Professor of Epidemiology
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.
BS, Biology, McGill University, Montreal, CanadaMS, Environmental Sciences, University of Quebec, Montreal, CanadaPhD, Molecular Parasitology, McGill University, Montreal, Canada
American Academy of Microbiology Fellow (2017)Kavli Frontiers of Science Fellow (2012)MacArthur Fellow (2011)Chancellor’s Distinguished Research Award (2010)
BiologyGenomicsInfectious DiseasesViral Infections
Reply to ‘Reconciling disparate estimates of viral genetic diversity during human influenza infections’Poon, L. L., Song, T., Wentworth, D. E., Holmes, E. C., Greenbaum, B. D., Peiris, J. S., Cowling, B. J., & Ghedin, E. [Personal communication]. In , & , Nature Genetics.
Getting the flu: 5 key facts about influenza virus evolutionJohnson, K. E., Song, T., Greenbaum, B., & Ghedin, E.
Journal titlePLoS Pathogens
The lung mycobiome in the next-generation sequencing eraTipton, L., Ghedin, E., & Morris, A.
Page(s)334-341The fungi that reside in the human lungs represent an understudied, but medically relevant comm-unity. From the few studies published on the lung mycobiome, we find that there are fungi in both the healthy and diseased respiratory tract, that these fungi vary widely between individuals, and that there is a trend toward lower fungal diversity among individuals with disease. This review discusses the few studies of the lung mycobiome and details the challenges that accompany lung mycobiome studies. These challenges include sample collection and processing, sequence amplification and processing, and a history of multiple names for species. Some challenges may never be solved, but others can be solved with more data and additional studies of the lung mycobiome.
The role of 'omics' in the quest to eliminate human filariasisLustigman, S., Grote, A., & Ghedin, E.
Journal titlePLoS neglected tropical diseases
Network inference from multimodal data: A review of approaches from infectious disease transmissionRay, B., Ghedin, E., & Chunara, R.
Journal titleJournal of Biomedical Informatics
Page(s)44-54Networks inference problems are commonly found in multiple biomedical subfields such as genomics, metagenomics, neuroscience, and epidemiology. Networks are useful for representing a wide range of complex interactions ranging from those between molecular biomarkers, neurons, and microbial communities, to those found in human or animal populations. Recent technological advances have resulted in an increasing amount of healthcare data in multiple modalities, increasing the preponderance of network inference problems. Multi-domain data can now be used to improve the robustness and reliability of recovered networks from unimodal data. For infectious diseases in particular, there is a body of knowledge that has been focused on combining multiple pieces of linked information. Combining or analyzing disparate modalities in concert has demonstrated greater insight into disease transmission than could be obtained from any single modality in isolation. This has been particularly helpful in understanding incidence and transmission at early stages of infections that have pandemic potential. Novel pieces of linked information in the form of spatial, temporal, and other covariates including high-throughput sequence data, clinical visits, social network information, pharmaceutical prescriptions, and clinical symptoms (reported as free-text data) also encourage further investigation of these methods. The purpose of this review is to provide an in-depth analysis of multimodal infectious disease transmission network inference methods with a specific focus on Bayesian inference. We focus on analytical Bayesian inference-based methods as this enables recovering multiple parameters simultaneously, for example, not just the disease transmission network, but also parameters of epidemic dynamics. Our review studies their assumptions, key inference parameters and limitations, and ultimately provides insights about improving future network inference methods in multiple applications.
Myxoma virus and the leporipoxviruses: An evolutionary paradigmKerr, P. J., Liu, J., Cattadori, I., Ghedin, E., Read, A. F., & Holmes, E. C.
Page(s)1020-1061Myxoma virus (MYXV) is the type species of the Leporipoxviruses, a genus of Chordopoxvirinae, double stranded DNA viruses, whose members infect leporids and squirrels, inducing cutaneous fibromas from which virus is mechanically transmitted by biting arthropods. However, in the European rabbit (Oryctolagus cuniculus), MYXV causes the lethal disease myxomatosis. The release of MYXV as a biological control for the wild European rabbit population in Australia, initiated one of the great experiments in evolution. The subsequent coevolution of MYXV and rabbits is a classic example of natural selection acting on virulence as a pathogen adapts to a novel host species. Slightly attenuated mutants of the progenitor virus were more readily transmitted by the mosquito vector because the infected rabbit survived longer, while highly attenuated viruses could be controlled by the rabbit immune response. As a consequence, moderately attenuated viruses came to dominate. This evolution of the virus was accompanied by selection for genetic resistance in the wild rabbit population, which may have created an ongoing co-evolutionary dynamic between resistance and virulence for efficient transmission. This natural experiment was repeated on a continental scale with the release of a separate strain of MYXV in France and its subsequent spread throughout Europe. The selection of attenuated strains of virus and resistant rabbits mirrored the experience in Australia in a very different environment, albeit with somewhat different rates. Genome sequencing of the progenitor virus and the early radiation, as well as those from the 1990s in Australia and Europe, has shown that although MYXV evolved at high rates there was no conserved route to attenuation or back to virulence. In contrast, it seems that these relatively large viral genomes have the flexibility for multiple pathways that converge on a similar phenotype.
Viral evolution: Beyond drift and shiftGreenbaum, B. D., & Ghedin, E.
Journal titleCurrent Opinion in Microbiology
Page(s)109-115Technological advances have allowed aspects of viral evolution to be explored at unprecedented scales. As a consequence, new quantitative approaches are needed to investigate features of viral evolution that fall outside traditional areas of study, such as antigenic evolution. We examine three areas of viral evolution where tools from disciplines such as statistical physics, topology, and information theory have been used recently as quantitative frameworks for large-scale studies and, in some cases, suggest a novel theoretical approach to a problem. Ongoing interaction among these disciplines with biology is necessary so that experimental researchers can determine which quantitative tools are right for them and quantitative researchers can learn which aspects of viral evolution can be understood and advanced with their approaches.
Panning for molecular gold in whipworm genomesGhedin, E.
Journal titleNature Genetics
Page(s)661-663Two new studies report genomic data on three species of whipworm, soil-transmitted parasitic worms responsible for trichuriasis. These genomes provide insights into host-pathogen interactions and potential for new drug targets for helminth therapy.
The microbiome and the lungCui, L., Morris, A., Huang, L., Beck, J. M., Twigg, H. L., Von Mutius, E., & Ghedin, E.
Journal titleAnnals of the American Thoracic Society
Page(s)S227-S232Investigation of the human microbiome has become an important field of research facilitated by advances in sequencing technologies. The lung, which is one of the latest body sites being explored for the characterization of human-associated microbial communities, has a microbiome that is suspected to play a substantial role in health and disease. In this review, we provide an overview of the basics of microbiome studies. Challenges in the study of the lung microbiome are highlighted, and further attention is called to the optimization and standardization of methodologies to explore the role of the lung microbiome in health and disease. We also provide examples of lung microbial communities associated with disease or infection status and discuss the role of fungal species in the lung. Finally, we review studies demonstrating that the environmental microbiome can in fluence lung health and disease, such as the finding that the diversity of microbial exposure correlates inversely with the development of childhood asthma.
The human mycobiome in health and diseaseCui, L., Morris, A., & Ghedin, E.
Journal titleGenome Medicine
Issue7The mycobiome, referring primarily to the fungal biota in an environment, is an important component of the human microbiome. Despite its importance, it has remained understudied. New culture-independent approaches to determine microbial diversity, such as next-generation sequencing methods, are greatly broadening our view of fungal importance. An integrative analysis of current studies shows that different body sites harbor specific fungal populations, and that diverse mycobiome patterns are associated with various diseases. By interfacing with other biomes, as well as with the host, the mycobiome probably contributes to the progression of fungus-associated diseases and plays an important role in health and disease.
Use of bronchoalveolar lavage to assess the respiratory microbiome: Signal in the noiseTwigg, H. L., Morris, A., Ghedin, E., Curtis, J. L., Huffnagle, G. B., Crothers, K., Campbell, T. B., Flores, S. C., Fontenot, A. P., Beck, J. M., Huang, L., Lynch, S., Knox, K. S., & Weinstock, G. [Personal communication]. In , & , The Lancet Respiratory Medicine.
Filarial and Wolbachia genomicsScott, A. L., Ghedin, E., Nutman, T. B., McReynolds, L. A., Poole, C. B., Slatko, B. E., & Foster, J. M.
Journal titleParasite Immunology
Page(s)121-129Filarial nematode parasites, the causative agents for a spectrum of acute and chronic diseases including lymphatic filariasis and river blindness, threaten the well-being and livelihood of hundreds of millions of people in the developing regions of the world. The 2007 publication on a draft assembly of the 95-Mb genome of the human filarial parasite Brugia malayi- representing the first helminth parasite genome to be sequenced - has been followed in rapid succession by projects that have resulted in the genome sequencing of six additional filarial species, seven nonfilarial nematode parasites of animals and nearly 30 plant parasitic and free-living species. Parallel to the genomic sequencing, transcriptomic and proteomic projects have facilitated genome annotation, expanded our understanding of stage-associated gene expression and provided a first look at the role of epigenetic regulation of filarial genomes through microRNAs. The expansion in filarial genomics will also provide a significant enrichment in our knowledge of the diversity and variability in the genomes of the endosymbiotic bacterium Wolbachia leading to a better understanding of the genetic principles that govern filarial-Wolbachia mutualism. The goal here is to provide an overview of the trends and advances in filarial and Wolbachia genomics.
Large-scale sequencing and the natural history of model human RNA virusesDugan, V. G., Saira, K., & Ghedin, E.
Journal titleFuture Virology
Page(s)563-573RNA virus exploration within the field of medical virology has greatly benefited from technological developments in genomics, deepening our understanding of viral dynamics and emergence. Large-scale first-generation technology sequencing projects have expedited molecular epidemiology studies at an unprecedented scale for two pathogenic RNA viruses chosen as models: influenza A virus and dengue. Next-generation sequencing approaches are now leading to a more in-depth analysis of virus genetic diversity, which is greater for RNA than DNA viruses because of high replication rates and the absence of proofreading activity of the RNA-dependent RNA polymerase. In the field of virus discovery, technological advancements and metagenomic approaches are expanding the catalogs of novel viruses by facilitating our probing into the RNA virus world.
It's a small world after all - Viral genomics and the global dominance of virusesGhedin, E., & Upton, C.
Journal titleCurrent Opinion in Virology
Helminth genomics: The implications for human healthBrindley, P. J., Mitreva, M., Ghedin, E., & Lustigman, S.
Journal titlePLoS neglected tropical diseases
Issue10More than two billion people (one-third of humanity) are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings.
The genome of Brugia malayi - All worms are not created equalScott, A. L., & Ghedin, E.
Journal titleParasitology International
Page(s)6-11Filarial nematode parasites, the causative agents of elephantiasis and river blindness, undermine the livelihoods of over one hundred million people in the developing world. Recently, the Filarial Genome Project reported the draft sequence of the ~ 95 Mb genome of the human filarial parasite Brugia malayi - the first parasitic nematode genome to be sequenced. Comparative genome analysis with the prevailing model nematode Caenorhabditis elegans revealed similarities and differences in genome structure and organization that will prove useful as additional nematode genomes are completed. The Brugia genome provides the first opportunity to comprehensively compare the full gene repertoire of a free-living nematode species and one that has evolved as a human pathogen. The Brugia genome also provides an opportunity to gain insight into genetic basis for mutualism, as Brugia, like a majority of filarial species, harbors an endosybiotic bacterium (Wolbachia). The goal of this review is to provide an overview of the results of genomic analysis and how these observations provide new insights into the biology of filarial species.
The symbiotic relationship between filarial parasitic nematodes and their Wolbachia endosymbionts - A resource for a new generation of control measuresGhedin, E., Daehnel, K., Foster, J., Slatko, B., & Lustigman, S.
Page(s)77-85Filarial parasites are responsible for millions of human infections each year, mostly in developing parts of the world. International programs supported largely by the World Health Organization have worked to control the impact of onchocerciasis and lymphatic filariasis using mass administration of single or combination drugs for long periods of time in eligible populations. The success of these programs is now being hampered by the probability of programmatic failure in the event of emerging drug resistance. Additional research is critically needed to develop a new generation of tools for the control and treatment of these infections. These would include drugs that target adult worms and vaccines, with the goal to overcome potential resistance to the currently available drugs and complement present control measures. The majority of human filarial parasites carry intracellular symbiotic bacteria, Wolbachia, that appear to be essential for development and reproduction of the parasite. The recent availability of genomic data for both filaria and Wolbachia provides insight into essential aspects of the symbiotic relationship between the endosymbiont and its nematode host. We present an overview of how this knowledge opens up avenues in the identification of new targets for the control of these parasitic infections.
Shared data are key to beating threat from flu Salzberg, S., Ghedin, E., & Spiro, D. [Personal communication]. In , & , Nature.
Genomic and proteomic approaches for Chagas' disease: Critical analysis of diagnostic methodsHuete-Pérez, J. A., Flores-Obando, R. E., Ghedin, E., & Caffrey, C. R.
Journal titleExpert Review of Molecular Diagnostics
Page(s)521-530Trypanosoma cruzi is the etiologic agent of Chagas' disease, a chronic inflammatory condition that results in heart and digestive complications. The first draft of the parasite genome is now complete and it is expected that, along with the published genomic and proteomic analyses discussed herein, it will lead to the identification of crucial genes and proteins directly associated with disease. This article reviews the current research trends addressing host-parasite interaction, parasite genetic variability and diagnosis. These advances will certainly bring about major developments not only in our understanding of Trypanosoma cruzi biology, but also in the application of new technologies to disease prevention and control.
Mechanisms of HTLV-1 transformation.Kehn, K., Berro, R., De La Fuente, C., Strouss, K., Ghedin, E., Dadgar, S., Bottazzi, M. E., Pumfery, A., & Kashanchi, F.
Journal titleFrontiers in bioscience : a journal and virtual library
Page(s)2347-2372HTLV-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.Seelamgari, A., Maddukuri, A., Berro, R., De La Fuente, C., Kehn, K., Deng, L., Dadgar, S., Bottazzi, M. E., Ghedin, E., Pumfery, A., & Kashanchi, F.
Journal titleFrontiers in bioscience : a journal and virtual library
Page(s)2388-2413Human 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.