Areas of expertise
Infectious Diseases and RNA Biology , Functional genomics , Inflammation , Toxoplasmosis
Dr. Maritza Jaramillo received her undergraduate degree in Biology from Universidad Nacional de Colombia (Bogotá, Colombia). Subsequently, she completed her MSc and PhD in Microbiology and Immunology at Université Laval (Quebec, QC, Canada) under the supervision of Dr. Martin Olivier. During his graduate studies, Dr. Jaramillo worked on the transcriptional regulation of pro-inflammatory molecules induced during protozoan parasitic infections. Subsequently, she began her postdoctoral research in Dr. Nahum Sonenberg’s laboratory at McGill University (Montreal, QC, Canada), where she worked on translational control of infectious diseases. In May 2012 Dr. Jaramillo joined the Faculty of INRS – Centre Armand-Frappier Santé Biotechnologie (CAFSB) as an Assistant Professor to investigate the mechanisms and the functional consequences of dysregulated mRNA metabolism during toxoplasmosis. In May 2018 Dr. Jaramillo was granted tenure and was promoted to the rank of Associate Professor.
Role of dysregulated mRNA turnover and protein synthesis in the pathogenesis of congenital toxoplasmosis
Congenital toxoplasmosis is an infectious disease caused by Toxoplasma gondii (T. gondii), an obligate intracellular parasite commonly transmitted to humans by ingestion of contaminated raw meat, water, or soil. During pregnancy, T. gondii infection can lead to miscarriage, premature births, or serious birth defects (e.g. blindness, hydrocephalus, and mental retardation). It is estimated that ~30-40% of the world population is seropositive and that >90% of women in childbearing age are at risk of contractingthe parasite. Unfortunately, efficient and safe vaccines are lacking and available treatments often display teratogenic side effects. Hence, it has become critical to understand the molecular mechanisms underlying the interactions between T. gondii and the infected patient, particularly at the mother/fetus interface. In light of this problem, Dr. Jaramillo’s group investigates how dysregulation of host mRNA turnover and protein synthesis during T. gondii infection contributes to disrupt normal functions of placental cell populations including resident macrophages and trophoblasts, which are essential for embryo implantation and fetal development. Her studies also rely on the use of clinical samples from infected pregnant women and the ex vivo model of placental explants obtained from healthy donors. These valuable resources help validate data obtained in vitro and assess the implications of such findings in a clinical setting. Dr. Jaramillo’s long-term goal is to advance our understanding of the biological underpinnings implicated during congenital toxoplasmosis and to devise ways to thwart T. gondii transmission to promote healthy pregnancies.
Post-transcriptional regulation of host gene expression during Leishmania infection
Protozoan parasites of the genus Leishmania are the causative agents of leishmaniasis, a group of diseases with clinical symptoms ranging from skin lesions to visceral pathologies that can lead to death if left untreated. Unfortunately no effective vaccine has been developed yet and drug resistance is rapidly increasing. Therefore, the current situation reflects an urgent need to better understand the molecular basis of interactions between Leishmania and its host cell. In infectious diseases, the regulation of mRNA translation allows cells to quickly adjust their proteomes but can also be exploited by the invading pathogen. Leishmania lives inside immune cells called macrophages, one of the most powerful lines of defense against microbial invasion. To survive in this environment, the parasite modulates numerous intracellular signals necessary for the activation of the transcription of genes linked to the immune response. As a result, many functions of the macrophage are affected. Using a genome-wide approach (polysome profiling coupled to RNA-seq), Dr. Jaramillo’s team recently demonstrated that in addition to modifying transcription, Leishmania selectively deregulates mRNA translation in macrophages (Chaparro, Leroux et al. 2020 PLoS Pathogens https://doi.org/10.1371/journal.ppat.1008291). Bioinformatics analyses of identified transcripts suggest that key metabolic, immune and microbicidal functions are hijacked by Leishmania via the modulation of host mRNA translation. Based on these results current projects in Dr. Jaramillo’s laboratory aim to further investigate the mechanisms and functional consequences of the alteration of host mRNA translation in the progression of the disease. To this end, her team utilizes in vitro and in vivo infection models, clinical Leishmania isolates, patient samples from endemic regions, mutant cell lines and transgenic mice in combination with Omics approaches (RNA -seq, CLIP-seq, BRIC-seq, proteomics). These studies will help identify new regulatory nodes of gene expression in macrophages that might contribute to design effective and safe treatments to reduce morbidity and mortality associated with leishmaniasis.
Currently, Dr. Jaramillo’s research program is funded by a CIHR Project Grant (OCT/2019 – SEP/2025) and an NSERC Discovery Grant (APR/2019 – MAR/2025).
Leroux LP1, Chaparro V, Jaramillo M1. 2020. Infection by the protozoan parasite Toxoplasma gondii inhibits host MNK1/2-eIF4E axis to promote its survival. Front Cell Infect Microbiol 10:488. 1Corresponding author. https://doi.org/10.3389/fcimb.2020.00488
Chaparro V1, Leroux LP1, Masvidal L, Lorent J, Graber TE, Zimmermann A, Arango Duque G, Descoteaux A, Alain T, Larsson O, Jaramillo M2. 2020. Translational profiling of macrophages infected with Leishmania donovani identifies mTOR- and eIF4A-sensitive immune-related transcripts. PLoS Pathogens 16: e1008291. 1Equal contribution, 2Corresponding author. https://doi.org/10.1371/journal.ppat.1008291
Pearl D, Katsumura S, Amiri M, Zhang X, Vinette V, Pang X, Beug S, Kim SH, Jones L, Robichaud N, Ong SG, Jia JJ, Ali H, Tremblay MJ, Jaramillo M, Alain T, Morita M, Tahmasebi S, Sonenberg, N. 2020. 4E-BP-dependent translational control of Irf8 mediates adipose tissue macrophage inflammatory response. J Immunol 204:2392-2400 https://doi.org/10.4049/jimmunol.1900538
Hoang HD1, Graber TE1, Jia JJ, Vaidya N, Gilchrist V, Li W, Gkogkas CG, Jaramillo M, Jafarnejad SM, Alain, T. 2019. Induction of an alternative 5’ leader enhances translation of Inpp5e and resistance to oncolytic virus infection. Cell Rep 29:4010-4023.e5. 1Equal contribution. https://doi.org/10.1016/j.celrep.2019.11.072
William M1, Leroux LP1,2, Chaparro V, Graber TE, Alain T, Jaramillo M2. 2019. Translational repression of Ccl5 and Cxcl10 by 4E-BP1 and 4E-BP2 restrains the ability of mouse macrophages to induce migration of activated T cells. Eur J Immunol 49: 1200-1212. 1Equal contribution, 2Corresponding author. https://doi.org/10.1002/eji.201847857
Chaparro V, Leroux LP, Zimmermann A, Jardim A, Johnston B, Descoteaux A, Jaramillo M1. 2019. Leishmania donovani lipophosphoglycan increases macrophage-dependent chemotaxis of CXCR6-expressing cells via CXCL16 induction. Infect Immun 87: e00064-19. 1Corresponding author. https://dx.doi.org/10.1128%2FIAI.00064-19
Atayde V, da Silva Lira Filho A, Chaparro V, Zimmermann A, Jaramillo M, Olivier M. 2019. Exploitation of the Leishmania exosomal pathway by Leishmania RNA virus 1. Nat Microbiol. 4: 714-723 https://doi.org/10.1038/s41564-018-0352-y
Leroux LP, Nasr M, Valanparambil R, Tam M, Rosa BA, Siciliani D, Hill DE, Zarlenga DS, Jaramillo M, Weinstock JV, Geary TG, Stevenson MM, Urban JF, Makedonka M, Jardim A. 2018. Analysis of the Trichuris suis excretory/secretory proteins as a function of life cycle stage and their immunomodulatory properties. Sci Rep 8:15921 https://doi.org/10.1038/s41598-018-34174-4
Zakaria C, Sean P, Hoang HD, Leroux LP, Watson M, Workenhe ST, Hearnden J, Pearl D, Truong TV, Robichaud N, Yanagiya A, Tahmasebi S, Jafarnejad SM, Jia JJ, Graber TE, Fonseca BD, Pelin A, Diallo JS, Le Boeuf F, Bell JC, Mossman K, Jaramillo M, Sonenberg N, Alain T. 2018. Active-Site mTOR inhibitors augment HSV1 infection of cancer cells with elevated eIF4E activity. PLoS Pathog 14: e1007264 https://doi.org/10.1371/journal.ppat.1007264
Leroux LP, Lorent J, Graber TE, Chaparro V, Masvidal L, Aguirre M, Fonseca BD, van Kempen LC, Alain T, Larsson O, Jaramillo M1. 2018. The protozoan parasite Toxoplasma gondii selectively reprograms the host translatome. Infect Immun 86: e00244-18. 1Corresponding author. https://doi.org/10.1128/iai.00244-18
William M, Leroux LP, Lorent J, Chaparro V, Graber TE, M’Boutchou MN, Charpentier T, Fabié A, Dozois CM, Stäger S, van Kempen LC, Alain T, Larsson O, Jaramillo M1. 2018. eIF4E-binding proteins 1 and 2 limit macrophage anti-inflammatory responses through translational repression of Interleukin-10 and Cyclooxygenase-2. J Immunol 200: 4102-4116. 1Corresponding author. https://doi.org/10.4049/jimmunol.1701670
Bhat M, Yanagiya A, Graber TE, Razumilava N, Bronk S, Zammit D, Zhao Y, Zakaria C, Metrakos P, Pollak M, Sonenberg N, Gores G, Jaramillo M, Morita M, Alain T. 2016. Metformin requires 4E-BPs to induce apoptosis and repress translation of Mcl-1 in hepatocellular carcinoma cells. Oncotarget 8: 50542-56 https://doi.org/10.18632/oncotarget.10671
Liberman N, Gandin V, Svitkin YV, David M,Virgili G, Jaramillo M, Holcik M, Nagar B, Kimchi A, Sonenberg N. 2015. DAP5 associates with eIF2β and eIF4AI to promote Internal Ribosome Entry Site driven translation. Nucl Acids Res 43: 3764-75 https://doi.org/10.1093/nar/gkv205
Nehdi A, Sean P, Linares I, Colina R, Jaramillo M, Alain T. 2014. Deficiency in either 4E-BP1 or 4E-BP2 augments innate antiviral immune responses. PLoS ONE 9 e114854 https://doi.org/10.1371/journal.pone.0114854
Herdy B1, Jaramillo M1, Svitkin YV, Rosenfeld A, Kobayashi M, Walsh D, Alain T, Robichaud N, Topisirovic I, Furic L, Dowling RJO, Sylvestre A, Rong L, Colina R, Costa-Mattioli M, Fritz JH, Olivier M, Brown E, Mohr I, Sonenberg N. 2012. Translational control of the activation of transcription factor NF-kappaB and production of type I interferon by phosphorylation of the translation factor eIF4E. Nat Immunol 13: 543-50. 1Equal contribution. https://doi.org/10.1038/ni.2291
Jaramillo M, Gomez MA, Larsson O, Shio MT, Topisirovic I, Contreras I, Luxenburg R, Rosenfeld A, Colina R, McMaster R, Olivier M, Costa-Mattioli M, Sonenberg N. 2011. Leishmania repression of host translation through mTOR cleavage is required for parasite survival and infection. Cell Host Microbe 9: 331-41 https://doi.org/10.1016/j.chom.2011.03.008
Chartrand P, Jaramillo M, Gamberi C. 2020. Editorial: RNA Regulation in Development and Disease. Frontiers in Genetics https://doi.org/10.3389/fgene.2020.00430