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J. Lawrence Marsh

Professor, Developmental & Cell Biology
School of Biological Sciences

Director, Developmental Biology Center
School of Biological Sciences

PH.D., University of Washington, 1974

Phone: (949) 824-6677, 3226
Fax: (949) 824-3571
Email: jlmarsh@uci.edu

University of California, Irvine
4244 McGaugh Hall
Mail Code: 2300
Irvine, CA 92697

picture of J. Lawrence  Marsh

Mechanisms of late onset Neurodegeneration - Oncogene signaling pathways in normal and abnormal growth.
Fellow AAAS
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.
Available Technologies
Publications Bodai, L. and Marsh, J. L. (2012) A crucial target in Huntington's disease: ERK at the crossroads of signaling, Bioessays In Press.
  Bodai, L., Pallos, J., Thompson, L. M. and Marsh, J. L. (2011) 'Pcaf modulates polyglutamine pathology in a Drosophila model of Huntington's disease', Neurodegenerative Diseases In Press: Ms #: 201101006
  Sleiman, S. F., Langley, B. C., Basso, M., Berlin, J., Xia, L., Payappilly, J. B., Kharel, M. K., Guo, H. C., Marsh, J. L., Thompson, L. M., Mahishi, L., Ahuja, P., MacLellan, W. R., Geschwind, D. H., Coppola, G., Rohr, J. and Ratan, R. R. (2011) Mithramycin Is a Gene-Selective Sp1 Inhibitor That Identifies a Biological Intersection between Cancer and Neurodegeneration, Journal of Neuroscience 31(18): 6858-6870.
  Maher, P., Dargusch, R., Bodai, L., Gerard, P. E., Purcell, J. M. and Marsh, J. L. (2011). ERK activation by the polyphenols fisetin and resveratrol provides neuroprotection in multiple models of Huntington's disease. Hum Mol Genet 20, 261-70. PMID:20952447 [PubMed - in process] PMCID: PMC3005900
  Kayed, R., Canto, I., Breydo, L., Rasool, S., Lukacsovich, T., Wu, J., Albay, R., Pensalfini, A., Yeung, S., Head, E., Marsh, J. L. and Glabe, C. (2010). Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Abeta oligomers. Mol Neurodegener 5, 57. PMID:21144050 [PubMed - in process] PMCID: PMC3019145
  Luthi-Carter, R., Taylor, D. M., Pallos, J., Lambert, E., Amore, A., Parker, A., Moffitt, H., Smith, D. L., Runne, H., Gokce, O., Kuhn, A., Xiang, Z. M., Maxwell, M. M., Reeves, S. A., Bates, G. P., Neri, C., Thompson, L. M., Marsh, J. L. and Kazantsev, A. G. (2010). SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A 107, 7927-32.
  McConoughey, S. J., Basso, M., Niatsetskaya, Z. V., Sleiman, S. F., Smimova, N. A., Langley, B. C., Mahishi, L., Cooper, A. J. L., Antonyak, M. A., Cerione, R. A., Li, B., Starkov, A., Chaturvedi, R. K., Beal, M. F., Coppola, G., Geschwind, D. H., Ryu, H., Xia, L., Iisma, S. E., Pallos, J., Pasternack, R., Hils, M., Fan, J., Raymond, L. A., Marsh, J. L., Thompson, L. M. and Ratan, R. R. (2010) 'Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington's disease', Embo Molecular Medicine 2(9): 349-370.
  Ossato, G., Digman, M. A., Aiken, C., Lukacsovich, T., Marsh, J. L. and Gratton, E. (2010). A two-step path to inclusion formation of huntingtin peptides revealed by number and brightness analysis. Biophys J 98, 3078-85.
  Thompson, L. M., Aiken, C. T., Kaltenbach, L. S., Agrawal, N., Illes, K., Khoshnan, A., Martinez-Vincente, M., Arrasate, M., O'Rourke, J. G., Khashwji, H., Lukacsovich, T., Zhu, Y. Z., Lau, A. L., Massey, A., Hayden, M. R., Zeitlin, S. O., Finkbeiner, S., Green, K. N., LaFerla, F. M., Bates, G., Huang, L., Patterson, P. H., Lo, D. C., Cuervo, A. M., Marsh, J. L. and Steffan, J. S. (2009). IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome. J Cell Biol 187, 1083-99. PMID: 20026656
  Sinadinos, C., Burbidge-King, T., Soh, D., Thompson, L. M., Marsh , J. L., Wyttenbach, A. and Mudher, A. K. (2009). Live axonal transport disruption by mutant Huntingtin fragments in Drosophila motor neuron axons. Neurobiol Dis 34, 389-95. PMID: 19268537
  Najdi, R., Syed, A., Arce, L., Theisen, H., Ting, J. H., Atcha, F., Nguyen, A. V., Martinez, M., Holcombe, R. F., Edwards, R. A., Marsh*, J. L. and Waterman*, M. L. (2009). A Wnt kinase network alters nuclear localization of TCF-1 in colon cancer. Oncogene 28, 4133-46. PMID: 19749792
  Aiken, C.T., Steffan, J.S., Guerrero, C.M., Khashwji, H., Lukacsovich, T., Simmons, D., Purcell, J.M., Menhaji, K., Zhu, Y.Z., Green, K., Laferla, F., Huang, L., Thompson, L.M. and Marsh, J.L. (2009). Phosphorylation of threonine 3: implications for Huntingtin aggregation and neurotoxicity. J Biol Chem 284, 29427-36. PMID: 19710014
  Iron, D., Syed, A., Theisen, H., Lukacsovich, T., Mehrangiz, N., Marsh, J., Wan, F. and Nei, Q. (2008). The role of feedback in the formation of morphogen territories. Mathematical biosciences and engineering 5, 277-298.
  Apostol, B. L., Simmons, D. A., Zuccato, C., Illes, K., Pallos, J., Casale, M., Conforti, P., Ramos, C., Roarke, M., Kathuria, S. Cattaneo, E., Marsh, J. L. and Thompson, L. M. (2008). CEP-1347 reduces mutant huntingtin-associated neurotoxicity and restores BDNF levels in R6/2 mice. Mol Cell Neurosci 39, 8-20. PMID: 18602275
  Theisen, H., Syed, A., Nguyen, B. T., Lukacsovich, T., Purcell, J., Srivastava, G. P., Iron, D., Gaudenz, K., Nie, Q., Wan, F. Y., Waterman, M. L. and Marsh, J. L. (2007). Wingless Directly Represses DPP Morphogen Expression via an Armadillo/TCF/Brinker Complex. PLoS ONE 2, e142. PMID: 17206277
  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 first 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis. Hum Mol Genet 16, 61-77. PMID: 17135277
  Atcha, F. A., Syed, A., Wu, B., Hoverter, N. P., Yokoyama, N. N., Ting, J. H., Munguia, J. E., Mangalam, H. J., Marsh, J. L. and Waterman, M. L. (2007). A unique DNA binding domain converts T-cell factors into strong Wnt effectors. Mol Cell Biol 27, 8352-63. PMID: 17893322
  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
  Marsh, J.L., Lukacsovich, T. and Thompson, L. M. (2009). Animal models of polyglutamine diseases and therapeutic approaches. J Biol Chem 284, 7431-5. PMID: 18957429
  Pallos, J., Bodai, L., Lukacsovich, T., Purcell, J. M., Steffan, J.S., Thompson, L.M. and Marsh, J.L. (2008). Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington's disease. Hum Mol Genet 17, 3767-75. PMID: 18762557
  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 first 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis. Hum Mol Genet 16, 61-77. PMID: 17135277
  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 5R01NS45283, Marsh (PI) 12/01/02-11/30/15 NIH/NINDS ADC
Role of chromatin remodeling in Huntington’s disease Marsh PI 02/01/11-05/31/11 NIH/NINDS ADC
SB 48483 Marsh (PI) 03/30/10-12/31/12 Siena Biotech (contract) Evaluation of novel compounds for Huntington’s therapeutics
U01-NS063953, Gottesfeld (PI)/Marsh (PI, UC Subcontract) 04/01/10-03/31/13 Scripps/ NIH ADC Novel HDAC Inhibitors as Therapeutics for Huntington's Disease
3R01NS052789 L.Thompson (PI)/Marsh (Co-I) 06/01/06 - 03/31/11 NIH-NINDS ADC Pathogenic impact of SUMO modification in Huntington’s disease
HQ-44670, Marsh(PI) 11/1/08-10/31/10 High Q Foundation ADC Relevance of proteolytic processing to Htt toxicity
P50GM076516, Lander PI/Marsh Theme Leader-PI 08/01/07-07/31/12 NIH/NIGMS ADC Systems Biology of Morphogenesis and Spatial Information Flow
3P30 CA062203-14, MeyskensPI/ Marsh Director OptBiolCore 08/01/02-01/31/12 NIH/NCI Cancer Center Support Grant (Optical Biology Core Facility)
5R01CA096878 Waterman (PI)/ Marsh Collaborator 06/01/08-04/30/13 NIH ADC LEF/TCF Expression in Colon Cancer Role: Collaborator
KF-50242, Gratton (PI)/ Marsh; Digman CoPIs 01/01/11-12/31/13 Keck foundation Development of an in vivo Nanoscale Optical Imager
RR027508-01A1, Digman (PI) 04/01/11- 03/31/12 NIH/NCRR Shared instrumentation grant for the purchase of a Zeiss 780 confocal Microscope for the OBC . (MCBU)
NIH RO1 HD36081 Marsh (PI) 6/1/97 - 5/31/08 Molecular Basis Of Cell Interactions NIH RO1 HD36081 Marsh (PI) 6/1/97 - 5/31/08 Molecular Basis Of Cell Interactions
HiQ Foundation Glabe (PI)/Marsh (Co-PI) 11/1/05 - 10/31/06 Htt oligomers as therapeutic targets
HiQ Foundation Thompson (PI)/Marsh (Co-PI) 2/1/97 - 9/30/06 Development of Therapeutics for Huntington’s disease
DMS/NIGMS Math.Bio Initiative GM 67247 Marsh (Co-PI) 07/01/02 - 6/30/06 Morphogen Systems: A joint Math and Experimental Investigation
HDSA-30057 L.Thompson (PI)/Marsh (Co-PI) 11/1/01-12/31/06 Alterations in Acetylation and Transcription in HD
HDF-24085 Thompson (PI)/Marsh (Co-PI) 2/1/97-6/30/06 Hereditary Disease Foundation Cure HD Initiative
RFA NIH GM-01-001 Lander (PI)/Marsh (Co-PI) P20 07/01/02 - 6/30/05 Centers of Excellence in Complex Biomedical Systems Research Transport and Complexity in Biological Systems
NIH RO1 HD36049 Marsh (PI) 01/01/98 - 6/30/02 In Vivo Role Of Proteoglycans In Growth Factor Signaling
California Breast Cancer Res Prog Holcombe (PI) / Marsh (Co-PI) 07/01/00 – 06/30/02 Wnt signaling in breast cancer: Translational Studies
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
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 01/13/2012