Elodie Ghedin
Elodie Ghedin
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Professor of Epidemiology
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Professional overview
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A molecular parasitologist and virologist, Dr. Elodie Ghedin uses genomics tools to explore host-pathogen interactions in filarial worms (which cause River Blindness and Lymphatic Filariasis) and in viral infections. Her laboratory also explores influenza virus diversity in the infected host and the respiratory tract microbiome to understand transmission dynamics.
Dr. Ghedin’s omics-based predictive modeling project aims to predict severe disease outcome of influenza to develop point of care testing, as some people are more prone to severe versus mild influenza infections. Additionally, her Zika research will be used to develop predictive models for Zika disease severity.
In the Ghedin Lab, Dr. Ghedin offers students an opportunity to study genomic characteristics of human parasites and other pathogens. The research is multidisciplinary and draws upon the tools of genomics, molecular virology, and computational biology. Some projects include the study of influenza virus evolution and emergence, the analysis of the microbiome and mycobiome (fungal microbiota) associated with the pathogenesis of lung obstruction and emphysema in HIV patients, and the characterization of endosymbiotic interactions between filarial worms and Wolbachia. Additionally, Dr. Ghedin also collaborates on the GoViral Project.
As biology and diseases are all interrelated, in her Essentials of Public Health Biology class, Dr. Ghedin teaches the importance of having a foundation in human biology in order to work in any area of public health.
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Education
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BS, Biology, McGill University, Montreal, CanadaMS, Environmental Sciences, University of Quebec, Montreal, CanadaPhD, Molecular Parasitology, McGill University, Montreal, Canada
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Honors and awards
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American Academy of Microbiology Fellow (2017)Kavli Frontiers of Science Fellow (2012)MacArthur Fellow (2011)Chancellor’s Distinguished Research Award (2010)
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Areas of research and study
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BiologyGenomicsInfectious DiseasesViral Infections
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Publications
Publications
LdARF1 in trafficking and structural maintenance of the trans-Golgi cisternal network in the protozoan pathogen Leishmania donovani
AbstractPorter-Kelley, J. M., Gerald, N. J., Engel, J. C., Ghedin, E., & Dwyer, D. M. (n.d.).Publication year
2004Journal title
TrafficVolume
5Issue
11Page(s)
868-883AbstractAdenosine diphosphate ribosylation factors (ARFs) are small guanosine-5′-triphosphatases that are essential in vesicular trafficking and in the maintenance of the Golgi network. In this report, we identified a homolog of the mammalian ARF1 in the human pathogenic protozoan parasite, Leishmania donovani (Ld). Ld ARF1 is a 549 bp gene encoding a 183-amino acid deduced protein of ∼20 kDa. We demonstrated by Southern blot analysis that there are at least two copies of ARF1 in the Ld genome. Moreover, Northern blot analysis revealed that Ld ARF1 is expressed on a 1.35 kb transcript in both the insect vector (promastigotes) and mammalian host (amastigotes) forms of this parasite. Fluorescent microscopy studies using Ld promastigotes episomally transfected with an ARFI::GFP (green fluorescent protein) chimeric construct showed that such chimeras appeared to localize to the Golgi region of these organisms. This observation was verified by immunoelectron microscopy using an anti-GFP antibody. Such studies also revealed that Ld ARF1::GFP chimeras localized to trans-Golgi vesicles, the flagellar pocket/reservoir and other vesicles located between the trans-Golgi network and flagellar pocket in these apically polarized cells. Fluorescence recovery after photobleaching and fluorescence loss in photobleaching experiments revealed both the dynamic binding and releasing activity of Ld ARF1 from the Golgi network in these parasites. Further, episomal expression of a constitutively active ("on") ARF1 (Q71L mutation) resulted in the aberrant swelling and distended-structure of the trans-Golgi cisternae in these cells. These results show that Ld ARF1 is transiently associated with the Golgi network and plays a role in the structural maintenance of this organelle in these important human pathogens.Mechanisms of HTLV-1 transformation.
AbstractKehn, K., Berro, R., De La Fuente, C., Strouss, K., Ghedin, E., Dadgar, S., Bottazzi, M. E., Pumfery, A., & Kashanchi, F. (n.d.).Publication year
2004Journal title
Frontiers in bioscience : a journal and virtual libraryVolume
9Page(s)
2347-2372AbstractHTLV-1 is the etiological agent of the fatal disease adult T-cell leukemia. The virus encodes many proteins including several accessory proteins, p12I, p13II, p27I, and p30II, whose roles have recently begun to be elucidated. These accessory proteins are important in T-cell activation, transcriptional regulation, viral persistence, and virus assembly. The viral oncogene Tax is thought to be largely responsible for tumorigenesis, although the precise mechanisms underlying transformation are not completely understood. Tax has a profound impact on transcription, cell growth regulation, genomic stability and apoptosis. This review will provide possible contributions of the accessory proteins to transformation as well as highlight the alterations of the above-mentioned cellular events by Tax. Animal models of both Tax and the accessory proteins are also included based on the essential information on the transformation process in vivo that they provide.Role of viral regulatory and accessory proteins in HIV-1 replication.
AbstractSeelamgari, A., Maddukuri, A., Berro, R., De La Fuente, C., Kehn, K., Deng, L., Dadgar, S., Bottazzi, M. E., Ghedin, E., Pumfery, A., & Kashanchi, F. (n.d.).Publication year
2004Journal title
Frontiers in bioscience : a journal and virtual libraryVolume
9Page(s)
2388-2413AbstractHuman immunodeficiency virus-1 (HIV-1) is the causative agent of acquired immune deficiency syndrome (AIDS), a disease characterized by CD4+ T lymphocyte depletion. HIV-1 replicates actively in a variety of cells by encoding several regulatory (Tat and Rev) and accessory (Vpr, Vif, Vpu, and Nef) proteins. Accessory proteins, thought initially to be dispensable for infection, have now been shown to be important for efficient infection in vivo. Recent evidence suggests that certain viral proteins, like Vif, have evolved to overcome the antiviral mechanisms of the host, while proteins like Nef, which are markers for disease pathogenesis in vivo, help to increase pathogenesis by targeting bystander cells. Thus, these proteins control many aspects of the virus life cycle as well as host cell function, namely gene regulation and apoptosis. Understanding the mechanisms by which the virus is able to successfully replicate in host cells and subsequently cause gradual destruction of the immune system may yield new approaches for therapeutic strategies. In this review, we attempt to integrate information on the role of these regulatory and accessory proteins, emphasizing their interactions with other viral and cellular components, and the subsequent effect on viral replication.The ingi and RIME non-LTR Retrotransposons are Not Randomly Distributed in the Genome of Trypanosoma brucei
AbstractBringaud, F., Biteau, N., Zuiderwijk, E., Berriman, M., El-Sayed, N. M., Ghedin, E., Melville, S. E., Hall, N., & Baltz, T. (n.d.).Publication year
2004Journal title
Molecular Biology and EvolutionVolume
21Issue
3Page(s)
520-528AbstractThe ingi (long and autonomous) and RIME (short and nonautonomous) non-long-terminal repeat retrotransposons are the most abundant mobile elements characterized to date in the genome of the African trypanosome Trypanosoma brucei. These retrotransposons were thought to be randomly distributed, but a detailed and comprehensive analysis of their genomic distribution had not been performed until now. To address this question, we analyzed the ingi/RIME sequences and flanking sequences from the ongoing T. brucei genome sequencing project (TREU927/4 strain). Among the 81 ingi/ RIME elements analyzed, 60% are complete, and 7% of the ingi elements (approximately 15 copies per haploid genome) appear to encode for their own transposition. The size of the direct repeat flanking the ingi/RIME retrotransposons is conserved (i.e., 12-bp), and a strong 11-bp consensus pattern precedes the 5′-direct repeat. The presence of a consensus pattern upstream of the retroelements was confirmed by the analysis of the base occurrence in 294 GSS containing 5′-adjacent ingi/RIME sequences. The conserved sequence is present upstream of ingis and RIMEs, suggesting that ingi-encoded enzymatic activities are used for retrotransposition of RIMEs, which are short nonautonomous retroelements. In conclusion, the ingi and RIME retroelements are not randomly distributed in the genome of T. brucei and are preceded by a conserved sequence, which may be the recognition site of the ingi-encoded endonuclease.Use of multi-virus array for the study of human viral and retroviral pathogens: Gene expression studies ChIP-chip analysis
AbstractGhedin, E., Pumfery, A., De La Fuente, C., Yao, K., Miller, N., Lacoste, V., Quackenbush, J., Jacobson, S., & Kashanchi, F. (n.d.).Publication year
2004Journal title
RetrovirologyVolume
1AbstractBackground. Since the discovery of human immunodeficiency virus (HIV-1) twenty years ago, AIDS has become one of the most studied diseases. A number of viruses have subsequently been identified to contribute to the pathogenesis of HIV and its opportunistic infections and cancers. Therefore, a multi-virus array containing eight human viruses implicated in AIDS pathogenesis was developed and its efficacy in various applications was characterized. Results. The amplified open reading frames (ORFs) of human immunodeficiency virus type 1, human T cell leukemia virus types 1 and 2, hepatitis C virus, Epstein-Barr virus, human herpesvirus 6A and 6B, and Kaposi's sarcoma-associated herpesvirus were spotted on glass slides and hybridized to DNA and RNA samples. Using a random priming method for labeling genomic DNA or cDNA probes, we show specific detection of genomic viral DNA from cells infected with the human herpesviruses, and effectively demonstrate the inhibitory effects of a cellular cyclin dependent kinase inhibitor on viral gene expression in HIV-1 and KSHV latently infected cells. In addition, we coupled chromatin immunoprecipitation with the virus chip (ChIP-chip) to study cellular protein and DNA binding. Conclusions. An amplicon based virus chip representing eight human viruses was successfully used to identify each virus with little cross hybridization. Furthermore, the identity of both viruses was correctly determined in co-infected cells. The utility of the virus chip was demonstrated by a variety of expression studies. Additionally, this is the first demonstrated use of ChIP-chip analysis to show specific binding of proteins to viral DNA, which, importantly, did not require further amplification for detection.The sequence and analysis of Trypanosoma brucei chromosome II
AbstractEl-Sayed, N. M. A., Ghedin, E., Song, J., MacLeod, A., Bringaud, F., Larkin, C., Wanless, D., Peterson, J., Hou, L., Taylor, S., Tweedie, A., Biteau, N., Khalak, H. G., Lin, X., Mason, T., Hannick, L., Caler, E., Blandin, G., Bartholomeu, D., … Donelson, J. E. (n.d.).Publication year
2003Journal title
Nucleic acids researchVolume
31Issue
16Page(s)
4856-4863AbstractWe report here the sequence of chromosome II from Trypenosoma brucei, the causative agent of African sleeping sickness. The 1.2-Mb pairs encode about 470 predicted genes organised in 17 directional clusters on either strand, the largest cluster of which has 92 genes lined up over a 284-kb region. An analysis of the GC skew reveals strand compositional asymmetries that coincide with the distribution of protein-coding genes, suggesting these asymmetries may be the result of transcription-coupled repair on coding versus non-coding strand. A 5-cM genetic map of the chromosome reveals recombinational 'hot' and 'cold' regions, the latter of which is predicted to include the putative centromere. One end of the chromosome consists of a 250-kb region almost exclusively composed of RHS (pseudo)genes that belong to a newly characterised multigene family containing a hot spot of insertion for retroelements. Interspersed with the RHS genes are a few copies of truncated RNA polymerase pseudogenes as well as expression site associated (pseudo)genes (ESAGs) 3 and 4, and 76 bp repeats. These features are reminiscent of a vestigial variant surface glycoprotein (VSG) gene expression site. The other end of the chromosome contains a 30-kb array of VSG genes, the majority of which are pseudogenes, suggesting that this region may be a site for modular de novo construction of VSG gene diversity during transposition/gene conversion events.Identification of non-autonomous non-LTR retrotransposons in the genome of Trypanosoma cruzi
AbstractBringaud, F., García-Pérez, J. L., Heras, S. R., Ghedin, E., El-Sayed, N. M., Andersson, B., Baltz, T., & Lopez, M. C. (n.d.).Publication year
2002Journal title
Molecular and Biochemical ParasitologyVolume
124Issue
1Page(s)
73-78AbstractAs observed for most eukaryotic cells, trypanosomatids contains non-LTR retrotransposons randomly inserted in the nuclear genome. Autonomous retroelements which, code for their own transposition, have been characterized in Trypanosoma brucei (ingi) and Trypanosoma cruzi (L1Tc), whereas non-autonomous retroelements have only been characterized in T. brucei (RIME). Here, we have characterized in the genome of Trypanosoma cruzi four complete copies of a non-autonomous non-LTR retrotransposon, called NARTc. This 0.26 kb NARTc element has the characteristics of non-LTR retrotransposons: the presence a poly(dA) tail and of a short flanking duplicated motif. Analysis of the Genome Survey Sequence databases indicated that the Trypanosoma cruzi haploid genome contains about 140 NARTc copies and about twice as many L1Tc copies. Interestingly, the NARTc and L1Tc retroelements share, with the Trypanosoma brucei ingi and RIME retrotransposons, a common sequence (the first 45 bp with 91% identity), whereas the remaining sequences are very divergent. This suggests that these four trypanosome non-LTR retrotransposons were derived from the same common ancester and the sequence of their 5'-extremity may have a functional role. In addition, the genome of Leishmania major contains the same conserved motif present in the trypanosome retroelements, whicle no transposable elements have been detected so far in Leishmania sp.Molecular dissection of the functional domains of a unique, tartrate-resistant, surface membrane acid phosphatase in the primitive human pathogen Leishmania donovani
AbstractShakarian, A. M., Joshi, M. B., Ghedin, E., & Dwyer, D. M. (n.d.).Publication year
2002Journal title
Journal of Biological ChemistryVolume
277Issue
20Page(s)
17994-18001AbstractThe primitive trypanosomatid pathogen of humans, Leishmania donovani, constitutively expresses a unique externally oriented, tartrate-resistant, acid phosphatase on its surface membrane. This is of interest because these organisms are obligate intracellular protozoan parasites that reside and multiply within the hydrolytic milieu of mammalian macrophage phago-lysosomes. Here we report the identification of the gene encoding this novel L. donovani enzyme. In addition, we characterized its structure, demonstrated its constitutive expression in both parasite developmental forms, and determined the cell surface membrane localization of its translated protein product. Further, we used a variety of green fluorescent protein chimeric constructs as reporters in a homologous leishmanial expression system to dissect the functional domains of this unique, tartrate-resistant, surface membrane enzyme.Secretory and endocytic pathways converge in a dynamic endosomal system in a primitive protozoan
AbstractGhedin, E., Debrabant, A., Engel, J. C., & Dwyer, D. M. (n.d.).Publication year
2001Journal title
TrafficVolume
2Issue
3Page(s)
175-188AbstractLeishmania are a group of primitive eukaryotic trypanosomatid protozoa that are apically polarized with a flagellum at their anterior end. Surrounding the base of the flagellum is the flagellar reservoir that constitutes the site for endocytosis and exocytosis in these organisms. In the present study, we define a novel multivesicular tubular compartment involved in the intracellular trafficking of macromolecules in Leishmania. This dynamic structure appears to subtend the flagellar reservoir and extends towards the posterior end of the cell. Functional domains of several surface-expressed proteins, such as the gp63 glycosyl phosphatidyl inositol anchor and the 3′nucleotidase/nuclease transmembrane domain were fused to green fluorescent protein. These chimeric proteins were found to traffic through the secretory pathway and, while reaching their intended destinations, also accumulated within the intracellular tubular compartment. Using various compounds that are efficient fluid-phase markers used to track endocytosis in higher eukaryotes, we showed that this tubular compartment constitutes an important station in the endocytic pathway of these cells. Based on our functional observations of its role in the trafficking of expressed proteins and endocytosed markers, this compartment appears to have properties similar to endosomes of higher eukaryotes.Dissection of the functional domains of the Leishmania surface membrane 3'-nucleotidase/nuclease, a unique member of the class I nuclease family
AbstractDebrabant, A., Ghedin, E., & Dwyer, D. M. (n.d.).Publication year
2000Journal title
Journal of Biological ChemistryVolume
275Issue
21Page(s)
16366-16372AbstractClass I nucleases are a family of enzymes that specifically hydrolyze single-stranded nucleic acids. Recently, we characterized the gene encoding a new member of this family, the 3'-nucleotidase/nuclease (Ld3'NT/NU) of the parasitic protozoan Leishmania donovani. The Ld3'NT/NU is unique as it is the only class I nuclease that is a cell surface membrane-anchored protein. Currently, we used a homologous episomal expression system to dissect the functional domains of the Ld3'NT/NU. Our results showed that its N-terminal signal peptide targeted this protein into the endoplasmic reticulum. Using Ld3'NT/NU-green fluorescent protein chimeras, we showed that the C-terminal domain of the Ld3'NT/NU functioned to anchor this protein into the parasite cell surface membrane. Further, removal of the Ld3'NT/NU C-terminal domain resulted in its release/secretion as a fully active enzyme. Moreover, deletion of its single N-linked glycosylation site showed that such glycosylation was not required for the enzymatic functions of the Ld3'NT/NU. Thus, using the fidelity of a homologous expression system, we have defined some of the functional domains of this unique member of the class I nuclease family.A2rel: a constitutively expressed Leishmania gene linked to an amastigote-stage-specific gene
AbstractGhedin, E., Charest, H., & Matlashewski, G. (n.d.).Publication year
1998Journal title
Molecular and Biochemical ParasitologyVolume
93Issue
1Page(s)
23-29AbstractThe A2-A2rel gene copies are arranged in tandem arrays on a 850 kb chromosome in Leishmania donovani. Contrary to A2 mRNA which displays amastigote-stage-specific expression, A2rel gene expression is constitutive throughout the L. donovani life cycle. The A2rel sequence was found to be conserved in all Leishmania species tested, while the A2 sequence is specific to L. donovani and L. mexicana.The A2rel full length cDNA is of 2.3 kb and it contains one open reading frame coding for a putative protein of 436 amino acids. Copyright (C) 1998 Elsevier Science B.V.Inducible expression of suicide genes in Leishmania donovani amastigotes
AbstractGhedin, E., Charest, H., Zhang, W. W., Debrabant, A., Dwyer, D., & Matlashewski, G. (n.d.).Publication year
1998Journal title
Journal of Biological ChemistryVolume
273Issue
36Page(s)
22997-23003AbstractThis study tests the feasibility of using the A2 gene regulatory system to create a Leishmania cell line in which attenuation is developmentally regulated when the parasite differentiates from promastigotes to amastigotes. The Leishmania donovani- inducible A2 gene regulatory system was used to differentially express in amastigotes two potential suicide genes: a truncated version of the L. donovani 3'-nucleotidase/nuclease expressed in the cytoplasm and the herpes simplex virus thymidine kinase gene. These genes were inserted between A2 noncoding regulatory sequences for up-regulation of expression in amastigotes. The accumulation of toxic products affected L. donovani cell replication and viability both in vitro and in vivo. The inducible expression of toxic gene products represents a valuable tool for the development of safe and effective vaccines.Antibody response against a Leishmania donovani amastigote-stage-specific protein in patients with visceral leishmaniasis
AbstractGhedin, E., Zhang, W. W., Charest, H., Sundar, S., Kenney, R. T., & Matlashewski, G. (n.d.).Publication year
1997Journal title
Clinical and Diagnostic Laboratory ImmunologyVolume
4Issue
5Page(s)
530-535AbstractThe antibody response against an amastigote-specific protein (A2) from Leishmania donovani was investigated. Sera from patients with trypanosomiasis and various forms of leishmaniasis were screened for anti-A2 antibodies. Sera from patients infected only with L. donovani or Leishmania mexicana specifically recognized the A2 recombinant protein. These results were consistent with karyotype analyses which revealed that the A2 gene is conserved in L. donovani and L. mexicana strains. The potential of this antigen in diagnosis was further explored by screening a series of sera obtained from patients in regions of the Sudan and India where L. donovani is endemic. The prevalence of anti-A2 antibodies was determined by Western blotting for all samples. Enzyme-linked immunosorbent assay (ELISA) and an immunoprecipitation assay were also performed on some of the samples. Anti-A2 antibodies were detected by ELISA in 82 and 60% of the samples from individuals with active visceral leishmaniasis (kala-azar) from the Sudan and India, respectively, while the immunoprecipitation assay detected the antibodies in 92% of the samples from India. These data suggest that the A2 protein may be a useful diagnostic antigen for visceral leishmaniasis.Identification and overexpression of the A2 amastigote-specific protein in Leishmania donovani
AbstractZhang, W. W., Charest, H., Ghedin, E., & Matlashewski, G. (n.d.).Publication year
1996Journal title
Molecular and Biochemical ParasitologyVolume
78Issue
1Page(s)
79-90AbstractLeishmania protozoa must adapt rapidly to widely different environments and thus exist as promastigotes in their sandfly host and as amastigotes in their mammalian host. Promastigote differentiation into amastigotes is accompanied by both morphological and biological changes. The molecular mechanisms regulating the differentiation and survival of the different life cycle stages are poorly understood. We have therefore undertaken to identify and characterized amastigote-specific genes and their corresponding products based on the rationale that such products may be involved in the survival in the mammalian host. Previously studies in our laboratory have revealed that the A2 gene family-derived transcripts are abundant in L. donovani amastigotes but are barely detectable in promastigotes. In the present study, we have raised polyclonal and monoclonal antibodies against a recombinant A2 protein synthesized in Escherichia coli. These antibodies have been used to identify a family of A2 proteins ranging from 45 kDa to about 100 kDa which are specifically detected in L. donovani cells when they are cultured in 37°C, and pH 4.5 (conditions which mimic the macrophage phagolysosome) but not in promastigotes cultured at 26°C and pH 7.4.A2 protein therefore represents a unique amastigote-specific protein marker for L. donovani. It is also demonstrated that it was possible to overexpress the A2 protein specifically in amastigote-like cells using a plasmid construct containing the A2 coding and non-coding sequences. These advances set the foundation for defining the biological function of the A2 protein and other genes when specifically expressed in amastigotes.Quality of drinking water sources in two sub-desert sahelian areas in north-western Senegal
AbstractGhedin, E., Robidoux, L., & Schmit, J. P. (n.d.).Publication year
1993Journal title
International Journal of Environmental StudiesVolume
44Issue
2Page(s)
113-130AbstractIn the course of the agricultural valorization of the Senegal River Valley, the improvement in clean water supply of villages comprised within agriculture zones came as a secondary goal. This study compares water quality between traditional wells and modern sources, such as boreholes and new dug wells, of two village zones located on the left bank of the river. Specific water sources were sampled at three periods of the year, and water quality was assessed. Since water is an important vector of numerous infectious diseases, emphasis was put on the quantitative evaluation of faecal organisms (faecal coliforms and streptococci), indicators of a human and animal contamination of the sources. Physico-chemical parameters and inorganic compounds complete the general evaluation. Results indicate that the analysed modem water sources are highly contaminated as compared to traditional sources. Modernization of water sources is not a sufficient measure for the improvement in clean water supplies. Users have a strong influence on the quality of their drinking water, rendering the education of dwellers, concerning management of their sources, an important consideration not to be overlooked in the process of improving the supply in clean water.