Janis Lem, PhD
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Education
PhD, Microbiology, University of Southern California, Los Angeles, CA, 1987
BS, Biological Sciences, University of Southern California, Los Angeles, CA, 1979
Postdoctoral Training
California Institute of Technology, 1988-93
Postdoctoral research project: Molecular characterization of retina-specific
genes in transgenic mice. Advisor: Melvin I. Simon, Ph.D.
Research Interests
Analysis of rhodopsin gene mutations in retinal degenerations.
Effect of mutations in the rod transducin alpha subunit on photoreceptor cell function.
Research in Dr. Lem's lab focuses on the genetics of inherited retinal degenerations. These blinding diseases afflict approximately 1 in 4,000 individuals in the United States. Work is in progress to identify genetic mutations that cause retinal degenerations and to assess how these mutations alter photoreceptor function. Elucidating the molecular mechanisms by which mutations cause photoreceptor cell degeneration is essential for developing treatment therapies.
Techniques employed:
- molecular biology
- pronuclear transgenesis
- gene knockouts
- cell culture
- histology
- biochemical analysis
Dr. Lem researches the creation of transgenic models of retinal degeneration and other genetically-linked diseases of the eye and visual pathways. She has performed studies of photoreceptor cells and the role of cellular communication in visual function.
Representatives Publications
Mendez A, Krasnoperova NV, Lem J, Chen J: Functional study of rhodospin phosphorylation in vivo. Methods in Enzymology 2000; 316:167
Frederick J, Krasnoperova N, Hoffmann K, Baehr W, Lem J, Ruther K: Retinal degeneration is accelerated when a mutant rhodopsin transgene is expressed on a haploid or null rhodopsin background. Retinal Degenerative Diseases & ExPerimental Therapy (JG Hollyfield, RE Anderson and MM LaVail, eds) Plenum Publishers, New York, NY; 1999
Lem J, Krasnoperova N, Calvert P, Nicolo M, Carmeron D, Losaras B, Makino C, Sidman, R: Morphological, physiological and biochemical changes in rhodopsin knockout mice. Proc. Natl. Acad. Sci USA 1999; 96:736-741
Lem J: Diseases of G-protein-coupled signal transduction pathways: the mamaliam visual system as a model. Seminars in the Neurosciences 1999; 9:232-239
Lem, J. and Makino, C.L. Phototransduction in Transgenic Mice. Current Opinion in Neurobiology 1996; 6:453-458
Raport, C.J., Lem, J., Makino, C., Chen, C.-K., Hobson, A., Baylor, D., Simon, M.I., and Hurley, J.B. (1994) Down-regulation of cGMP Phosphodiesterase Induced by Expression of GTPase-deficient Cone Transducin in Mouse Rod Photoreceptors. Investigative Ophthalmol. Vis. Sci. 35(7):2932-2947.
Chen, J., Tucker, C.L., Woodford, B., Szel, A., Lem, J., Gianella-Borradori, A., Simon, M.I., and Bogenmann, E. (1994) The human blue opsin promoter directs transgene expression in cone and cone bipolar cells in the mouse retina. Proc. Natl. Acad. Sci. USA. 91:2611-2615.
Lem, J., Flannery, J.G., Li, T., Applebury, M.L., Farber, D.B., and Simon, M.I. (1992) Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase b-subunit. Proc. Natl. Acad. Sci. USA. 89: 4422-4426.
Lem, J., Applebury, M.L., Falk, J.D., Flannery, J.G. and Simon, M.I. (1991). Tissue-Specific and Developmental Regulation of Rod Opsin Chimeric Genes in Transgenic Mice. Neuron 6: 201-210.
Lem, J., Chin, A.C., Thayer, M.J., Leach, R.J., and Fournier, R.E.K. (1988). Coordinate regulation of two genes encoding gluconeogenic enzymes by the trans-dominant locus Tse-1. Proc. Natl. Acad. Sci. USA 85: 7302-7306.
Sparkes, R.S., Simon, M., Cohn, V.H., Fournier, R.E.K., Lem, J., Kusak, I., Heinzmann, C., Blatt, C., Lucero, M., Mohandas, T., DeArmond, S.J., Westaway, D., Prusiner, S.B., and Weiner, L.P. (1986). Assignment of the human and mouse prion protein genes to homologous chromosomes. Proc. Natl. Acad. Sci. USA 83: 7358-7362.
Lem, J. and Fournier, R.E.K. (1985). Assignment of the gene encoding cytosolic phosphoenolpyruvate carboxykinase (GTP) to musculus chromosome 2. Som. Cell and Mol. Gen. 11: 633-638.
Calvert, P.D., Govardovskii, V.I., Krasnoperova, N., Anderson, R.E., Lem, J. and Makino, C.L. Membrane protein diffusion sets the speed of rod phototransduction. Nature (2001) 411: 90-94.
Calvert, P.D., Kransoperova, N.V., Lyubarsky, A.L., Isayama, T., Nicolo, M. Kosaras, B., Wong, G., Gannon, K.S., Margolskee, R.F., Sidman, R.L., Pugh, Jr., E.N., Makino, C.L. and Lem, J. Phototransduction in transgenic mice after targeted deletion of the rod transducin -subun it. Proc. Natl. Acad. Sci. USA (2000) 97:13913-13918
Mendez, A., Burns, M.E., Roca, A., Lem, J., Wu, L.-W., Simon, M.I., Baylor, D.A. and Chen, J. Rapid and Reproducible Deactivation of Rhodopsin Requires Multiple Phosphorylation Sites. Neuron (2000) 28:153-164
Book Chapters
Lem, J., Flannery, J., Farber, D., Applebury, M., Raport, C., Hurley, J., Makino, C., Baylor, D. and Simon. M.I. "Transgenic Mouse Models of Retinal Degeneration: Expression of the a-subunit of cGMP Phosphodiesterase and Transducin b-subunits" Retinal Degeneration: Clinical and Laboratory Applications. J.G. Hollyfield, M.M. LaVail, and R. E. Anderson, eds. Plenum Press, New York, 1993, pp 231-242.