Leslie Thompson
Ph.D., University of California, Irvine, 1988
University of California, Irvine
Department of Biological Chemistry
Irvine, CA 92697
Office: (949) 824-6756, 1910
lmthomps@uci.edu
Research Interests:
Molecular biology of Hydra development
Research in the Thompson laboratory focuses on molecular and biochemical studies of two human genetic disorders, Huntington's disease and achondroplasia. Huntington's disease is a devastating neurological disorder caused by expansion of a CAG trinucleotide repeat within the coding region of the HD gene. It is one of a growing family of neurological disorders caused by triplet repeat expansion. Using Drosophila and inducible cell culture systems, we are creating cellular models of Huntington's disease in order to understand the pathogenesis of triplet repeats, as well as to utilize these models as screens for potential therapies.
The second goal of the lab is to understand the biological basis of achondroplasia, the most common genetic form of short-limbed dwarfism and one of several skeletal dysplasias caused by mutations in the fibroblast growth factor family of receptor tyrosine kinases. As part of a program project with Cedars Sinai and Dr. Ralph Bradshaw, we are investigating the effects of these mutations on signal transduction. The Thompson lab has also recently begun studies focusing on alterations in gene expression mediated by skeletal dysplasia mutations in FGFR3 using gene expression array technology.
Selected Publications:
L.M. Thompson, S. Plummer, M. Schalling, M.R. Altherr, J.F. Gusella, D.E. Housman, and J. J. Wasmuth (1991). A Gene Encoding a Fibroblast Growth Factor Receptor Isolated from the Huntington Disease Gene Region of Human Chromosome 4. Genomics 11, 1133-1142
Huntington's Disease Collaborative Research Group (1993). A Novel Gene Containing a Trinucleotide Repeat That is Expanded and Unstable on Huntington's Disease Chromosomes. Cell 72, 971-983.
R. Shiang*, L.M. Thompson*, Y.Z. Zhu, T. Fielder, D. Church, S. Winoker and J.J. Wasmuth (1994). Mutations in the Transmembrane Domain of FGFR3 Cause the Most Common Genetic Form of Dwarfism, Achondroplasia. Cell 78, 335-342.
P.L. Tavormina, R. Shiang, L.M. Thompson, Y.Z. Zhu, D.J. Wilkin, R.S. Lachman, W.R. Wilcox, D.L. Rimoin, D.H. Cohn and J.J. Wasmuth (1995). Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. Nature Genetics 9, 321-328.
L.M. Thompson, S. Raffioni, J.J. Wasmuth and R.A. Bradshaw (1997). Chimeras of the Native or Achondroplasia Mutant (G375C) of Human Fibroblast Growth Factor Receptor 3 Induce Ligand-Dependent Differentiation of PC12 Cells. Mol. and Cell Biology 17, 4169-4177.
S. Raffioni, Y.-Z. Zhu, R.A. Bradshaw and L.M. Thompson (1998). Effect of Transmembrane and Kinase Domain Mutations on FGFR3 Chimera Signaling in PC12 cells: A Model for the Control of Receptor Kinase Activation. J. Biol. Chem, 273, 35250-35259.
P.L. Tavormina, G.A. Bellus, M.K. Webster, M.J. Bamshad, A.E. Fraley, I. McIntosh, J. Szabo, W. Jiang, E.W. Jabs, W.R. Wilcox, J.J. Wasmuth, D.J. Donoghue, L.M. Thompson, and C.A. Francomano (1999). A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys-650-Met mutation in fibroblast growth factor receptor 3. Am. J. Hum. Genet. 64, 722-731.
J. Lawrence Marsh, Heli Walker, Heidi Theisen, Ya-Zhen Zhu, Tom Fielder, Judy Purcell and Leslie M. Thompson (1999). Expanded polyglutamine peptides alone are intrinsically cytotoxic and cause neurodegeneration in Drosophila. Hum. Mol. Genet. (2000) Vol 9, p 13-25.
