Publications and Presentations
PAPERS
1) Schmidt, K., Alper, S., and Stringham, E. G. The Neuron Navigator Homolog UNC-53 functions in p38 MAPK/PMK-1 and FOXO/DAF-16 Signalling in Innate Immunity. Manuscript in preparation, expected submission December 2010.
Immunity in C. elegans depends on several conserved and independent signalling pathways, including the p38/PMK-1 mitogen-activated protein kinase (MAPK) and insulin-like FOXO/DAF-16 pathways. Here we show that the cell migration protein UNC-53/NAV2has a novel post-developmental role in the control of innate immunity. Additionally, decreased expression of several antimicrobial genes show that unc-53 regulates the production of effectors controlled by both pmk-1 and daf-16. Analysis of unc-53 synaptic function as measured by Aldicarb sensitivity show that unc-53 animals are hypersecretory, suggesting that unc-53 may partially exert its effect through the neuroendocrine secretion of immune effectors. Tissue-specific RNAi and rescue experiments using heterologous promoters driving unc-53 expression in the intestine or neurons indicate that neither tissue appears to be the exclusive site of unc-53 activity. Taken together, our data suggests a model whereby unc-53 is a key regulator of innate immunity functioning in multiple tissues and genetic pathways.
2) Marcus, N., and Stringham, E.G. The Rac-GEF UNC-73/TRIO Mediates Multiple and Genetically Distinct Pathways to regulate cell migration in C. elegans. In preparation, expected submission January 2011.
The cytoskeleton regulator UNC-53/NAV2is required for both the anterior and posterior outgrowth of several neurons as well as that of the excretory cell (Stringham, et al., 2002; Schmidt et al., 2009) while the kinesin like motor VAB-8is essential for most posteriorly directed migrations in C. elegans (Wightman et al., 1996). Genetic analysis directed at putative interactors of UNC-53 or VAB-8, together with cell specific rescue experiments, suggest that VAB-8, SAX-3/ROBO, SLT-1/Slit and EVA-1 are functioning together in the outgrowth of the excretory canals, while UNC-53 appears to function in a parallel pathway with UNC-71/ADAM. The known VAB-8 interactor UNC-73/TRIO operates in both pathways, as it exhibits enhancement of the canal defects in double mutant combination with either UNC-53 or VAB-8. Our current hypothesis is that together with UNC-53/NAV2 and UNC-71/ADAM, UNC-73/Trio functions cell autonomously within the excretory cell to promote outgrowth while also maintaining a cell non-autonomous function through partnering with VAB-8 and the receptors SAX-3 and EVA-1.
3) Stringham, E.G. and Schmidt, K. Navigating the cell: UNC-53 and the navigators, a family of cytoskeletal regulators with multiple roles in cell migration, outgrowth, and endocytosis. (2009) Cell Adhesion and Migration, 3(4): 342-6. (1 citation as of September 21, 2010)
I was invited to write this Commentary and View article discussing the cell biology of UNC-53 and the Navigators for the journal Cell Adhesion and Migration. This paper also contained some new data from my lab demonstrating the role of unc-53 in endocytosis.
4) Schmidt, K., Marcus-Gueret, N., Adeleye, A., Webber, J., Baillie, D. and Stringham, E. G. The cell migration molecule UNC-53/NAV-2 is linked to the ARP2/3 complex by ABI-1. (2009) Development, 136:563-574. (4 citations as of September 21, 2010)
This paper identifies UNC-53/NAV2 as a novel molecular partner of ABI-1, a key regulator of Arp2/3 mediated actin filament assembly. We found that a restricted CH domain of UNC-53 is sufficient to bind ABI-1 and that disruption of this interaction impairs longitudinal guidance. Migration defects were also observed in RNAi of proteins known to function with abi-1 in actin dynamics including nck-1, wve-1 and arx-2. We propose that UNC-53/NAV2, through its CH domain, acts as a scaffold that links ABI-1 to the ARP2/3 complex to regulate actin cytoskeleton remodeling. Despite its publication only this year, this paper has already been cited in a review article on actin dynamics by Insall and Machesky (2009, Developmental Cell 17: 310-322).
5) Stringham, E.G., N. Pujol, J. Vandekerkchove and T. Bogaert. Unc-53 controls longitudinal migration in C. elegans. (2002) Development, 129:3367-3379. (35 citations as of September 21, 2010)
This paper describes the genetics and function of UNC-53/NAV2, a novel component of a signal transduction pathway controlling cell motility and growth cone extension in the longitudinal axis of C. elegans. The journal Development consistently ranks in the top 5 for impact in the field of developmental biology. This paper was also selected as a “must read” by the Faculty of 1000. While most of the experiments were completed during my Post-Doc in Belgium, some control experiments and data were collected at Trinity Western University and supported by my NSERC Discovery grant. The discovery of a family of orthologous genes in humans, coined NAV (neuronal navigator), underscores the importance of this pathway (Merrillet al., 2002, PNAS 99:3422-3427; Maes et al., 2002, Genomics, 80:21-30). For example, loss of human NAV 3 is associated with a poor prognosis in certain types of lymphoma suggesting that NAV 3 may act as a tumour suppressor (Karenko et al., 2005, Cancer Res 65:8101-10).
6) Stringham, E.G. Teaching future scientists and physicians to think about cancer treatment, spiritually. (2002) Selected Proceedings on Searching for Meaning in the New Millennium. INPM Press.
7) Mutwakil, M.H.A.Z, J.P. Reader, D.M. Holdich, P.R. Smithurst, E.P.M. Candido, D. Jones, E.G. Stringham and D.I. de Pomerai. (1997) Use of stress inducible transgenic nematodes as biomarkers of heavy metal pollution in water samples from an English river system. Arch. Env. Contam.Toxicol. 32: 146-153. (53 citations as of September 21, 2010)
8) Jones, D., E.G. Stringham, S.L. Babich and E.P.M. Candido. (1996) Captan induces the stress response and inhibits feeding in a nematode biomonitor. Toxicol. 109: 119-127. (50 citations as of September 21, 2010)
9) Jones, D., E.G. Stringham, R.W. Graham and E.P.M. Candido. (1995) A portable regulatory element directs gonad specific expression of the Caenorhabditis elegans ubiquitin gene ubq-2. Devel. Biol. 171: 60-72. (11 citations as of September 21, 2010)
10) Stringham, E.G. and E.P.M. Candido. (1994) Transgenic hsp16-lacZ strains of the soil nematode Caenorhabditis elegans as biological monitors of environmental stress. Environ. Toxicol. Chem. 13:1211-1220. (94 citations as of September 21, 2010)
The paper describes the creation of a novel and sensitive transgenic bioassay to detect a variety of environmental stressors including heavy metals and pesticides. These environmentally relevant compounds were shown to induce the stress response at sub-lethal levels, making this a more sensitive assay than the corresponding LC50 assay commonly used.The simplicity of this assay makes it a valuable tool for student projects and I have incorporated it several times in undergraduate teaching in biotechnology and applied ecology.
11) Stringham, E.G. and E.P.M. Candido. (1993) Targeted single-cell induction of gene products in Caenorhabditis elegans: A new tool for developmental studies. J. Exp. Zool. 266: 227-233. (46 citations as of September 21, 2010)
This paper describes a novel approach to achieve cell specific or mosaic expression of gene products in C. elegans. Taking advantage of the transparency of C. elegans, a coumarin dye laser was used to induce the expression of a reporter coding region under control of a heat shock promoter in single cells. This article has been cited in 46 papers where laser induced heat shock was used as a tool in developmental studies of zebrafish, butterfly, Drosophila, Arabidopsis and C. elegans. In one application, Kurup et al (2005, Plant Journal, 42:444-453) used a laser to induce the expression of a hsp-transposable element, triggering excision and activation of a fluorescent marker in the target cell and its progeny, thereby labeling a specific cell lineage in living plants.
12) Stringham, E.G., D. Jones and E.P.M. Candido. (1992) Analysis of polyubiquitin gene (ubq-1) expression in transgenic Caenorhabditis elegans. Gene 113: 165-173. (13 citations as of September 21, 2010)
13) Stringham, E.G., D.K. Dixon, D. Jones and E.P.M. Candido (1992). Temporal and spatial expression patterns of the small heat shock (hsp16) genes in transgenic C. elegans. Molec. Biol. Cell. 3: 221-233. (205 citations as of September 21, 2010)
This paper demonstrated that the hsp16 genes are regulated in a strictly stress-inducible, tissue-general manner and represents one of the first promoter studies done in C. elegans. These tightly regulated promoters are now widely available throughout the C. elegans research community and are used to study gene function.
PATENTS:
Bogaert, T., Stringham, E.G. and J. Vandekerckhove. “UNC-53 from C. elegans and its uses in testing compounds involved in the control of cell behaviour and pharmaceutical compositions.” International Patent (WO/1996/038555)
Candido, E.P.M., Stringham, E.G. and D. Jones. “Biological systems incorporating stress-inducible genes and reporter constructs for environmental biomonitoring and toxicolgy”. Patent issued March 2, 1999) U.S. Patent No. 5,877,398.
THESES:
Stringham, E.G. Temporal and spatial expression patterns of the hsp-16 and ubq-1 genes in transgenic C. elegans. 1992. Ph.D. Dissertation, Genetics Program, University of British Columbia.
Stringham, E.G. Gene mapping studies of chromosome 8 in man. MSc. Dissertation. Human Genetics, University of Mainitoba.
CONFERENCE PRESENTATIONS
Schmidt, K.L., Alper, S. and Stringham, E.G. The Neuron Navigator Homolog UNC-53 functions in p38 MAPK/PMK-1 and FOXO/DAF-16 Signalling in Innate Immunity. American Society of Cell Biology 50th Annual Meeting, December 11-15, 2010, Philadelphia, PA.
Marcus, N., and Stringham, E.G. The Rac-GEF UNC-73/TRIO Mediates Multiple and Genetically Distinct
Pathways to regulate cell migration in C. elegans. American Society of Cell Biology 50th Annual Meeting, December 11-15, 2010, Philadelphia, PA.
Ramsay, L. and Stringham, E.G. Do worms go grey? Examining the role of the small heat shock protein, HSP-12.6 in stress and ageing in Caenorhabditis elegans.
American Society of Cell Biology 50th Annual Meeting, December 11-15, 2010, Philadelphia, PA.
Dubuke, M., Grant,C, Sullivan-Keiser, J., O’Toole, S., Jennifer Gosselin, J., Kristopher L. Schmidt, K., Stringham, E.G., Ryder, E.F. The MRL signaling protein MIG-10/Lpd interacts with ABI-1 during guided migrations in C. elegans. 68th Annual Society for Developmental Biology Meeting, July 23-27, 2009, San Francisco, CA.
Schmidt, K., Stringham, E.G. Molecular interactions reveal multiple roles for UNC-53 in cell migration, intracellular trafficking, and innate immunity. Abstract #74, 17th International C. elegans Meeting, Los Angeles, CA, June 24-28, 2009. (This abstract was selected for a platform presentation.)
Ramsay, L., Stringham, E.G. Determining the Role of the Small Heat Shock Protein HSP12.6 in C. elegans. Abstract # 390, 17th International C. elegans Meeting, Los Angeles, CA, June 24-28, 2009.
Marcus, N., and Stringham, E. Examining the roles of unc-53 and vab-8 in longitudinal migration. Abstract # 1050, 17th International C. elegans Meeting, Los Angeles, CA, June 24-28, 2009. (This poster won 3rd prize in its division at this conference.)
Schmidt, K., Marcus, N., Adeleye, A., Webber, J., Baillie, D., and Stringham, E.G. The Cell Migration Molecule UNC-53/NAV-2 is linked to the Arp2/3 Complex by ABI-1. Abstract # 246. American Society of Cell Biology 48th Annual Meeting, December 13-17, 2008, San Francisco, CA.
Marcus, N., and Stringham, E.G. UNC-53 functions independently of VAB-8 to control cell migration, Abstract # 2481. American Society of Cell Biology 48th Annual Meeting, December 13-17, 2008, San Francisco, CA.
Schmidt, K., Marcus, N., Adeleye, A., Webber, J., Baillie, D., and Stringham, E.G. The Cell Migration Molecule UNC-53/NAV-2 is linked to the Arp2/3 Complex by ABI-1., Canadian Developmental Biology Symposium, February 28-March 2, 2008, Banff, Alberta.
Marcus, N., and Stringham, E.G. UNC-53 functions independently of VAB-8 to control cell migration., Canadian Developmental Biology Symposium, February 28-March 2, 2008 , Banff, Alberta.
Kreiter, E., and Stringham, E.G. Identification of genes involved in vesicle trafficking in C. elegans. Murdock Undergraduate Conference, November 2-3, 2007, Willamette University, Oregon.
Stringham, E.G., Schmidt, K., Marcus, N., Webber, J., Adeleye, A. The cell migration molecule UNC53/NAV2 binds ABI-1 and is involved in endocytic pathways in C. elegans. Presented at “Dynamic interplay between cytoskeletal and membrane systems”, ASCB and the European Cytoskeleton Forum, June 27-30, 2007, Dijon, France.
Schmidt, K., Marcus, N., Webber, J., Zhao,Z., Baillie, D., and Stringham, E.G. UNC53/NAV2 is linked to the Arp 2/3 complex by Abelson kinase interactor. “Sixteenth International C. elegans meeting”, a conference sponsored by the Genetics Society of America, June 27-July 1, 2007, Los Angeles, USA. (This poster won 2nd prize in its division at this conference.)
Marcus, N., and Stringham, E.G. Examination of the roles between vab-8 and unc-53 in posterior cell migrations. “Sixteenth International C. elegans meeting”, a conference sponsored by the Genetics Society of America, June 27-July 1, 2007, Los Angeles, USA.
Schroeder, C. and Stringham, E.G. (2006) Sugar and stress: The effect of mutations in insulin signaling on heat shock protein expression in C. elegans. Murdock Undergraduate Research Conference, Portland, OR.
Schmidt, K., Marcus, N., Webber, J., and Stringham, E.G. (2006) The cell migration molecule UNC-53/NAV2 is linked to endocytosis in C. elegans. Murdock Undergraduate Student Research Conference, Portland, OR.
K.L.Schmidt, N.Marcus, D.Baillie and Stringham, E.G.. (2006) The Cell Migration Molecule UNC-53/NAV-2 Interacts with C.elegans Verprolin and Abelson Kinase Interactor. Society for Developmental Biology Northwest Regional Meeting, Friday Harbour, WA.
K.L.Schmidt, N.Marcus, D.Baillie and Stringham, E.G.. (2005) The Cell Migration Molecule UNC-53/NAV-2 Interacts with C.elegans Verprolin and Abelson Kinase Interactor. 15th Biennial International C.elegans Conference. Los Angeles.
Adeleye, A., Grainger, S., Baillie, D. and Stringham, E.G.(2004) UNC-53 controls longitudinal migration and interacts with regulators of the actin cytoskeleton. Canadian Developmental Biology Symposium, Banff, Alberta.
Stringham, E.G. (2004) UNC-53/NAV2 controls longitudinal migration and interacts with regulators of the actin cytoskeleton. British Columbia Cell Biology Retreat, Loon Lake, BC.
Stringham, E.G. (2004) DNA workshops for Middle and Secondary teachers. Building bridges to the world:Maple Ridge Teachers Association Annual Convention, February 18, 2004, Maple Ridge, BC.
Adeleye, A., Grainger, S., Baillie, D. and Stringham, E.G. The N-terminus of UNC-53 interacts with regulators of the actin cytoskeleton. (2003) Abstract No.501C, International C.elegans meeting, Los Angeles, California.
Stringham, E.G. (2002) Teaching future scientists and physicians to think about cancer treatment, spiritually. Selected Proceedings on Searching for Meaning in the New Millennium. INPM Press.
Adeleye, A., Grainger, S., Baille, D. and Stringham, E.G. (2002) Extending the unc-53 pathway-Part I: Yeast two hybrid reveals interactors. Abstract No. 107, West Coast C.elegans meeting, San Diego, California.
Stauffer, A.C., Van Dorp, N. and Stringham, E.G. (2002) Extending the unc-53 pathway-Part II: Isolation of genetic suppressors. Abstract No. 108, West Coast C. Elegans meeting, San Diego, California.
Adeleye, A., Vedulla, F. and Stringham, E.G. (2001) Identification of genes controlling longitudinal guidance in the nematode C. elegans. Abstracts to the Society for Developmental Biology Annual Meeting, Seattle, WA. Devel. Biol. 235:184.
Stringham, E.G. (2000) Teaching future scientists and physicians to think about cancer treatment, spiritually. Searching for Meaning in the New Millenium, Richmond, B.C.
Buesa, C., P. Verhasselt, M. De Raeymaeker, L. Maertens, C. Platteeuw, J. Geysen, K. VerDonck, M. Van de Craen, E. Stringham and T. Bogaert. (1999) Steerins (unc-53) in health and disease: from C. elegans gene to drug discovery. International C. elegans meeting abstracts # 872. Madison WI.
Buesa, C., I. Maillet, E. G. Stringham, J. Vandekerckhove and T. Bogaert (1996) Unc-53 and growth cone steering in the anteroposterior axis: genetic and biochemical characterization and identification of genes in the pathway. Abstracts to the Second European Worm Meeting, Strasbourg, France.
Buesa,C., E.G. Stringham, J. Vandekerckhove and T. Bogaert. (1996) Caenorhabditis elegans UNC-53: a novel component of the SEM-5/GRB2 signal transduction pathway, binds F-actin and SEM-5. Keystone Symposium on Signal Transduction Through Tyrosine Kinases., Taos, NM.
Stringham, E.G., N. Van de Steene, J. Vandekerckhove and T. Bogaert. (1995) Unc-53 controls growth cone steering in the a/p axis and encodes a putative nucleotide binding protein that binds SEM-5 and the actin cytoskeleton. International Caenorhabditis elegans meeting. Madison, WI., p. 17.
Candido, E.P.M., D. Jones and E.G. Stringham. (1995) Visualization and quantification of environmentally-induced stress in a whole multicellular organism. Keystone Symposium on Heat Shock (Stress) Proteins in Biology and Medicine, Santa Fe, NM.
Candido, E.P.M., D. Jones and E.G. Stringham. (1994) Use of transgenic strains of the nematode Caenorhabditis elegans for toxicological and environmental monitoring. 27th Annual Symposium of the Soc. Toxicology of Canada, Montreal, Que.
Candido, E.P.M. and E.G. Stringham. (1994) Testing of xenobiotics and environmental samples using stress-inducible transgenic strains of the nematode,Caenorhabditis elegans. Congress on Cell and Tissue Culture, Research Triangle Park, NC.
Candido, E.P.M. and E.G. Stringham. (1994) Visualizing the stress response in a whole multicellular organism. Cold Spring Harbor Meeting on The Biology of Heat Shock Proteins and Molecular Chaperones, p. 49.
Stringham, E.G. and E.P.M. Candido. (1993) Characterisation of the stress response using transgenic hsp16-lacZ strains. American Society of Biochemistry and Molecular Biology, San Diego, CA. FASEB J.
Stringham, E.G. and E.P.M. Candido. (1993) Characterisation of the stress response using transgenic hsp16-lacZ strains. International C. elegans meeting. Madison, WI., p. 428.
Stringham, E.G. and E.P.M. Candido. (1992) Use of transgenic strains of the nematode Caenorhabditis elegans as biological monitors of environmental stress. Society of Environmental Toxicology and Chemistry meeting. Cincinnatti, OH.
Stringham, E.G. and E.P.M. Candido. (1992) Induction of the heat shock response in individual cells of C. elegans using a laser microbeam. Abstracts of the West Coast C. elegans meeting. San Francisco, CA.
Candido, E.P.M., E.G. Stringham and D. Jones. (1991) Expression of hsp16-lacZ fusions in transgenic Caenorhabditis elegans. Abstracts to Stress Proteins and the Heat Shock Response. Cold Spring Harbour, NY., p. 72.
Stringham, E.G., D. Jones and E.P.M. Candido. (1991) Expression of ubq-1-lacZ fusions in transgenic Caenorhabditis elegans. International C. elegans meeting. Madison, WI. ,p. 305.
Stringham, E.G., D. Jones and E.P.M. Candido. (1991) Differential expression of hsp16-lacZ fusions in transgenic Caenorhabditis elegans. International C. elegans meeting. Madison, Wi., p.261.
Candido, E.P.M., E.G. Stringham and D. Jones. (1990) Hsp16 and ubq-1 expression in Caenorhabditis elegans. American Society for Biochemistry and Molecular Biology meeting abstracts. New Orleans, Louis. FASEB J. 4: A2130.
Stringham, E.G. and E.P.M. Candido. (1989) Transformation of C. elegans with hsp16b-galactosidase gene fusions. Cold Spring Harbor Meeting on Caenorhabditis elegans, p.29.
McAlpine, P.J.M., E.G. Stringham and P.W. Allerdice. (1987). The GPT locus expressed in erythrocytes does not lie at the breakpoint of an inv(8)(p23q22). Cytogen.Cell Genet. 46:659.
Invited Academic Presentations:
British Columbia Cell Biology Retreat, April 2004, Loon Lake, BC.
UNC-53/NAV2 controls longitudinal migration and interacts with regulators of the actin cytoskeleton.
Molecular Biology and Biochemistry Seminar Series, Simon Fraser University, 2002
En route: The role of Unc-53/NAV in cell guidance
Invited Public Presentations:
Canada Research Chair in Developmental Genetics and Disease Inaugural Lecture: November 8, 2007, Trinity Western University
Of worms and men: What model organisms tell us about human disease.
Graduation Address: Faculty of Natural and Applied Science Graduation Exercises, April 28, 2007 The Garden of Faith
Women in Leadership Luncheon, Langley, BC, June 9, 2006
Of worms and (wo)men: What genetic models tell us about human disease.
St. George’s Anglican Church, August 7, Maple Ridge, BC, 2005
Science and faith: Need they be opposed?
Green Timbers Church, Surrey, BC, November, 2004
Bioethics and the Human Genome Project
Maple Ridge Teachers Association Annual Convention, February 18, 2004, BC.
Building bridges to the world: DNA workshops for Middle and Secondary teachers
Langley and Abbotsford Rotary Clubs, September 2000 and January 2001
Of worms and men: Why studying model systems is important to human disease.
Surrey Chamber of Commerce Lunch for the Mayor, February 21, 2001
Expanding horizons:The role of universities in communities
New Life Church, Abbotsford, November 2000
Facing New Realities: Clones, Chromosomes and Human Genomes
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