Robert W. Lim, Ph.D.
Research Interests
| Cell proliferation and terminal differentiation are often antagonistic processes that have to be tightly regulated in a coordinate manner. Disruptions in the process regulating cell proliferation can interfere with differentiation and result in oncogenesis. Our laboratory is interested in the mechanisms regulating the proliferation and differentiation process using skeletal muscle cells as a model system. Our current research focuses on insulin-like growth factor 1 (IGF-1), a growth factor widely recognized for its major role in muscle development and maintenance in vivo and in vitro, and on Id3, a growth factor-inducible transcriptional and differentiation inhibitor that has been implicated also in oncogenesis, atherosclerosis and tumor-induced angiogenesis. |
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| Specific aspects of our research include: (1) analysis of the signal transduction pathways utilized by IGF-1 to stimulate the replication of undifferentiated muscle cells and those used to promote muscle hypertrophy without inducing DNA synthesis in differentiated muscles; (2) comparison of the effects of IGF-1 on the expression and function of cell cycle regulatory components in proliferating versus differentiated muscle cells. (3) investigation of the transcriptional and post- transcriptional mechanisms regulating the expression and function of Id3 by growth factors and the muscle differentiation process; and (4) characterizing the structural determinants of the Id3 proteins needed to mediate its biological functions. Results from such studies should yield useful information to both developmental and cancer cell biology. In addition, our lab has embarked on collaborative studies to examine mechanisms of histone acetylation and to clone and characterize a novel chloride channel expressed selectively in muscle tissues. |
Professional Background
Dr. Lim obtained his Ph.D. degree in Biochemistry from the University of Washington in 1984. He joined the department in August, 1989, after doing his postdoctoral work at the University of California-Los Angeles.
Selected Publications
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Chen, B. and Lim, R.W. (1997) Physical and functional interactions between the transcriptional inhibitors Id3 and ITF2b: Evidence towards a novel mechanism regulating muscle-specific gene expression. J. Biol. Chem. 272, 2459-2463
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Chen, B.B., Han, B. H., Sun, X.-H. and Lim, R.W. (1997) Inhibition of muscle specific transactivation by HLH462/Id3: Requirement of the C-terminal region of the protein for stable expression and function. Nucleic Acid Research 25, 423-430.
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Montano, M.M. and Lim, R.W. (1997) Glucocorticoid regulation of muscle cell proliferation and differentiation. Endocrine Research 23, 37-57
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Chu, C.Y. and Lim, R. W. (2000) Involvement of p27kip1 and cyclin D3 in the regulation of cdk2 activity during skeletal muscle differentiation. Biochim. Biophy. Acta 1497,175-185.
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Yeh, K.C. and Lim, R.W. (2000) Genomic organization and promoter analysis of the murine Id3 gene. Gene 254, 163-171.
Methodology/Techniques
General molecular biology and recombinant DNA techniques: including cDNA library construction and screening, northern and southern hybridization, PCR, RT-PCR, in vitro site directed mutagenesis, recombinant protein expression, promoter analysis, electrophoretic mobility assay and DNA footprinting.
Biochemical, cell biology and immunological techniques: cell culture, protein phosphorylation, SDSPAGE and immunoblotting, immunoprecipitation, affinity purification, cell fractionation
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