J. Lawrence MarshProfessor, Developmental & Cell Biology Director, Developmental Biology Center |
|
|
Research Interests |
Mechanisms of late onset Neurodegeneration - Oncogene signaling pathways in normal and abnormal growth. | |
|
Academic Distinctions | Fellow AAAS | |
|
Research Abstract |
We are engineering the fruit fly to express human neurodegenerative (and other) disease genes and using these animals to identify genetic mechanisms that affect disease and to identify possible therapeutics. Some therapeutics are now in clinical trials. We are also using the fly to uncover the mechanisms of oncogene regulation as it relates to the ability of tissues to regenerate and to become cancerous. These studies focus on mechanisms of cell signaling with particular emphasis on Wnts and BMPs. |
|
| Publications | Rockabrand, E., Slepko, N., Pantalone, A., Nukala, V. N., Kazantsev, A., Marsh, J. L., Sullivan, P. G., Steffan, J. S., Sensi, S. L. and Thompson, L. M. (2007). The 1st 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis. Hum Mol Genet. 6, 61-77 | |
| Theisen, H., Syed, A., Nguyen, BT., Lukacsovich, T., Purcell, J., Srivastava, GP., Iron, D., Gaudenz, K., Nie, Q., Wan, FYM., Waterman, ML., and Marsh, JL. (2007) Wingless Directly Represses DPP Morphogen Expression Via an Armadillo/TCF/Brinker Complex. PloS ONE 2(1): e142. doi:10.1371/journal.pone.0000142 | ||
| Marsh, J. L. and Thompson, L. M. (2006). Drosophila in the study of neurodegenerative disease. Neuron 52, 169-78. | ||
| Slepko, N., Bhattacharyya, AM., Jackson, GR., Steffan, JS., Marsh, JL., Thompson, LM. and Wetzel, R. (2006). Normal repeat length polyglutamine peptides accelerate aggregation nucleation and cytotoxicity of expanded polyglutamine proteins, PNAS 103, 14367-72 | ||
| Ehrnhoefer, D. E., Duennwald, M., Markovic, P., Wacker, J. L., Engemann, S., Roark, M., Legleiter, J., Marsh, J. L., Thompson, L. M., Lindquist, S. et al. (2006). Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington's disease models. Hum Mol Genet 15, 2743-51. | ||
| Desai, U. A., Pallos, J., Stockwell, B. R., Thompson, L. M., Marsh, J. L. and Diamond, M. I. (2006). Biologically Active Molecules that Reduce Polyglutamine Aggregation and Toxicity. Hum Mol Genet 15, 2114-2124. | ||
| Apostol, BL, Illes, K; Pallos, J; Bodai, L; Wu, J; Strand, A; , Schweitzer, E;, Olson, JM; Kazantsev, A; Marsh, JL and Thompson, LM (2006) Mutant Huntingtin alters MAPK signaling pathways in pc12 and striatal cells: ERK1/2 protects against mutant huntingtin-associated toxicity. Hum Mol Genet, 15:273-85 | ||
| Johnson, KG.; Tenney, AP; Ghose, A; Duckworth, AM; Higashi,M; Parfitt, K; Marcu, O; Heslip, TR; Marsh, JL; Schwarz, TL; Flanagan, JG; Van Vactor, D. (2006) The HSPGs Syndecan and Dallylike Bind the Receptor Phosphatase LAR and Exert Distinct Effects on Synaptic Development. Neuron, 49:517-531. | ||
| Nguyen A, Rosner A, Milovanovic T, Hope C, Planutis K, Saha B, Chaiwun B, Lin F, Imam SA, Marsh JL, Holcombe RF. (2005) Wnt pathway component LEF1 mediates tumor cell invasion and is expressed in human and murine breast cancers lacking ErbB2 (her-2/neu) overexpression. Int J Oncol. 27:949-56. | ||
| Mizutani CM, Nie Q, Wan FY, Zhang YT, Vilmos P, Sousa-Neves R, Bier E, Marsh JL, Lander AD. (2005) Formation of the BMP activity gradient in the Drosophila embryo. Developmental Cell 8,915-24. | ||
| Sousa-Neves, R., Lukacsovich, T., Mizutani, C.M., Locke, J., Podemski, L. and Marsh, J.L. (2005). High-resolution mapping of the Drosophila fourth chromosome using site-directed terminal deficiencies. Genetics 170, 127-38. | ||
| Wolfgang WJ, Miller TW, Webster JM, Huston JS, Thompson LM, Marsh JL, Messer A. (2005). "Suppression of Huntington's disease pathology in Drosophila by human single-chain Fv antibodies." PNAS 102(32): 11563-8. | ||
| Agrawal, N., Pallos, J., Slepko, N.,Apostol, B. L., Bodai, L., Chang, L., Chiang, A., Thompson, L. M., and Marsh, J. L. (2005) Identification of combinatorial drug regimens for treatment of Huntington’s disease using Drosophila. PNAS. 102, 3777-81 | ||
| Vilmos, V., Sousa-Neves, R., Lukacsovich, T. and Marsh, J.L. (2005) Crossveinless defines a new family of Twisted Gastrulation-like modulators of BMP signaling. EMBO reports 6, 262-267. | ||
| Zhang, X., Smith, D.L., Meriin, A.B., Engemann, S., Russel, D.E., Roark, M., Washington, S.L., Maxwell, M.M., Marsh, J.L., Thompson, L.M. Wanker, E.E., Young, A.B., Housman, D.E., Bates, G.P., Sherman, M.Y. and Kazantsev, A.G. (2005) A potent small molecule inhibits polyglutamine aggregation in Huntington's disease neurons and suppresses neurodegeneration in vivo. PNAS.102, 892-7 | ||
| Book Chapter: L.M. Thompson and J.L. Marsh (2004). Drosophila Models of Huntington Disease. In "Animal Models of Movement Disorders", Mark LeDoux, Ed. Academic Press. | ||
| Byun, T., Karimi, M., Marsh, J. L,, Milovanovic, T., Lin, F., and Holcombe, R.F. (2005) "Expression of secreted Wnt antagonists in gastrointestinal tissues: Potential role in stem cell homeostasis" J. Clin. Pathol., 58:515-519. | ||
| Chang, Y.T., Sharma, R., Marsh, J.L., McPherson, J.D., Bedell, J.A., Knust, A., Brautigam, C., Hoffmann, G.F. and Hyland, K. (2004) Levodopa-responsive aromatic L-amino acid decarboxylase deficiency. Ann Neurol, 55, 435-8. | ||
| Podemski, L., Sousa-Neves, R., Marsh, J.L. and Locke, J. (2004) Molecular mapping of deletion breakpoints on chromosome 4 of D. melanogaster. Chromosoma, 112:381-388. | ||
| Marsh JL, Thompson LM. (2004) Can flies help humans treat neurodegenerative diseases? Bioessays, 26, 485-496 | ||
| Rockabrand, E., Slepko, N., Pantalone, A., Nukala, V. N., Kazantsev, A., Marsh, J. L., Sullivan, P. G., Steffan, J. S., Sensi, S. L. and Thompson, L. M. (2007). The 1st 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis. Hum Mol Genet. 6, 61-77 | ||
| Milovanovic, T., Planutis, K., Nguyen, A., Marsh, J. L., Lin, F., Hope, C., and Holcombe, R.F. (2004) Expression of Wnt Genes and Frizzled 1 & 2 Receptors in Normal Breast Epithelium and Infiltrating Breast Carcinoma, International Journal of Oncology, 25:1337-42 | ||
| Steffan, J.S., Agrawal, N., Pallos, J., Rockabrand, E., Trotman, L.C., Slepko, N., Illes, K., Lukacsovich, T.,Zhu, Y.Z., Cattaneo, E., Pandolfi, P.P., Thompson, L.M., Marsh, J.L. (2004) Huntington is SUMO-1 Modified: Implications for Huntington's Disease Pathogenesis. Science, 304: 100-104. | ||
| Steffan, J.S., Bodai, L., Pallos, J., Poelmann, M., Apostol, B.L., Kazantsev, A., Schmidt, E., Zhu, Y., Greenwald, M., Kurokawa, R., Housman, D.E., Jackson, G.R., Marsh, J.L. and Thompson, L.M. (2001) Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila Nature 413:739-743. | ||
| Marsh J.L., Thompson L.M. (2004) Can flies help humans treat neurodegenerative diseases? | ||
| Marsh J.L., Walker, H., Theisen, H., Zhu, Y., Fielder, T., Purcell, J and Thompson, L.M. (2000) Expanded polyglutamine peptides alone are intrinsically cytotoxic and cause neurodegeneration in Drosophila. Human Molecular Genetics, 9:13-25 | ||
| Hockly, E., Richon, V.M., Woodan, B., Smith D.L., Zhou, X., Rosa, E., Ghazi-Noori, S., Sathasivam, K., Mahal, A., Lowdem, P.A.S., Steffan, J.S., Marsh, J.L., Thompson, L.M., Lewis, C.M., Marks, P.A. and Bates, G.P. (2003) Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in the R6/2 mouse model of Huntington's Disease. PNAS 100,2041-6. | ||
| Ross, J.J., Shimmi, O., Vilmos, P., Petryk, A., Kim, H., Gaudenz, K., Hermanson, S., Ekker, S.C., O'Connor, M.B. and Marsh, J.L. (2001) Twisted gastrulation is a conserved extracellular BMP antagonist. Nature 410, 479-83. | ||
| Hovanes, K.H., J.E. Munguia, T. Truong, T. Milovanovic, T.W.H. Li, J.L. Marsh, R.F. Holcombe and M.L. Waterman (2001) Selective expression of B-catenin-sensitive forms of Lymphoid Enhancer Factor-1 in colon cancer. Nature Genetics 29, 53-57. | ||
| Theisen, H., Haerry, T.E., O'Connor, M.B. and Marsh J.L. (1996) Developmental territories created by mutual antagonism between WG and DPP Development 122: 3939-3948. | ||
| Chang, Y.T., Sharma, R., Marsh, J.L., McPherson, J.D., Bedell, J.A., Knust, A., Brautigam, C., Hoffmann, G.F. and Hyland, K. (2004) Levodopa-responsive aromatic L-amino acid decarboxylase deficiency. Ann Neurol, 55, 435-8. | ||
| Sousa-Neves, R., Lukacsovich, T., Mizutano, C.M., Locke, J. and Marsh, J.L. (2004) Synthesis of Nested Terminal Deficiencies that subdivide Region 102B1-102D6 on the Fourth Chromosome of Drosophila melanogaster. Genetics, In Press. | ||
| Pollitt, S.K., Pallos, J., Desai, U.A., Ma, A.A., Thompson, L.M., Marsh J.L. and Diamond, M.I. (2003) A High-throughput FRET-based Assay of Intracellular Polyglutamine Protein Aggregation Implicates a Novel Cellular Regulatory Pathway. Neuron, 40, 685-94. | ||
| Grants | R01 HD36081 Molecular Basis of Cell Interactions 6/1/97 - 5/31/06 - PI | |
| NINDS 1 R01 NS045283-01 Role of Protein Acetylation in Huntington's Disease 12/1/02 - 11/30/07 - PI | ||
| DMS/NIGMS Morphogen Systems: A Joint Math and Experimental Investigation 7/01/02 - 6/30/06 - As Co-PI | ||
| RFA GM-01-001 Transport and Complexity in Biological Systems 7/01/02 - 6/30/05 - As Co-PI | ||
| HDG-24085 Cure HD Initiative 2/1/97 - 6/30/05 - Co-PI | ||
| Huntington Disease Society of America 30057 Alterations in Acetylation and Transcription in HD - Co-PI | ||
| Hereditary Disease Foundation HDF-24085 Co-Pi | ||
|
Professional Societies |
Society of Human Genetics Genetics Society of America |
|
| Other Experience |
Chair, Dept. of Developmental and Cell Biology, Univ. of Calif., Irvine 1997—2000 |
|
| Graduate Programs |
Developmental Biology and Genetics Cancer Biology |
|
| Research Center | Developmental Biology Center http://dbc.bio.uci.edu/ | |
| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=2721 | |
| Last updated | 06/21/2007 | |