Li-Yuan Yu-Lee, Ph.D. - Faculty
Professor, Departments of Medicine, Molecular & Cellular Biology, Pathology & Immunology, and Program in Cell and Molecular Biology
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.
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.
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.
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: (Students from my lab* and other labs^)
*Stevens AM, Wang Y-f, Sieger KA, *Lu H-f, and Yu-Lee L-y (1995) Biphasic transcriptional regulation of the interferon-regulatory factor-1 gene by prolactin: Involvement of Gamma-interferon-activated sequence and Stat-related proteins. Mol. Endocrinol. 9:513-525.
Wang Y-f, *O'Neal KD and Yu-Lee L-y (1997) Multiple prolactin receptor cytoplasmic residues and Stat1 mediate prolactin signaling to the IRF-1 promoter. Mol. Endocrinol. 11:1353-1364.
*Luo G and Yu-Lee L-y (2000) Stat5 inhibits NFkB-mediated signaling. Mol. Endocrinol. 14:114-123.
- Yu-Lee L-y (2002) Prolactin modulation of immune and inflammatory responses. Rec. Prog. Hormone Res. 57:435-455.
Kim J, Luo W, Chen D-T, Earley K, Tunstead JR, Yu-Lee L-y and Lin S-H (2003) Antitumor activity of the 16-kDa prolactin fragment in prostate cancer. Cancer Res. 63:386-393.
- *Lee S-H, Mazumdar T, ^Galfione M, Garcia GE, Feng L, Kim J, Eissa NT, Lin S-H and Yu-Lee L-y. 16-kDa prolactin downregulates iNOS expression in endothelial cells through the inhibition of IRF-1. Submitted.
*Morris SM, Albrecht U, Reiner O, Eichele G and Yu-Lee L-y (1998) The lissencephaly gene product LIS1, a protein involved in neuronal migration, interacts with a nuclear movement protein NUDC. Curr. Biol. 8:603-606.
*Aumais JP, ^Williams SN, Luo W, *Nishino M, Caldwell KA, Caldwell GA, Lin S-H and Yu-Lee L-y (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 and Erikson RL (2003) A role for Plk1 phosphorylation of NudC in cytokinesis. Dev. Cell 5:127-138.
Lin S-H, *Nishino M, Luo W, *Aumais JP, ^Galfione M, Kuang J and Yu-Lee L-y (2004) Inhibition of prostate tumor growth by overexpression of NudC, a microtubule motor-associated protein. Oncogene 23:2499-2506.For a complete list of Dr. Yu-Lee's publications, visit PubMed.
Contact Information: Li-yuan Yu-Lee, Ph.D.
Department of Medicine
Baylor College of Medicine
One Baylor Plaza, 535E
Houston, Texas 77030, U.S.A. Phone: 713-798-4770