~ Faculty - L. Courtney Smith

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L. Courtney Smith
Professor of Biology
Molecular Evolution of the Deuterostome Immune System
Department of Biological Sciences
George Washington University
414 Lisner Hall, 2023 G Street NW
Washington, D.C. 20052

GWU Institute of Biomedical Sciences
Member: Graduate Programs in Genetics and Immunology

Adjunct Appointments:
GWU School of Medicine, Department of Microbiology, Immunology and Tropical Medicine

office: 202-994-9211, fax: 202-994-6100
email: csmith@gwu.edu

B.A. Drake University, Des Moines IA 1974
M.S. University of Minnesota, Minneapolis MN 1976
Ph.D. University of California, Los Angeles CA 1985
Post-Doctoral Work: California Institute of Technology, Pasadena CA

Research Interests:

Our interest in Marine Biomedicine is centered on understanding the innate immune system of the purple sea urchin, Strongylocentrotus purpuratus. Efforts are focused on the functions of the immune cells, or coelomocytes (cells found in the coelom) that become activated in response to infection or injury. We have identified a number of genes that are upregulated in activated coelomocytes in response to lipopolysaccharide (LPS), other pathogen associated molecular patterns, and heat killed Vibrio. These include homologues of the complement cascade and a family of genes called 185/333.

The 185/333 genes are strongly upregulated in response to immune challenge. The messages are unusual because optimal alignments require the insertion of large gaps that define 25 blocks of sequence called elements. The high level of sequence diversity among the messages is primarily based on the presence/absence of elements in addition to small indels and SNPs.

Analysis of the genome suggests that the sea urchin immune system may be much more complex than expected for an invertebrate. A number of large gene families encoding predicted homologues of vertebrate immune proteins were identified. The 185/333 gene family has 50 to 60 members, with many loci clustered tightly together. The genes have two exons; the second exon is composed of mosaic patterns of blocks of sequence called elements that are observed in the messages. In addition to the variable element patterns, the genes also have a variety of repeats that has enabled a second alignment that correlates the elements with the repeats. Surprisingly, both alignments are about equally good. Detailed analysis of the repeat and element sequences strongly suggests that the genes undergo frequent recombination. Comparisons between the sequences of the genes and the message for individual animals have identified a second level of diversification. There is very low sequence identity between genes and messages, suggesting an unknown mechanism for editing the messages either during or after transcription. High rates of diversification of the 185/333 system would be a benefit to the sea urchin because it would be the underlying mechansism to keep pace in the arms race with pathogen diversification.

The 185/333 proteins are expressed in two subsets of the phagocyte class of coelomocytes. The polygonal cells are the largest coelomocytes and when spread have a polygonal shape. They have perinuclear vesicles containing 185/333 proteins. Small phagocytes are perpetually filopodial and do not spread into lamellipodial morphology. They also have 185/333 proteins in cytoplasmic vesicles, but much of the protein is associated with the cell surface and appears on the filopodia in knob-like structures. The number of 185/333-positive coelomocytes increases significantly after immune challenge. In addition to coelomocytes, the major tissues of the sea urchin also have 185/333-positive cells. In particular, the axial organ shows a significant increase in 185/333-positive cells after challenge with LPS.

The close phylogenetic relationship between echinoderms and chordates makes investigations of the sea urchin immune system noteworthy for deducing the evolution of deuterostome immunity. Does the mammalian innate immune system employ diversification mechanisms such as gene recombination and meiotic mispairing like invertebrates and higher plants? Or are these mechanisms not used in mammalian immune response genes because of diversification through somatic rearrangement that is used in the immunoglobulin gene families of the adaptive immune system? What we learn about gene diversification in the sea urchin innate immune system will likely impact how we think about innate immunity in humans and other vertebrates.

Support. This research is funded by the National Science Foundation through 2011.

Selected publications

Dheilly, NM, SV Nair, LC Smith DA Raftos. 2009. Highly variable immune response proteins (185/333) from the sea urchin Strongylocentrotus purpuratus: proteomic analyses indicate diversity within and between individuals. Journal of Immunology, 182:2203-2212.

Buckley, KM, DP Terwilliger, LC Smith. 2008. Sequence variations in 185/333 messages from the purple sea urchin suggest post-transcriptional modifications to increase immune diversity. Journal of Immunology, 181:8585-8594.

Buckley KM, S Munshaw, TB Kepler, LC Smith. 2008. The 185/333 gene family is a rapidly diversifying host-defense gene cluster in the purple sea urchin, Strongylocentrotus purpuratus. Journal of Molecular Biology, 379:912-928.

Brockton V, JH Henson, DA Raftos, AJ Majeske, Y-O Kim, LC Smith. 2008. Localization and diversity of 185/333 proteins from the purple sea urchin, Strongylocentrotus purpuratus (Stimpson); unexpected protein size range and expression in a new coelomocyte type. Journal of Cell Science, 121:339-348.

Buckley KM, LC Smith. 2007. Extraordinary diversity among members of the large gene family, 185/333, from the purple sea urchin, Strongylocentrotus purpuratus. BMC Molecular Biology, 8:68. Available from www.biomedcentral.com/content/pdf/1471-2199-8-68.pdf

Terwilliger, DP, KM Buckley, V Brockton, NJ Ritter, LC Smith. 2007. Distinctive expression patterns of 185/333 genes in the purple sea urchin, Strongylocentrotus purpuratus: an unexpectedly diverse family of transcripts in response to LPS, beta-1,3-glucan, and dsRNA. BMC Molecular Biology, 8:16. Available from www.biomedcentral.com/content/pdf/1471-2199-8-68.pdf

Sodergren et al. (The Sea Urchin Genome Sequencing Consortium) 2006. The genome of the sea urchin Strongylocentrotus purpuratus. Science, 314:941-952.

Rast, JP, LC Smith, M Loza-Coll, T Hibino, GW Litman. 2006. Genomic insights into the immune system of the sea urchin. Science, 314:952-956.

Hibino, T, M Loza-Coll, C Messier, AJ Majeske, AH Cohen, DP Terwilliger, KM Buckley, V Brockton, SV Nair, K Berney, SD Fugmann, MK Anderson, Z Pancer, RA Cameron, LC Smith* & JP Rast*. 2006. The immune gene repertoire encoded in the purple sea urchin genome. Developmental Biology, 300:349-365. (*contributing authors)

Terwilliger, DP, KM Buckley, D Mehta, PG Moorjani, LC Smith. 2006. Unexpected diversity displayed in cDNAs expressed by the immune cells of the purple sea urchin, Strongylocentrotus purpuratus. Physiological Genomics, 26:134-144. Available from http://www.biomedcentral.com/content/pdf/1471-2199-8-16.pdf

Nair, SV, H Del Valle, PS Gross, DP Terwilliger, LC Smith. 2005. Macroarray analysis of coelomocyte gene expression in response to LPS in the sea urchin, Strongylocentrotus purpuratus. Identification of unexpected immune diversity in an invertebrate. Physiological Genomics, 22:33-47. Available from http://physiolgenomics.physiology.org/cgi/reprint/22/1/33

Terwilliger, DP, LA Clow, PS Gross, LC Smith. 2004. Constitutive expression and alternative splicing of the SCR domains of Sp152, the sea urchin homologue of complement factor B. Implications on the evolution of the C2/Bf gene family. Immunogenentics, 56:531-543.

Clow, LA, DA Raftos, PS Gross & LC Smith. 2004. The sea urchin homologue, SpC3, functions as an opsonin. Journal of Experimental Biology, 207:2147-2155.

Multerer, KA, LC Smith. 2004. Two cDNAs from the purple sea urchin, Strongylocentrotus purpuratus, encoding mosaic proteins with domains found in factor H, factor I, and complement components C6 and C7. Immunogenetics, 56:89-106.

Shah, M, KM Brown, LC Smith. 2003. The gene encoding the sea urchin complement protien, SpC3, is expressed in embryos and can be upregulated by bacteria. Developmental and Comparative Immunology, 27:529-538.

Smith, LC. 2002. Thioester function is conserved in SpC3, the sea urchin homologue of the complement component C3. Developmental and Comparative Immunology, 26:603-614.

Gross, PS, LA Clow & LC Smith. 2000. SpC3, the complement homologue from the purple sea urchin, Strongylocentrotus purpuratus, is expressed in two subpopulations of the phagocytic coelomocytes. Immunogenetics, 51:1021-1033.

Clow, LA, PS Gross, C-S Shih, LC Smith. 2000. Expression of SpC3, the sea urchin complement component, in response to lipopolysaccharide. Immunogenetics, 51:1043-1044.

Smith, LC, C-S Shih, SG Dachenhausen. 1998. Coelomocytes specifically express SpBf, a homologue of factor B, the second component in the sea urchin complement system. Journal of Immunology, 161:6784-6793.

Al-Sharif, WZ, JO Sunyer, JD Lambris & LC Smith. 1998. A homologue of the complement component C3 is specifically expressed in sea urchin coelomocytes. Journal of Immunology, 160:2983-2997.

Smith, LC, L Chang, RJ Britten, EH Davidson. 1996. Sea urchin genes expressed in activated coelomocytes are identified by expressed sequence tags (ESTs). Complement homologues and other putative immune response genes suggest immune system homology within the deuterostomes. Journal of Immunology, 156:593-602.

Smith, LC, RJ Britten, EH Davidson. 1995. Lipopolysaccharide activates the sea urchin immune system. Developmental and Comparative Immunology, 19:217-224.

Smith, LC, MG Harrington, RJ Britten, EH Davidson. 1994. The sea urchin profilin gene is expressed in mesenchyme cells during gastrulation. Developmental Biology, 164:463-474.

Smith, LC, RJ Britten, EH Davidson. 1992. SpCoel1, a sea urchin profilin gene expressed specifically in coelomocytes in response to injury. Molecular Biology of the Cell, 3:403-414.


Smith, LC, JP Rast, V Brockton, DP Terwilliger, SV Nair, DM Buckley, AJ Majeske. 2006. The Sea Urchin Immune System. Invertebrate Survival Journal, 3:25-39. Available from www.isj.unimore.it/vol3issue1.htm.

Smith, LC. 2005. Host responses to bacteria: Innate immunity in invertebrates. In: The influence of cooperative bacteria on animal host biology. (MJ McFall-Ngai, B Henderson, EG Ruby, eds.) Advances in Molecular and Cellular Microbiology, 10:293-320. Cambridge University Press.

Smith, LC, LA Clow & DP Terwilliger. 2001. The ancestral complement system in sea urchins. Immunological Reviews, 180:16-34.

Smith, LC. 2001. The complement system in sea urchins. In Phylogenetic Perspectives on the Vertebrate Immune Systems (G Beck, M Sugumaran, E Cooper, eds.). Plenum Publishing Co. pp. 363-372.

Smith, LC, K Azumi, M Nonaka. 1999. Complement systems in invertebrates. The ancient alternative and lectin pathways. Immunopharmacology, 42:107-120.

Gross, PS, WZ Al-Sharif, LA Clow, LC Smith. 1999. Echinoderm immunity and the evolution of the complement system. Developmental and Comparative Immunology, 23:429-442.

Smith, LC, EH Davidson. 1994. The echinoderm immune system: characters shared with the vertebrate immune system, and characters arising later in deuterstome phylogeny. In: Primordial Immunity: Foundations for the Vertebrate Immune System. (G beck, EL Cooper, GS Habicht & JJ Marchalonis, eds.) The New York Academy of Sciences, 712:213-226.

Smith, LC, EH Davidson. 1992. The echinoid immune system and the phylogenetic occurrence of immune mechanisms in deuterostomes. Immunology Today, 13:356-362. The echinoid immune system revisited: reply. Immunology Today, 14:93-94.

For copies of my papers on immune functions in marine sponges, please email me.


BiSc 218 - Innate Immunity (Spring terms)
BiSc 102 - Cell Biology (Fall terms)
BiSc 112 - Immunology (Fall and Spring terms, team taught)

Lab Members:

Katherine Buckley, Post doctoral fellow (kshank@gwu.edu)
Audrey Majeske, Ph.D. Candidate, Biological Sciences (majeskea@gwu.edu)
Chase Miller, M.S. student, Program in Genomics and Bioinformatics (chmille4@gmail.com)
Hyeyoun Chang, PhD Student, Biological Sciences
Julie Ghosh, PhD Student, Biological Sciences
Catherine Schrankel, Undergraduate, Biological Sciences (catsch@gwu.edu)

Other links of interest:
International Society of Developmental and Comparitive Immunology

Last updated on 5-22-08