Alejandro Escobar

University of Chile

NAME: Alejandro Escobar CITIZENSHIP: Chilean E-MAIL: a.escobar@odontologia.uchile.cl PHONE: +56988285501 POSITION TITLE: Associate professor. Institute for Research in Dental Sciences. Faculty of Dentistry. Universidad de Chile. EDUCATION/TRAINING: Universidad de Chile D.V.M. 01/2000 Veterinary Medicine Universidad de Chile M.Sc. 08/2004 Immunology Universidad de Chile Ph.D. 03/2010 Biomedical Sciences A. Personal Statement My current research aims at studying the host-pathogen interaction in the context of the evasion of immune response used by the pathogen Neisseria gonorrhoeae on antigen-presenting cells, particularly macrophages. These concepts may apply to inflammatory diseases caused by infections and may offer new approaches to treating human conditions. Also, I am very interested in research related to oral immunology, which has led to collaboration in immunity studies about periodontal disease and caries. I'm also working on the usefulness of alpha-2 macroglobulin (inflammation biomarker) and its diagnostic capacity in inflammatory conditions such as T2DM and IBD. B. Positions and Honors Positions and employment 2000-2001 Research Assistant, Immunology program. Biomedical Sciences Institute, Universidad de Chile. 2002-2004 Research Technician, Immunology program Biomedical Sciences Institute, Universidad de Chile. 2010 Veterinary Medical Advisor on laboratory animal welfare. Universidad de Santiago de Chile. 2011-2019 Assistant Professor. Institute for Research in Dental Sciences. Faculty of Dentistry. Universidad de Chile. 2020-Present Associate Professor. Institute for Research in Dental Sciences. Faculty of Dentistry. Universidad de Chile. Honors 2011 Young Talents Award for Veterinary Medical Researchers VET2011 Chile. 2007 Short stay abroad scholarship. Project MESESUP UCH #0306. 2007 Young Scientist Travel Grant for the 13th international Congress of Immunology. 2006 Council of Science and Technology (CONICYT) Grant #101287 Financing Postgraduate Studies C. Contributions to Science My contribution to the discipline of immunology has covered various aspects of the immune response against cancer, immunomodulation of the immune response in allergy, and antimicrobial immune response. I have addressed each of these areas at different stages of my training. The following publications reflect the achievements in this context. 1. Carolina Ortiz, Claudia Lefimil, Paula I Rodas, Rolando Vernal, Mercedes Lopez, Claudio Acuña-Castillo, Monica Imarai, Alejandro Escobar. Neisseria gonorrhoeae modulates immunity by polarizing human macrophages to a M2 profile. Plos one 2015; 10 (6): e0130713. doi: 10.1371 / journal.pone.0130713. This study was conducted entirely under my design and coordination, and it was with my first extramural funding. This work demonstrates that the bacterium Neisseria gonorrhoeae can induce an M2 phenotype in human monocyte-derived macrophages. Until this study, there were no reports of the effects of gonococcus on macrophage polarization. This study has important implications for understanding the mechanisms of the long-term persistence of N. gonorroheae infection and could apply to the development of new therapeutic strategies. 2. Alejandro Escobar, Enzo Candia, Sebastian Reyes-Cerpa, Belgium Villegas-Valdes, Tanya Neira, Mercedes Lopez, Kevin Maisey, Fabián Tempio, Miguel Ríos, Claudio Acuña-Castillo, Mónica Imarai. Neisseria gonorrhoeae induces a tolerogenic phenotype in macrophages to modulate host immunity. Mediators of inflammation 2013; 2013: 127017. This study was carried out in conjunction with Dra. Mónica Imarai. It is the first work that I coordinated. This work demonstrates in murine cell lines that the bacterium Neisseria gonorrhoeae interacts with macrophages by regulating their inflammatory activity and establishes the immune evasion mechanisms' bases in this cell type. 3. Alejandro Escobar, Paula I. Rodas, Claudio Acuña-Castillo. Macrophage–Neisseria gonorrhoeae Interactions: a better understanding of pathogen mechanisms of immunomodulation. Frontiers in Immunology 2018 21;9:3044. doi: 10.3389/fimmu.2018.03044. 4. Gatica J, Rodas PI, Escobar A. Use of Human Monocyte-Derived Macrophages to Study Neisseria gonorrhoeae Infection. Methods Mol Biol. 2019; 1997:301-318. doi: 10.1007/978-1-4939-9496-0_18. The peers have recognized the importance of this finding through an invitation to contribute to Research Topic from Frontiers in immunology and Methods in Molecular Biology book series. 5. Alejandro Escobar, María Antonieta Guzmán, Adam Aguirre, Rodrigo González, Diego Catalán, Claudio Acuña-Castillo, Jennifer M Rolland, Robyn O`Hehir, Juan Carlos Aguillón. Tolerogenic dendritic cells derived from donors with natural rubber latex allergy modulate allergen-specific T-cell responses and IgE production. PLoS One. 2014 Jan 22; 9 (1): e85930. My Ph.D. thesis explores the use of dendritic cells treated with dexamethasone in modulating the immune response in latex allergy. This work allowed me to establish international collaboration with Dr. Robyn O'Hehir, Director of the Immunology Department at Monash University, Australia. 6. Escobar A., López M., Aguirre A., Serrano A., González R., Larrondo M., Fodor M., Ferrada C., Salazar-Onfray F. (2005) Dendritic cells immunizations combined with low doses interleukin -2 induces immune responses in melanoma patients. Clinical and Experimental Immunology 142: 555-68. During the development of my Magister, I worked on the immune response against cancer. The results of my thesis allowed the development of a line of research in cellular immunotherapy against melanoma. This research concluded in the publication of the first clinical trial that established the effectiveness of immunotherapy in cancer in Chile.   D. Additional Information: Research Support 2007-2009 Principal investigator. Young Researchers Grant 238/07 Hospital Clínico Universidad de Chile, Immunology and Allergology Section. Regulatory dendritic cells in the modulation of the immune response in latex allergy. 2011-2014 Principal investigator. Grant #11110304 National Council of Science and Technology (CONICYT).Immune evasion by Neisseria gonorrhoeae: Implications of Th17 / Tregs balance and its modulation. 2012-2014. Principal Investigator. Fund for Research in Dentistry (FIOUCh). Faculty of Dentistry, Universidad de Chile. Validation of the alpha-2-macroglobulin biomarker in human saliva as a complementary tool for the metabolic control of patients with type 2 diabetes. 2016-2018 Principal investigator. Fund for Research in Dentistry (FIOUCh). Faculty of Dentistry, Universidad de Chile. Effect of topical use and ingestion of the probiotic Lactobacillus Rhamnosus SP1 on the oral immune response in saliva in a caries in situ models. 2018-2020 Principal Investigator Grant #1180666 National Council of Science and Technology (CONICYT) Exploring the role of programmed Cell Death-ligand (PD-L1) in Neisseria gonorrhoeae-infected macrophages and the use of anti-PD-L1 therapy as a novel approach to the treatment of gonorrhea in the era of antibiotic-resistant bacteria. Publications (last 5 years) Francisca Sandoval, Simone Faleiros, Rodrigo Cabello, Mario Díaz-Dosque, Gonzalo Rodríguez, Alejandro Escobar. The consumption of milk supplemented with probiotics decreases the occurrence of caries and the salivary concentration of hβD-3 in children. Clinical Oral Investigation 2021 DOI: 10.1007/s00784-020-03712-8. Claudia Robles-Planells, Carlos Barrera-Avalos, Leonel Rojo, Eugenio Spencer, Marcelo Cortez-San Cortez-San Martin, Silvia Beatriz Matiacevich, Jorge Pavez, Luis Milla, Franco D Navarro, Brandon A Martinez, Francisco J Bravo, Andrea Mella, Juan Pablo G. Huidobro-Toro, Ricardo Fernandez, Alejandro Escobar, Claudio Acuña-Castillo, and Eugenio Spencer. Chitosan-based delivery of Avian Reovirus fusogenic protein p-10 Gene: in vitro and in vivo studies towards a new vaccine against melanoma. BioMed Research International Volume 2020 Article ID 4045760. https://doi.org/10.1155/2020/4045760 Pablo Veloso, Alejandra Fernández, Claudia Terraza-Aguirre, Carla Álvarez, Rolando Vernal, Alejandro Escobar, Marcela Hernández. Macrophages skew towards M1 profile through reduced CD163 expression in symptomatic apical periodontitis. Clinical Oral Investigation 2020. https://doi.org/10.1007/s00784-020-03324-2 Claudia Robles-Planells, Giselle Sánchez, Carlos Barrera-Avalos, Silvia Beatriz Matiacevich, Leonel Rojo, Jorge Pavez, Edison Salas-Huenuleo, M. Kogan, Alejandro Escobar, Luis Milla, Ricardo Fernandez, Monica Imarai, Eugenio Spencer, Juan Pablo G. Huidobro-Toro, and Claudio Acuña-Castillo. Chitosan-based nanoparticles for intracellular delivery of ISAV fusion protein cDNA into melanoma cells: A path to develop oncolytic anticancer therapies. Mediators of inflammation. Volume 2020. Article ID 8680692. https://doi.org/10.1155/2020/8680692 Claudia Robles-Planells, Sofía A. Michelson, Javier Mena, Daniela Escrig, Juan L. Rojas, Giselle E. Sánchez Guerrero, Ronny Hernandez, Carlos E. Barrera, Leonel E. Rojo, Daniela Sauma, Alexis M. Kalergis, Monica Imarai, Ricardo Fernandez, Carolina A. Robles, Elias Leiva-Salcedo, Alejandro Escobar and Claudio Acuña-Castillo. 2019. Lithraea caustic (Litre) extract promotes an antitumor response against B16 melanoma. Front. Pharmacol 2019. doi: 10.3389/fphar.2019.01201. ISSN. 1663-9812 Berly Cahuascanco, Javiera Bahamonde, Olger Huaman, Miguel Jervis, Jahaira Cortez, Jaime Palomino, Alejandro Escobar, Patricio Retamal, Cristian G. Torres, Oscar Alejandro Peralta. Bovine fetal mesenchymal stem cells exert antiproliferative efect against mastitis causing pathogen Staphylococcus aureus. Veterinary Research 2019 50:25 https://doi.org/10.1186/s13567-019-0643-1 Alejandro Escobar, Paula I. Rodas, Claudio Acuña-Castillo. Macrophage–Neisseria gonorrhoeae Interactions: a better understanding of pathogen mechanisms of immunomodulation. Frontiers in Immunology 2018 21;9:3044. doi: 10.3389/fimmu.2018.03044. Escobar, G. Escobar, A. Ascui, G. Tempio, F. Ortiz, C. Perez, C. Lopez, M. Pure Platelet-rich Plasma and supernatant of calcium-activated P-PRP induce different phenotypes of human macrophages. Regen Med. 2018 13(4):427-441. doi: 10.2217/rme-2017-0122. Jonathan Morales, Carlos Barrera-Avalos, Carlos Castro, Stephanie Castillo, Claudio Barrientos, Claudia Robles-Planells, Ximena Lopez, Ernesto Torres, Margarita Montoya, Marcelo Cortez-San Martín, Denise Riquelme, Alejandro Escobar, Ricardo Fernandez, Monica Imarai, Daniela Sauma, Leonel E Rojo, Elias Leiva-Salcedo, Claudio Acuña-Castillo. Dead Tumor Cells expressing ISAV fusogenic protein favor antigen cross-priming in vitro. Frontiers in Immunology 2017 vol 8 article 1170. doi: 10.3389/fimmu.2017.01170. Killen García, Gisselle Escobar, Pablo Mendoza, Caroll Beltran, Claudio Perez, Sergio Arancibia, Rolando Vernal, Paula I Rodas, Claudio Acuña-Castillo, Alejandro Escobar. ATP induces IL-1ß secretion in Neisseria gonorrhoeae-infected human macrophages by a mechanism not related with the NLRP3/ASC/caspase-1 axis. Mediators of inflammation 2016; 2016 1258504 http://dx.doi.org/10.1155/2016/1258504. Rodas PI, Alamos-Musre AS, Álvarez FP, Escobar A, Tapia CV, Osorio E, Otero C, Calderón IL, Fuentes JA, Gil F, Paredes-Sabja D, Christodoulides M. The NarE protein of Neisseria gonorrhoeae catalyzes ADP-ribosylation of several ADP-ribose acceptors despite an N-terminus deletion. FEMS Microbiol Lett. 2016 Jul 26. pii: fnw181. Arancibia S, Barrientos A, Torrejón J, Escobar A, Beltrán CJ. Copper oxide nanoparticles recruit macrophages and modulate nitric oxide, proinflammatory cytokines and PGE2 production through arginase activation. Nanomedicine-UK (Lond). 2016 11(10):1237-51. Samanta Melgar-Rodríguez, Jaime Díaz-Zúñiga, Carla Alvarez, Leticia Rojas, Gustavo Monasterio, Paola Carvajal, Alejandro Escobar, Mariano Sanz and Rolando Vernal. Serotype b of Aggregatibacter actinomycetemcomitans increases osteoclast and memory T-lymphocyte activation. Mol Oral Microbiol. 2016 Apr;31(2):162-74. doi: 10.1111/omi.12112. Claudio A. Perez , Ramon Rabanales , Gonzalo Rojas-Alcayaga , Milton Larrondo , Alejandro F. Escobar, Mercedes N. Lopez, Flavio Salazar-Onfray, Jorge I. Alfaro , Fermın E.Gonzalez. Dendritic cell chimerism in oral mucosa of transplanted patients affected by graft-versus-host disease. J Oral Pathol Med. 2016 45(2):127- Carolina Ortiz, Claudia Lefimil, Paula I Rodas, Rolando Vernal, Mercedes Lopez, Claudio Acuña-Castillo, Monica Imarai, Alejandro Escobar. Neisseria gonorrhoeae modulates immunity by polarizing human macrophages to a M2 profile. Plos one 2015;10(6):e0130713. doi: 10.1371/journal.pone.0130713. ISI Díaz-Zúñiga J, Melgar-Rodríguez S, Alvarez C, Monasterio G, Benítez A, Ciuchi P, Díaz C, Mardones J, Escobar A, Sanz M, Vernal R. T-lymphocyte phenotype and function triggered by Aggregatibacter actinomycetemcomitans is serotype-dependent. J Periodontal Res. 2015 Mar 30. doi: 10.1111/jre.12270. Juan Pablo Aitken, Carolina Ortiz, Irene Morales, Gonzalo Rojas, Mauricio Baeza, Caroll Beltran, Alejandro Escobar. α-2-macroglobulin in saliva is associated with glycemic control in Patients with Type 2 diabetes mellitus. Disease Markers Volume 2015, Article ID 128653 http://dx.doi.org/10.1155/2015/128653. ISI Book chapters Alejandro Escobar & Juan Pablo Aitken. The Salivary Glands-Basics and Diagnostics. Chapter title: “Xerostomia an Update of Causes and Treatments”. 2019. Editorial Intech. Croacia. ISBN 978-953-51-5735-9. DOI: 10.5772/intechopen.72307 Mónica Imarai, Sebastián Reyes-Cerpa, Kevin Maisey, Alejandro Escobar, Claudio Acuña-Castillo. Sexually Transmitted Disease. Chapter title: Mucosal immunity and evasion strategies of Neisseria gonorrhoeae. 2012. Editorial Intech. Croacia. ISBN 978-593-51-0258-8. DOI: 10.5772/32824 Patent PCT/EP2008/062909 "An ex vivo fast and efficient process to obtain activated antigen presenting cells that are useful for therapies against cancer and immune system related diseases" Salazar, Flavio; Lopez, Mercedes; Pereda, Cristian; Aguilera, Raquel; Escobar, Alejandro. Others activities 2010 Diploma in Ethics of Biomedical Research. School of Medicine. Universidad de Chile. Santiago, Chile. 2018-present Chair of the Animal Ethics Committee Faculty of Dentistry. Universidad de Chile. 2019-present Board member Chilean Association of Immunology (ASOCHIN).