The Stuart lab studies complex single-celled organisms that cause a staggering amount of human and animal disease worldwide. The research is designed to develop understanding of fundamental molecular and cellular processes in these organisms in order to select approaches for the discovery of new drugs and identify components of these parasites that can be developed into vaccines and diagnostic tools.
The Stuart lab is focused on Trypanosomatid pathogens: Trypanosoma brucei, Trypanosoma cruzi, and Leishmania species. One major focus is on the process of the molecular machinery for and the physiological significance of RNA editing, which is an unusual and essential form of RNA processing that is unique to this group of pathogens. The studies include exploration of the potential for developing drugs directed at this process or its physiological role.
Stuart determined the general mechanism of editing, identified many components of the key complex that performs editing, the editosome, and the functions and interactions of many of these components. He also showed that other complexes collaborate with the editosome in editing and discovered a new multiprotein complex that functions in RNA processing. His lab is exploring editosome functional structure, steps in the editing process, and effects on parasite physiology upon disruption of editing.
A second focus of the Stuart lab is functional genomics. He led the formation of international consortia that completed genome projects that sequenced Trypanosome and Leishmania genomes and interpreted the sequence data. He did this in close collaboration with Peter Myler, Ph.D. [7], and international colleagues. His current projects are building on these sequencing efforts and include the characterization of more than 1,000 proteins in the mitochondrion and determination of their physical and functional associations. This proteomic project is designed to identify and characterize the mitochondrial protein composition, functional organization, and functional pathways for the purpose of discovering the drugs that are needed for the diseases that are caused by this group of pathogens.
A third focus of the Stuart lab is drug discovery. He leads an international consortium that is working together to discover and develop new drugs for trypanosomatid pathogens. The consortium in aggregate has the expertise and facilities that span discovery through Phase 3 clinical trials. Stuart plays a coordinating role and his lab also focuses on identifying, prioritizing and validating potential drug targets in the trypanosomatids. It is developing cell and enzyme based assays that other members of the consortium use in high throughput screens to identify compounds that can provide the foundation for development of new drugs. His lab participates in activities that are designed to identify targets of compounds that are identified by drug screening. This work is conducted in collaboration with Marilyn Parsons [8] and Peter Myler [7].
Much of the support for Stuart’s research is provided by the National Institutes of Health (NIH).
Links:
[1] http://www.seattlebiomed.org/sites/default/files/Stuart_100px.jpg
[2] mailto:ken.stuart@seattlebiomed.org
[3] http://www.seattlebiomed.org/bio/stuart?tab=body
[4] http://www.seattlebiomed.org/bio/stuart?tab=field_bio
[5] http://www.seattlebiomed.org/bio/stuart?tab=publications
[6] http://www.seattlebiomed.org/bio/stuart?tab=field_staff
[7] http://www.seattlebiomed.org/bio/myler
[8] http://www.seattlebiomed.org/bio/parsons
[9] http://www.seattlebiomed.org/22562468
[10] http://www.seattlebiomed.org/22438925
[11] http://www.seattlebiomed.org/22184461
[12] http://www.seattlebiomed.org/22046323
[13] http://www.seattlebiomed.org/21610103
[14] http://www.seattlebiomed.org/publication/fes-cluster-assembly-protein-isd11-essential-trna-thiolation-trypanosoma-brucei
[15] http://www.seattlebiomed.org/publication/high-resolution-crystal-structure-key-editosome-enzyme-trypanosoma-brucei-rna-editing-li
[16] http://www.seattlebiomed.org/publication/protein-protein-interaction-map-trypanosome-20s-editosomes
[17] http://www.seattlebiomed.org/publication/functions-and-cellular-localization-cysteine-desulfurase-and-selenocysteine-lyase-trypan
[18] http://www.seattlebiomed.org/publication/zinc-fingers-krepa3-are-essential-complete-editing-mitochondrial-mrnas-trypanosoma-bruce
[19] http://www.seattlebiomed.org/publication/f0f1-atp-synthase-complex-contains-novel-subunits-and-essential-procyclic-trypanosoma-br
[20] http://www.seattlebiomed.org/publication/differential-functions-two-editosome-exouases-trypanosoma-brucei
[21] http://www.seattlebiomed.org/publication/mrb1-complex-functions-kinetoplastid-rna-processing
[22] http://www.seattlebiomed.org/publication/comprehensive-analysis-trypanosoma-brucei-mitochondrial-proteome
[23] http://www.seattlebiomed.org/publication/protein-composition-trypanosoma-brucei-mitochondrial-membranes
[24] http://www.seattlebiomed.org/publication/structural-and-functional-association-trypanosoma-brucei-mix-protein-cytochrome-c-oxidas
[25] http://www.seattlebiomed.org/publication/krepa3-zinc-finger-motifs-and-ob-fold-domain-are-essential-rna-editing-and-survival-tryp
[26] http://www.seattlebiomed.org/publication/discovery-drug-inhibitors-essential-rna-editing-ligase-trypanosoma-brucei
[27] http://www.seattlebiomed.org/publication/determinants-association-and-guide-rna-directed-endonuclease-cleavage-purified-rna-editi
[28] http://www.seattlebiomed.org/publication/trypanosoma-brucei-mitochondrial-ribosomes-affinity-purification-and-component-identific
[29] http://www.seattlebiomed.org/publication/krepa6-rna-binding-protein-essential-editosome-integrity-and-survival-trypanosoma-brucei
[30] http://www.seattlebiomed.org/publication/structure-and-function-native-and-recombinant-mitochondrial-mrp1mrp2-complex-trypanosoma
[31] http://www.seattlebiomed.org/publication/tbrgg1-essential-protein-involved-kinetoplastid-rna-metabolism-associated-novel-multipro
[32] http://www.seattlebiomed.org/publication/kinetoplastids-related-protozoan-pathogens-different-diseases
[33] http://www.seattlebiomed.org/publication/mitochondrial-complexes-trypanosoma-brucei-novel-complex-and-unique-oxidoreductase-compl
[34] http://www.seattlebiomed.org/publication/rna-editing-trypanosoma-brucei-requires-three-different-editosomes
[35] http://www.seattlebiomed.org/publication/isolation-and-compositional-analysis-trypanosomatid-editosomes
[36] http://www.seattlebiomed.org/publication/uridine-insertiondeletion-editing-activities
[37] http://www.seattlebiomed.org/publication/essential-role-krepb4-rna-editing-and-structural-integrity-editosome-trypanosoma-brucei
[38] http://www.seattlebiomed.org/publication/role-biopterin-transporter-bt1-gene-growth-and-infectivity-of%C2%A0-leishmania
[39] http://www.seattlebiomed.org/publication/creation-tetracycline-regulatable-knockouts-orff-gene-ld1-locus-leishmania-donovani
[40] http://www.seattlebiomed.org/publication/compositionally-and-functionally-distinct-editosomes-trypanosoma-brucei-0
[41] http://www.seattlebiomed.org/publication/krepa4-rna-binding-protein-essential-editosome-integrity-and-survival-trypanosoma-brucei
[42] http://www.seattlebiomed.org/publication/structural-basis-utp-specificity-rna-editing-tutases-trypanosoma-brucei
[43] http://www.seattlebiomed.org/publication/f1-atp-synthase-complex-bloodstream-stage-trypanosomes-has-unusual-and-essential-functio
[44] http://www.seattlebiomed.org/publication/essential-rnase-iii-insertion-editing-endonuclease-trypanosoma-brucei
[45] http://www.seattlebiomed.org/publication/deletion-site-editing-endonuclease-trypanosoma-brucei
[46] http://www.seattlebiomed.org/publication/essential-rnase-iii-insertion-editing-endonuclease-trypanosoma-brucei-0
[47] http://www.seattlebiomed.org/publication/comparative-genomics-trypanosomatid-parasitic-protozoa-0
[48] http://www.seattlebiomed.org/publication/genome-kinetoplastid-parasite-leishmania-major
[49] http://www.seattlebiomed.org/publication/genome-sequence-trypanosoma-cruzi-etiologic-agent-chagas-disease
[50] http://www.seattlebiomed.org/publication/ploidy-changes-associated-disruption-two-adjacent-genes-leishmania-major-chromosome-1
[51] http://www.seattlebiomed.org/publication/tbmp42-protein-component-rna-editing-complex-african-trypanosomes-has-endo-exoribonuclea
[52] http://www.seattlebiomed.org/publication/complex-management-rna-editing-trypanosomes
[53] http://www.seattlebiomed.org/publication/rna-interference-analyses-suggest-transcript-specific-regulatory-role-mitochondrial-rna-
[54] http://www.seattlebiomed.org/publication/14-3-3-proteins-trypanosoma-brucei-function-motility-cytokinesis-and-cell-cycle
[55] http://www.seattlebiomed.org/publication/transcription-initiation-and-termination-leishmania-major-chromosome-3
[56] http://www.seattlebiomed.org/publication/gene-synteny-and-evolution-genome-architecture-trypanosomatids
[57] http://www.seattlebiomed.org/publication/genomic-organization-and-gene-expression-chromosomal-region-leishmania-major
[58] http://www.seattlebiomed.org/publication/vitro-assays-kinetoplastid-u-insertion-deletion-editing-and-associated-activities
[59] http://www.seattlebiomed.org/publication/identification-and-characterization-trypanosome-rna-editing-complex-components
[60] http://www.seattlebiomed.org/publication/shotgun-optical-mapping-entire-leishmania-major-friedlin-genome
[61] http://www.seattlebiomed.org/publication/comparative-analysis-editosome-proteins-trypanosomatids
[62] http://www.seattlebiomed.org/publication/separate-insertion-and-deletion-subcomplexes-trypanosoma-brucei-rna-editing-complex
[63] http://www.seattlebiomed.org/publication/leishmania-major-chromosome-3-contains-two-long-convergent-polycistronic-gene-clusters-s
[64] http://www.seattlebiomed.org/publication/mass-spectrometric-analysis-editosome-and-other-multiprotein-complexes-trypanosoma-bruce
[65] http://www.seattlebiomed.org/publication/dyskinetoplastic-trypanosoma-brucei-contains-functional-editing-complexes
[66] http://www.seattlebiomed.org/publication/tbmp57-3-terminal-uridylyl-transferase-tutase-trypanosoma-brucei-editosome
[67] http://www.seattlebiomed.org/publication/evaluation-differential-gene-expression-leishmania-major-friedlin-procyclics-and-metacyc
[68] http://www.seattlebiomed.org/publication/tbmp44-essential-rna-editing-and-structural-integrity-editosome-trypanosoma-brucei
[69] http://www.seattlebiomed.org/publication/transcription-leishmania-major-friedlin-chromosome-1-initiates-both-directions-within-si
[70] http://www.seattlebiomed.org/publication/identification-novel-components-trypanosoma-brucei-editosomes
[71] http://www.seattlebiomed.org/publication/kinetoplastid-rna-editing-ligases-complex-association-characterization-and-substrate-req
[72] http://www.seattlebiomed.org/publication/novel-active-dna-topoisomerase-i-leishmania-donovani
[73] http://www.seattlebiomed.org/publication/rna-editing-complexity-and-complications
[74] http://www.seattlebiomed.org/publication/natural-and-induced-dyskinetoplastic-trypanosomatids-how-live-without-mitochondrial-dna
[75] http://www.seattlebiomed.org/publication/tbmp81-required-rna-editing-trypanosoma-brucei
[76] http://www.seattlebiomed.org/publication/endoribonuclease-activities-trypanosoma-brucei-mitochondria
[77] http://www.seattlebiomed.org/publication/rna-sequence-and-base-pairing-effects-insertion-editing-trypanosoma-brucei
[78] http://www.seattlebiomed.org/publication/role-uridylate-specific-exoribonuclease-activity-trypanosoma-brucei-rna-editing
[79] http://www.seattlebiomed.org/publication/low-background-inducible-promoter-system-leishmania-donovani
[80] http://www.seattlebiomed.org/publication/expression-biopterin-transporter-bt1-protein-leishmania
[81] http://www.seattlebiomed.org/publication/composition-editing-complex-trypanosoma-brucei
[82] http://www.seattlebiomed.org/publication/specificity-nucleotide-removal-during-rna-editing-trypanosoma-brucei
[83] http://www.seattlebiomed.org/publication/leishmania-genome-project-new-insights-gene-organization-and-function
[84] http://www.seattlebiomed.org/publication/four-related-proteins-trypanosoma-brucei-rna-editing-complex
[85] http://www.seattlebiomed.org/publication/genomic-organization-and-functional-characterization-leishmania-major-friedlin-ribosomal
[86] http://www.seattlebiomed.org/publication/mitochondrial-ribonuclease-p-activity-trypanosoma-brucei
[87] http://www.seattlebiomed.org/publication/conservation-ld1-region-leishmania-includes-dna-implicated-ld1-amplification
[88] http://www.seattlebiomed.org/publication/rna-ligase-essential-rna-editing-and-survival-bloodstream-form-trypanosoma-brucei
[89] http://www.seattlebiomed.org/publication/association-two-novel-proteins-tbmp52-and-tbmp48-trypanosoma-brucei-rna-editing-complex
[90] http://www.seattlebiomed.org/publication/tetracycline-regulated-gene-expression-leishmania-donovani
[91] http://www.seattlebiomed.org/publication/uridylate-addition-and-rna-ligation-contribute-specificity-kinetoplastid-insertion-rna-e
[92] http://www.seattlebiomed.org/publication/sequence-bias-edited-kinetoplastid-rnas
[93] http://www.seattlebiomed.org/publication/immunization-recombinant-ld1-antigens-protects-against-experimental-leishmaniasis
[94] http://www.seattlebiomed.org/publication/genomic-organization-and-gene-function-leishmania
[95] http://www.seattlebiomed.org/publication/recent-developments-leishmania-genome-project
[96] http://www.seattlebiomed.org/publication/unusual-gene-organization-leishmania-major-chromosome-1-may-reflect-novel-transcription-
[97] http://www.seattlebiomed.org/publication/size-difference-between-leishmania-major-friedlin-chromosome-one-homologues-localized-su
[98] http://www.seattlebiomed.org/publication/phylogenetic-analysis-5-subterminal-region-isolates-leishmania-rna-virus-1
[99] http://www.seattlebiomed.org/publication/leishmania-donovani-characterization-and-expression-orff-gene-amplified-ldi-locus
[100] http://www.seattlebiomed.org/publication/characterization-leishmania-donovani-ribosomal-rna-promoter
[101] http://www.seattlebiomed.org/publication/leishmania-donovani-ld1-locus-gene-orfg-encodes-biopterin-transporter-bt1
[102] http://www.seattlebiomed.org/publication/serodiagnosis-leishmaniasis-recombinant-orff-antigen
[103] http://www.seattlebiomed.org/publication/kinetoplastid-rna-editing-does-not-require-terminal-3-hydroxyl-guide-rna-modifications-g
[104] http://www.seattlebiomed.org/publication/leishmania-major-friedlin-chromosome-1-has-unusual-distribution-protein-coding-genes
[105] http://www.seattlebiomed.org/publication/protein-farnesyltransferase-trypanosoma-brucei-heterodimer-61-and-65-kda-subunits-new-ta
[106] http://www.seattlebiomed.org/publication/association-guide-rna-binding-protein-gbp21-active-rna-editing-complexes-trypanosoma-bru
[107] http://www.seattlebiomed.org/publication/investigating-mechanism-and-machinery-rna-editing
[108] http://www.seattlebiomed.org/publication/kinetoplastid-rna-editing-complexes-and-catalysts
[109] http://www.seattlebiomed.org/publication/prenylation-proteins-trypanosoma-brucei
[110] http://www.seattlebiomed.org/publication/rna-editing-getting-u-rna
[111] http://www.seattlebiomed.org/publication/rna-editing-kinetoplastid-protozoa
[112] http://www.seattlebiomed.org/publication/rna-editing-mechanism-grna-specified-uridylate-insertion-precursor-mrna
[113] http://www.seattlebiomed.org/publication/complexes-trypanosoma-brucei-exhibit-deletion-editing-and-other-editing-associated-prope
[114] http://www.seattlebiomed.org/publication/direct-visualization-uridylate-deletion-vitro-suggests-mechanism-kinetoplastid-rna-editi
[115] http://www.seattlebiomed.org/publication/increased-expression-ld1-genes-transcribed-rna-polymerase-i-leishmania-donovani-result-d
[116] http://www.seattlebiomed.org/publication/intracellular-localization-lrv1-infected-leishmania-cells-and-epitope-conservation-coat-
[117] http://www.seattlebiomed.org/publication/long-range-restriction-mapping-megabase-sized-chromosomes-may-be-homologs-trypanosoma-br
[118] http://www.seattlebiomed.org/publication/quantitation-rna-editing-substrates-products-and-potential-intermediates-implications-de
[119] http://www.seattlebiomed.org/publication/developmental-regulation-rna-editing-and-polyadenylation-four-life-cycle-stages-trypanos
[120] http://www.seattlebiomed.org/publication/frequently-amplified-region-leishmania-contains-gene-conserved-prokaryotes-and-eukaryote
[121] http://www.seattlebiomed.org/publication/amplified-dna-element-leishmania-encodes-potential-integral-membrane-and-nucleotide-bind
[122] http://www.seattlebiomed.org/publication/mitochondrial-transcripts-are-processed-are-not-edited-normally-trypanosoma-equiperdum-a
[123] http://www.seattlebiomed.org/publication/editing-trypanosoma-brucei-maxicircle-cr5-mrna-generates-variable-carboxy-terminal-predi
[124] http://www.seattlebiomed.org/publication/assembly-mitochondrial-ribonucleoprotein-complexes-involves-specific-guide-rna-grna-bind
[125] http://www.seattlebiomed.org/publication/trypanosoma-brucei-mitochondrial-cr4-gene-encodes-extensively-edited-mrna-completely-edi
[126] http://www.seattlebiomed.org/publication/multiple-guide-rnas-identical-editing-trypanosoma-brucei-apocytochrome-b-mrna-have-unusu
[127] http://www.seattlebiomed.org/publication/early-expression-trypanosoma-brucei-vsg-gene-duplicated-incomplete-basic-copy
[128] http://www.seattlebiomed.org/publication/alkane-inducible-candida-maltosa-ali1-gene-product-nadhubiquinone-oxidoreductase-subunit
[129] http://www.seattlebiomed.org/publication/nucleotide-sequence-minicircle-leishmania-infantum
[130] http://www.seattlebiomed.org/publication/extensive-editing-cr2-maxicircle-transcripts-trypanosoma-brucei-predicts-protein-homolog
[131] http://www.seattlebiomed.org/publication/ld1-amplified-element-leishmania-infantum-encodes-homolog-ribosomal-protein-l37
[132] http://www.seattlebiomed.org/publication/expression-retroposon-sequence-upstream-putative-trypanosoma-brucei-variant-surface-glyc
[133] http://www.seattlebiomed.org/publication/trypanosoma-brucei-minicircles-encode-multiple-guide-rnas-which-can-direct-editing-exten
[134] http://www.seattlebiomed.org/publication/rna-editing-process-trypanosoma-brucei
[135] http://www.seattlebiomed.org/publication/conservation-grna-gene-cassette-structure-african-trypanosomes-despite-divergence-defini
[136] http://www.seattlebiomed.org/publication/sequences-three-trypanosoma-congolense-maxicircle-genes-allow-prediction-regions-encodin
[137] http://www.seattlebiomed.org/publication/maxicircle-dna-and-edited-mrna-sequences-closely-related-trypanosome-species-implication
[138] http://www.seattlebiomed.org/publication/trypanosoma-brucei-minicircle-encodes-same-grnas-do-minicircles-tequiperdum-atcc-30019-a
[139] http://www.seattlebiomed.org/publication/structural-organization-maxicircle-variable-region-trypanosoma-brucei-identification-pot
[140] http://www.seattlebiomed.org/publication/multicopy-extrachromosomal-dna-leishmania-infantum-contains-two-inverted-repeats-275-kil
[141] http://www.seattlebiomed.org/publication/molecular-organization-leishmania-rna-virus-1
[142] http://www.seattlebiomed.org/publication/distribution-and-sequence-divergence-lrv1-viruses-among-different-leishmania-species
[143] http://www.seattlebiomed.org/publication/transcribing-and-replicating-particles-double-stranded-rna-virus-leishmania
[144] http://www.seattlebiomed.org/publication/transcript-specific-developmental-regulation-polyadenylation-trypanosoma-brucei-mitochon
[145] http://www.seattlebiomed.org/publication/maxicircle-cr1-transcripts-trypanosoma-brucei-are-edited-and-developmentally-regulated-a
[146] http://www.seattlebiomed.org/publication/chimeric-and-truncated-rnas-trypanosoma-brucei-suggest-transesterifications-non-consecut
[147] http://www.seattlebiomed.org/publication/guide-rnas-transcripts-developmentally-regulated-rna-editing-are-present-both-life-cycle
[148] http://www.seattlebiomed.org/publication/vitro-guide-rnamrna-chimaera-formation-trypanosoma-brucei-rna-editing
[149] http://www.seattlebiomed.org/publication/lrv1-viral-particles-leishmania-guyanensis-contain-double-stranded-or-single-stranded-rn
[150] http://www.seattlebiomed.org/publication/mitochondrial-dna-kinetoplastids
[151] http://www.seattlebiomed.org/publication/mitochondrial-dna-kinetoplastids-0
[152] http://www.seattlebiomed.org/publication/extensive-editing-both-processed-and-preprocessed-maxicircle-cr6-transcripts-trypanosoma
[153] http://www.seattlebiomed.org/publication/cycles-progressive-realignment-grna-mrna-rna-editing
[154] http://www.seattlebiomed.org/publication/rna-editing-kinetoplastid-protozoa-0
[155] http://www.seattlebiomed.org/publication/two-atpase-6-mrnas-leishmania-tarentolae-differ-their-3-ends
[156] http://www.seattlebiomed.org/publication/dna-sequence-ld1-which-occurs-several-genomic-organizations-leishmania
[157] http://www.seattlebiomed.org/publication/circular-and-linear-multicopy-dnas-leishmania
[158] http://www.seattlebiomed.org/publication/trypanosoma-brucei-analysis-codon-usage-and-nucleotide-composition-nuclear-genes
[159] http://www.seattlebiomed.org/publication/rna-editing-mitochondrial-mrna-trypanosomatids
[160] http://www.seattlebiomed.org/publication/rna-editing-trypanosomatid-mitochondria
[161] http://www.seattlebiomed.org/publication/simple-method-cloning-blunt-ended-dna-fragments
[162] http://www.seattlebiomed.org/publication/trypanosome-leucine-repeat-gene-variant-surface-glycoprotein-expression-site-encodes-put
[163] http://www.seattlebiomed.org/publication/murf3-gene-t-brucei-contains-multiple-domains-extensive-editing-and-homologous-subunit-n
[164] http://www.seattlebiomed.org/publication/retroposon-5-flank-trypanosoma-brucei-vsg-gene-lacks-insertional-terminal-repeats
[165] http://www.seattlebiomed.org/publication/extensively-edited-mitochondrial-transcript-kinetoplastids-encodes-protein-homologous-at
[166] http://www.seattlebiomed.org/publication/rna-editing-creation-nucleotide-sequences-mrna-minireview
[167] http://www.seattlebiomed.org/publication/novel-telomeric-gene-conversion-trypanosoma-brucei
[168] http://www.seattlebiomed.org/publication/trypanosomatids-mitochondrial-rna-editing
[169] http://www.seattlebiomed.org/publication/rna-editing-new-insights-storage-and-expression-genetic-information
[170] http://www.seattlebiomed.org/publication/trypanosoma-brucei-conserved-sequence-organization-3-telomeric-variant-surface-glycoprot
[171] http://www.seattlebiomed.org/publication/transcripts-co-transposed-segment-variant-surface-glycoprotein-genes-are-trypanosoma-bru
[172] http://www.seattlebiomed.org/publication/trypanosoma-brucei-frequent-loss-telomeric-variant-surface-glycoprotein-gene
[173] http://www.seattlebiomed.org/publication/lr1-candidate-rna-virus-leishmania
[174] http://www.seattlebiomed.org/publication/characterization-cytochrome-c-oxidase-iii-transcripts-are-edited-only-3-region
[175] http://www.seattlebiomed.org/publication/changes-telomere-length-associated-antigenic-variation-trypanosoma-brucei
[176] http://www.seattlebiomed.org/publication/multiple-events-associated-antigenic-switching-trypanosoma-brucei
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