@article {49794,
	title = {Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during Intracellular Infection.},
	journal = {PLoS Pathog},
	volume = {12},
	year = {2016},
	month = {2016 Apr},
	pages = {e1005511},
	abstract = {<p>Intracellular colonization and persistent infection by the kinetoplastid protozoan parasite, Trypanosoma cruzi, underlie the pathogenesis of human Chagas disease. To obtain global insights into the T. cruzi infective process, transcriptome dynamics were simultaneously captured in the parasite and host cells in an infection time course of human fibroblasts. Extensive remodeling of the T. cruzi transcriptome was observed during the early establishment of intracellular infection, coincident with a major developmental transition in the parasite. Contrasting this early response, few additional changes in steady state mRNA levels were detected once mature T. cruzi amastigotes were formed. Our findings suggest that transcriptome remodeling is required to establish a modified template to guide developmental transitions in the parasite, whereas homeostatic functions are regulated independently of transcriptomic changes, similar to that reported in related trypanosomatids. Despite complex mechanisms for regulation of phenotypic expression in T. cruzi, transcriptomic signatures derived from distinct developmental stages mirror known or projected characteristics of T. cruzi biology. Focusing on energy metabolism, we were able to validate predictions forecast in the mRNA expression profiles. We demonstrate measurable differences in the bioenergetic properties of the different mammalian-infective stages of T. cruzi and present additional findings that underscore the importance of mitochondrial electron transport in T. cruzi amastigote growth and survival. Consequences of T. cruzi colonization for the host include dynamic expression of immune response genes and cell cycle regulators with upregulation of host cholesterol and lipid synthesis pathways, which may serve to fuel intracellular T. cruzi growth. Thus, in addition to the biological inferences gained from gene ontology and functional enrichment analysis of differentially expressed genes in parasite and host, our comprehensive, high resolution transcriptomic dataset provides a substantially more detailed interpretation of T. cruzi infection biology and offers a basis for future drug and vaccine discovery efforts.</p>},
	issn = {1553-7374},
	doi = {10.1371/journal.ppat.1005511},
	author = {Li, Yuan and Shah-Simpson, Sheena and Okrah, Kwame and Belew, A Trey and Choi, Jungmin and Caradonna, Kacey L and Padmanabhan, Prasad and Ndegwa, David M and Temanni, M Ramzi and Corrada Bravo, Hector and El-Sayed, Najib M and Burleigh, Barbara A}
}
@article {49539,
	title = {Transcriptomic profiling of gene expression and RNA processing during Leishmania major differentiation.},
	volume = {43},
	year = {2015},
	month = {2015 Aug 18},
	pages = {6799-813},
	abstract = {<p>Protozoan parasites of the genus Leishmania are the etiological agents of leishmaniasis, a group of diseases with a worldwide incidence of 0.9-1.6 million cases per year. We used RNA-seq to conduct a high-resolution transcriptomic analysis of the global changes in gene expression and RNA processing events that occur as L. major transforms from non-infective procyclic promastigotes to infective metacyclic promastigotes. Careful statistical analysis across multiple biological replicates and the removal of batch effects provided a high quality framework for comprehensively analyzing differential gene expression and transcriptome remodeling in this pathogen as it acquires its infectivity. We also identified precise 5{\textquoteright} and 3{\textquoteright} UTR boundaries for a majority of Leishmania genes and detected widespread alternative trans-splicing and polyadenylation. An investigation of possible correlations between stage-specific preferential trans-splicing or polyadenylation sites and differentially expressed genes revealed a lack of systematic association, establishing that differences in expression levels cannot be attributed to stage-regulated alternative RNA processing. Our findings build on and improve existing expression datasets and provide a substantially more detailed view of L. major biology that will inform the field and potentially provide a stronger basis for drug discovery and vaccine development efforts.</p>},
	issn = {1362-4962},
	doi = {10.1093/nar/gkv656},
	author = {Dillon, Laura A L and Okrah, Kwame and Hughitt, V Keith and Suresh, Rahul and Li, Yuan and Fernandes, Maria Cecilia and Belew, A Trey and Corrada Bravo, Hector and Mosser, David M and El-Sayed, Najib M}
}
