Li-Yuan Yu-Lee, Ph.D.
Professor Departments of Medicine, Molecular and Cellular Biology and Immunology
Ph.D., Columbia University
Postdoctoral, Baylor College of Medicine
Research Interests:
Signal Transduction Pathways to Immune and Inflammatory Responses
Our laboratory is interested in understanding signal transduction mechanisms in immune, inflammatory responses and in cancer progression. Three areas of research are in progress: 1) Prolactin signaling and action during immune and inflammatory responses; 2) 16-kDa prolactin (a fragment of 23-kDa prolactin) inhibition of angiogenesis and tumorigenesis; and 3) NudC (a cytokine-regulated gene) regulation of cellular transport and cell division pathways.
1) PRL signaling-PRL regulates the growth, differentiation, maturation and apoptosis of many target cells and tissues. Elevated PRL levels may contribute to the prevalence of women in autoimmune diseases. PRL stimulates the transcription of a master cytokine response gene, interferon regulatory factor-1 (IRF-1). PRL-inducible Stat1 positively while PRL-inducible Stat5 negatively regulates IRF-1 transcription via competition for coactivators. Stat5 also inhibits NFkB signaling, suggesting negative cross talk between different cytokine signaling pathways. The molecular determinants of Stat5 inhibition of NFkB signaling to a proinflammatory cytokine gene are under analysis both in vitro and in vivo.
2) 16-kDa PRL signaling-16-kDa PRL (16k PRL), a natural proteolytic fragment of PRL, has strong antiangiogenic and antitumor activities. One way in which 16k PRL attenuates tumor angiogenesis is by inhibiting the transcription of IRF-1 and IL-1b-inducible NO synthase (iNOS), thus attenuating the production of NO, an endothelial cell survival factor. The molecular targets of 16k PRL inhibition at the level of Sp1, Stat1 and NFkB signaling to the IRF-1 gene are under analysis. Further, DNA microarray identified IGFBP5 and Dickkopf-1 (Dkk-1), two secreted factors, as novel mediators of 16k PRL action in endothelial cells. How these factors mediate 16k PRL induction of apoptosis in retinal capillary networks and endothelial cells are under analysis.
3) NudC regulation of cell signaling and cell division-NudC, a highly conserved protein from fungus to man, is a novel microtubule dynein motor-associated protein. NudC may be involved in the reorientation of the cytoskeleton and vesicular networks towards the site of contact when T cells contact antigen-presenting cells. NudC is also localized to key mitotic structures during cell division. NudC interacts with different factors to regulate these diverse cellular processes. First, NudC interacts with Lis-1, the lissencephaly gene product, and may be involved in neurogenesis and neuronal migration. Second, NudC interacts with Plk1, the mitotic polo-like kinase 1, and regulates the temporal and spatial localization of Plk1 during cell division. In turn, Plk1 phosphorylation of NudC is critical for the completion of cytokinesis. Aberrant NudC expression results in mitosis and cytokinesis defects and induces multinucleation and aneuploidy, a hallmark of cancer progression. Third, NudC interacts with components of the dynein/dynactin motor. NudC may regulate dynein functions during cell signaling, vesicular transport, cell migration and cell division. Understanding NudC functions may provide new insights into diverse cellular processes including intracellular transport during T cell activation, viral infection and neurodegenerative diseases, and cancer progression.
Selected Publications:
Ishii S, Kurasawa Y, Wong J, Yu-Lee LY. Histone deacetylase 3 localizes to the mitotic spindle and is required for kinetochore-microtubule attachment. Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4179-84. Epub 2008 Mar 6. PubMed PMID: 18326024; PubMed Central PMCID: PMC2393771.
Lee SH, Kunz J, Lin SH, Yu-Lee LY. 16-kDa prolactin inhibits endothelial cell migration by down-regulating the Ras-Tiam1-Rac1-Pak1 signaling pathway. Cancer Res. 2007 Nov 15;67(22):11045-53. PubMed PMID: 18006851.
Nishino M, Kurasawa Y, Evans R, Lin SH, Brinkley BR, Yu-Lee LY. NudC is required for Plk1 targeting to the kinetochore and chromosome congression. Curr Biol. 2006 Jul 25;16(14):1414-21. PubMed PMID: 16860740.
Lee SH, Nishino M, Mazumdar T, Garcia GE, Galfione M, Lee FL, Lee CL, Liang A, Kim J, Feng L, Eissa NT, Lin SH, Yu-Lee LY. 16-kDa prolactin down-regulates inducible nitric oxide synthase expression through inhibition of the signal transducer and activator of transcription 1/IFN regulatory factor-1 pathway. Cancer Res. 2005 Sep 1;65(17):7984-92. PubMed PMID: 16140971.
Lin S-H, et al. (2004) Inhibition of prostate tumor growth by overexpression of NudC, a microtubule motor-associated protein. Oncogene 23:2499-2506.
Aumais JP, et al. (2003) A role for NudC, a dynein-associated nuclear movement protein, in mitosis and cytokinesis. J. Cell Sci. 116:1991-2003.
Zhou T-H, Aumais JP, Liu X, Yu-Lee L-y, Erikson RL. (2003) A role for Plk1 phosphorylation of NudC in cytokinesis. Dev. Cell 5:127-138.
Yu-Lee L-y. (2002) Prolactin modulation of immune and inflammatory responses. Rec. Prog. Hormone Res. 57:435-455.
Aumais JP, et al. (2001) NudC associates with Lis1 and the dynein motor at the leading pole of neurons. J. Neurosci. 21:RC187.
Luo G, Yu-Lee L-y. (2000) Stat5 inhibits NF?B-mediated signaling. Mol. Endocrinol. 14:114-123.
Morris SM, Albrecht U, Reiner O, Eichele G, Yu-Lee L-y. (1998) he lissencephaly gene product LIS1, a protein involved in neuronal migration, interacts with a nuclear movement protein NUDC. Curr. Biol. 8:603-606.
For more publications, see listing on PubMed.
Contact Information:
Li-yuan Yu-Lee, Ph.D.
713-798-4770
Fax: 713-798-2050
E-mail: yulee@bcm.edu
Updated: 11/09