19ORF5 support association with stabilized microtubules and mitochondrial aggregation and genome destruction (MAGD). Cancer Res. 65: 4191-4201.

Liu, L., A. Vo, G. Liu, and W.L. McKeehan (2005) Putative tumor suppressor RASSF1 interactive protein and cell death inducer C19ORF5 is a DNA binding protein. Biochem. Biophys. Res. Commun. 332:670-676.

Publications 2007

Moss, T.N., A. Vo, W.L. McKeehan and L. Liu (2007) UXT (Ubiquitously Expressed Transcript) causes mitochondrial aggregation. In Vitro Cell. Devel. Biol. Animal 43: 139-146 [Epub 2007 Mar 21].

Eriksson, M., Samuelsson, H., Samuelsson E-B., Liu, L, McKeehan, W.L., Benedikz, E., Sundstrom, E.  (2007) The NMDAR subunit NR3A interacts with microtubule-associated protein 1S in the brain.  Biochem. Biophys. Res. Commun. 361: 127-132 [Epub 2007 Jul 16].

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