NAME: Mauro Martins Teixeira
eRA COMMONS USER NAME (credential, e.g., agency login): MTEIXEIRA_UFMG
POSITION TITLE: Professor of Biochemistry and Immunology
INSTITUTION AND LOCATION
FIELD OF STUDY
Faculdade de Medicina da UFMG, Brazil
Hospital das Clinicas de Belo Horizonte, Brazil
National Heart and Lung Institute, University of London
London School of Tropical Medicine and Hygiene
A. Personal Statement
I am an MD PhD with certification in Internal Medicine (Brazil) and Infectious Diseases (DTMH, Royal Society). I work at the Federal University of Minas Gerais (UFMG) since 1997 where I head a large group of scientists interested in the study of various aspects of the inflammatory response in the context of infection and sterile inflammation. My group is leading inflammation research center in Brazil. In the context of infection, our studies have provided convincing evidence that the inflammatory contributes to disease during host x microbial interactions and aspects of the inflammatory response can be targeted for the development of novel inflammation-based therapies to treat infection. For the last 10 years and because of the local relevance of these infections, I have coordinated the National Institute of Science and Technology in dengue and host-microbial interactions and, more recently, participated intensely in the National effort to define Zika research priorities. My clinical interest is mostly related to infectious diseases of local relevance, in particular, arboviral and protozoan infections.
B. Positions and Honors
Positions and Employment
1995-1997 Post Doctoral Research Fellow, National Heart and Lung Institute, University of London
1997-2000 Associate Professor, Department of Pharmacology, Universidade Federal de Minas Gerais (UFMG)
2000-2005 Associate Professor, Department of Biochemistry and Immunology, UFMG
2005-present Professor, Department of Biochemistry and Immunology, UFMG
Other Experience and Professional Memberships
Member of Editorial Board: Pharmacology and Therapeutics (2005-2015), Inflammation Research (2012- present), Frontiers in Immunology (2012-present), Frontiers in Pharmacology (2012-present); British Journal of Pharmacology (Senior Editor, From 12/2017)
2013- Vice-president of the Brazilian Academy of Science (MG and Center-East)
2014- Member of the Scientific Advisory Board of Anvisa (the Brazilian counterpart of the FDA)
2012-2014 President Brazilian Society of Pharmacology
2016- Member of the Board of Immunopharmacology Section of IUPHAR
2018- President – IUIS Immunopharmacology committee
2018- President Brazilian Society of Inflammation (2018-2020)
2009 Medal of The National Order of Scientific Merit, Brazilian Government
2009 Elected Member of the Brazilian Academy of Science
2012 Elected Member of TWAS (the World Academy of Sciences)
C. Contribution to Science
Complete List of Published Work (585 items) in MyBibliography at PubMed:
1. Determination of mechanisms of eosinophil recruitment in vivo and demonstration of the inhibitory effects of cyclicAMP-elevating agents in the controlling eosinophil influx. These studies were initiated during my PhD. Using animal models of direct eosinophil trafficking to the skin of guinea pigs or mice, we provided the initial framework for understanding mechanisms (both chemoattractants, cell adhesion molecules and intracellular pathways) involved in the recruitment of eosinophils in vivo. Subsequent studies evaluated the concept of tissue priming and cooperation between mediators for eosinophil trafficking. Altogether these studies served as bases and provided the mechanisms for the development and understanding of the in vivo inhibitory actions of drugs which elevate cyclic AMP on eosinophil influx. We also participated in the discovery and potential effects of evasins, chemokine binding proteins derived from ticks, on the influx of leukocytes in vivo. These were important contributions to the understanding of leukocyte trafficking in vivo and how one can use such knowledge to develop novel anti-inflammatory strategies, including Cyclic AMP elevating agents (such as phosphodiesterase 4 inhibitors) and chemokine-binding proteins.
a) Teixeira MM, Giembycz MA, Lindsay MA, Hellewell PG. Pertussis toxin shows distinct early signalling events in platelet-activating factor-, leukotriene B4-, and C5a-induced eosinophil homotypic aggregation in vitro and recruitment in vivo. Blood. 1997 Jun 15;89(12):4566-73.
b) Teixeira MM, Wells TN, Lukacs NW, Proudfoot AE, Kunkel SL, Williams TJ, Hellewell PG. Chemokine-induced eosinophil recruitment. Evidence of a role for endogenous eotaxin in an in vivo allergy model in mouse skin. J Clin Invest. 1997 Oct 1;100(7):1657-66.
c) Klein A, Talvani A, Silva PM, Martins MA, Wells TN, Proudfoot A, Luckacs NW, Teixeira MM. Stem cell factor-induced leukotriene B4 production cooperates with eotaxin to mediate the recruitment of eosinophils during allergic pleurisy in mice. J Immunol. 2001 Jul 1;167(1):524-31.
d) Vieira AT, Fagundes CT, Alessandri AL, Castor MG, Guabiraba R, Borges VO, Silveira KD, Vieira EL, Gonçalves JL, Silva TA, Deruaz M, Proudfoot AE, Sousa LP, Teixeira MM. Treatment with a novel chemokine-binding protein or eosinophil lineage-ablation protects mice from experimental colitis. Am J Pathol. 2009 Dec;175(6):2382-91.
2. Definition of the role of the microbiota in driving acute responses. Very early on my return to Brazil, we established a range of animal models to study sterile inflammation, in an attempt to compare inflammatory responses in sterile inflammation to that caused by infection. We found several molecules important for the process of ischemia and reperfusion injury. During teses studies, we discovered a previously unrecognized role of the microbiota in driving acute inflammatory responses. We found some of the mechanisms involved in this process and the relevance of the microbiota for other signs of inflammation, including pain and fever. These studies were unique and preceded much of the current knowledge of the interaction of the microbiota with the immune system.
a) Souza DG, Vieira AT, Soares AC, Pinho V, Nicoli JR, Vieira LQ, Teixeira MM. The essential role of the intestinal microbiota in facilitating acute inflammatory responses. J Immunol. 2004 Sep 15;173(6):4137-46
b) Souza DG, Fagundes CT, Amaral FA, Cisalpino D, Sousa LP, Vieira AT, Pinho V, Nicoli JR, Vieira LQ, Fierro IM, Teixeira MM. The required role of endogenously produced lipoxin A4 and annexin-1 for the production of IL-10 and inflammatory hyporesponsiveness in mice. J Immunol. 2007;179(12):8533-43.
c) Amaral FA, Sachs D, Costa VV, Fagundes CT, Cisalpino D, Cunha TM, Ferreira SH, Cunha FQ, Silva TA, Nicoli JR, Vieira LQ, Souza DG, Teixeira MM. Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2193-7.
d) Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009 Oct 29;461(7268):1282-6.
3) Definition of mechanisms involved in leukocyte recruitment in models of sterile inflammation. In addition to providing relevant contributions on the role of the microbiota in driving sterile inflammation, we have conducted a series of relevant studies dissecting mechanisms involved in sterile tissue injury. In particular, we have contributed significantly to defining novel mechanisms and anti-inflammatory pathways involved in mediating ischemia and reperfusion injury, including the role of bradykinin receptors, PAFR, CXCR1/2, angiotensin receptors and the cross talk between TNF-a and IL-10 in reperfusion injury. Subsequent studies in collaboration with a company (Dompe) helped developing a novel class of CXCR1/2 (reparexin and derived molecules) and novel C5aR allosteric antagonists. My group has also defined a previously unrecognized role of DNA release from hepatocytes in mediating tissue injury caused by paracethamol.
a) Souza DG, Guabiraba R, Pinho V, Bristow A, Poole S, Teixeira MM. IL-1-driven endogenous IL-10 production protects against the systemic and local acute inflammatory response following intestinal reperfusion injury. J Immunol. 2003 May 1;170(9):4759-66
b) Souza DG, Bertini R, Vieira AT, Cunha FQ, Poole S, Allegretti M, Colotta F, Teixeira MM. Repertaxin, a novel inhibitor of rat CXCR2 function, inhibits inflammatory responses that follow intestinal ischaemia and reperfusion injury. Br J Pharmacol. 2004 Sep;143(1):132-42.
c) Moriconi A, Cunha TM, Souza GR, Lopes AH, Cunha FQ, Carneiro VL, Pinto LG, Brandolini L, Aramini A, Bizzarri C, Bianchini G, Beccari AR, Fanton M, Bruno A, Costantino G, Bertini R, Galliera E, Locati M, Ferreira SH, Teixeira MM, Allegretti M. Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief. Proc Natl Acad Sci U S A. 2014;111(47):16937-42
d) Marques PE, Oliveira AG, Pereira RV, David BA, Gomides LF, Saraiva AM, Pires DA, Novaes JT, Patricio DO, Cisalpino D, Menezes-Garcia Z, Leevy WM, Chapman SE, Mahecha G, Marques RE, Guabiraba R, Martins VP, Souza DG, Mansur DS, Teixeira MM, Leite MF, Menezes GB. Hepatic DNA deposition drives drug-induced liver injury and inflammation in mice. Hepatology. 2015 Jan;61(1):348-60
3) Contribution to understanding the role of chemokines in the context of protozoan and helminth infections of humans. Upon my return to Brazil in 1997, I started a series of experiments trying to dissect the contribution of chemokines and their receptors in the context of infectious diseases. An important aspect of these studies was their translational nature as we attempted to carry out experiments in vitro, in experimental models and in patients. At that time, the diversity of chemokines and their receptors was just being characterized and it was necessary to understand their contribution to the pathogenesis of infectious diseases. Focusing on the so-called inflammatory chemokines and especially on chemokines active on CCR1, CCR2, CCR3 and CCR5, we showed the expression of these molecules in the context of acute T cruzi and schistosoma infection in mice and their major contribution to the pathogenesis of tissue fibrosis and dysfunction. In the context of disease, levels of chemokines and expression of receptors on leukocytes associated with disease severity and response to treatment. These were among the first studies describing the relevance of chemokines for protozoan and helminth infections of humans.
a) Falcão PL, Correa-Oliveira R, Fraga LA, Talvani A, Proudfoot AE, Wells TN, Williams TJ, Jose PJ, Teixeira MM. Plasma concentrations and role of macrophage inflammatory protein-1alpha during chronic Schistosoma mansoni infection in humans. J Infect Dis. 2002 Dec 1;186(11):1696-700.
b) Marino AP, da Silva A, dos Santos P, Pinto LM, Gazzinelli RT, Teixeira MM, Lannes-Vieira J. Regulated on activation, normal T cell expressed and secreted (RANTES) antagonist (Met-RANTES) controls the early phase of Trypanosoma cruzi-elicited myocarditis. Circulation. 2004 Sep 14;110(11):1443-9.
c) Talvani A, Rocha MO, Barcelos LS, Gomes YM, Ribeiro AL, Teixeira MM. Elevated concentrations of CCL2 and tumor necrosis factor-alpha in chagasic cardiomyopathy. Clin Infect Dis. 2004 Apr 1;38(7):943-50.
d) Souza AL, Roffê E, Pinho V, Souza DG, Silva AF, Russo RC, Guabiraba R, Pereira CA, Carvalho FM, Barsante MM, Correa-Oliveira R, Fraga LA, Negrão-Correa D, Teixeira MM. Potential role of the chemokine macrophage inflammatory protein 1alpha in human and experimental schistosomiasis. Infect Immun. 2005 Apr;73(4):2515-23.
4) Characterized novel mediators and pathways of the resolution of inflammation. In the last 10 years or so, it has become clear that the resolution of inflammation is a very active process dependent on the production of mediators (known as mediators of anti-inflammation), much akin to the need of an active effort to mount an inflammatory response. It is believed that failure to resolve inflammation may contribute significantly to chronic inflammatory diseases (and also to infection) and that administration of pro-resolving molecules or drugs that mimic their action may have significant anti-inflammatory actions. In the last few years, the literature has seen much effort in trying to define the range of mediators of resolution of inflammation and the relevance of these mediators in the context of disease. We have provided several important discoveries to the field, more specifically the discovery of crucial novel pathways involved in the resolution of inflammation, including the role of PI3K-gamma for leukocyte survival in vivo and discovery of the pro-resolving effects of reactive oxygen species (H2O2) annexin-A1, angiotensin-(1-7) and GILZ in vivo.
a) Pinho V, Souza DG, Barsante MM, Hamer FP, De Freitas MS, Rossi AG, Teixeira MM. Phosphoinositide-3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation. J Leukoc Biol. 2005 May;77(5):800-10.
b) Sousa LP, Lopes F, Silva DM, Tavares LP, Vieira AT, Rezende BM, Carmo AF, Russo RC, Garcia CC, Bonjardim CA, Alessandri AL, Rossi AG, Pinho V, Teixeira MM. PDE4 inhibition drives resolution of neutrophilic inflammation by inducing apoptosis in a PKA-PI3K/Akt-dependent and NF-kappaB-independent manner. J Leukoc Biol. 2010 May;87(5):895-904
c) Sugimoto MA, Ribeiro ALC, Costa BRC, Vago JP, Lima KM, Carneiro FS, Ortiz MMO, Lima GLN, Carmo AAF, Rocha RM, Perez DA, Reis AC, Pinho V, Miles LA, Garcia CC, Teixeira MM, Sousa LP Plasmin and plasminogen induce macrophage reprogramming and regulate key steps of inflammation resolution via annexin A1. Blood. 2017 May 25;129(21):2896-2907.
d) Barroso LC, Magalhaes GS, Galvão I, Reis AC, Souza DG, Sousa LP, Santos RAS, Campagnole-Santos MJ, Pinho V, Teixeira MM. Angiotensin-(1-7) Promotes Resolution of Neutrophilic Inflammation in a Model of Antigen-Induced Arthritis in Mice. Front Immunol. 2017 Nov 20;8:1596.
5) Provided proof-of-concept studies showing that there are mediators that are preferentially associated with disease in the context of infection and that treating inflammation may be beneficial in the context of certain infections. Upon encounter with a potential pathogen, leukocytes and tissue resident cells present in the potential host release a series of mediators of inflammation. These mediators of the inflammatory response are needed for the host to mount an effective innate and adaptive immune response against the pathogen. However, inadequate (decreased, enhanced, altered or misplaced) production of mediators of inflammation may contribute to development of disease. We have been working with the hypothesis that it may be possible to differentiate mediators of inflammation crucial for disease development from those necessary for the immune response against the host. If these are indeed different, it may be possible to generate drugs that prevent disease in the context of infection.
a) Souza DG, Fagundes CT, Sousa LP, Amaral FA, Souza RS, Souza AL, Kroon EG, Sachs D, Cunha FQ, Bukin E, Atrasheuskaya A, Ignatyev G, Teixeira MM. Essential role of platelet-activating factor receptor in the pathogenesis of Dengue virus infection. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):14138-43.
b) Fagundes CT, Costa VV, Cisalpino D, Amaral FA, Souza PR, Souza RS, Ryffel B, Vieira LQ, Silva TA, Atrasheuskaya A, Ignatyev G, Sousa LP, Souza DG, Teixeira MM. IFN-γ production depends on IL-12 and IL-18 combined action and mediates host resistance to dengue virus infection in a nitric oxide-dependent manner. PLoS Negl Trop Dis. 2011 Dec;5(12):e1449.
c) Garcia CC, Russo RC, Guabiraba R, Fagundes CT, Polidoro RB, Tavares LP, Salgado AP, Cassali GD, Sousa LP, Machado AV, Teixeira MM. Platelet-activating factor receptor plays a role in lung injury and death caused by Influenza A in mice. PLoS Pathog. 2010 Nov 4;6(11):e1001171
d) Jackman JA, Costa VV, Park S, Real ALCV, Park JH, Cardozo PL, Ferhan AR, Olmo IG, Moreira TP, Bambirra JL, Queiroz VF, Queiroz-Junior CM, Foureaux G, Souza DG, Ribeiro FM, Yoon BK, Wynendaele E, De Spiegeleer B, Teixeira MM, Cho NJ. Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide. Nat Mater. 2018 Nov;17(11):971-977
D. Major Research Support:
Major ONGOING RESEARCH PROJECTS (US$ 1 = BRLd$3.7 as of February 2019):
CNPq/FAPEMIG 465425/2014-3 Teixeira (PI) 01/01/2017-12/31/2023
Instituto Nacional de Ciencia e Tecnologia (INCT) in Dengue and host-microbial interactions. This is a major national program grant focused on generating science to deal with dengue and the new arboviral infections (Zika and Chikungunya). (BRL$ 7,500,000)
CNPq/FAPEMIG-UK/MRC Newton Fund MR/N017544/1 Teixeira (co-PI) 01/01/2016-12/31/2019
Resolution of Inflammation in Dengue
Aim to study the relevance of mediators of the resolution of the inflammatory response in the context of human and experimental dengue infection (BP$ 400,000)
Dompe Pharmaceuticals-Italy Teixeira (co-PI) 01/01/2011-12/31/2019
Novel antagonists at 7-TM receptors
Aim to develop the clinical pharmacology of allosteric inhibitors at chemokine (CXCR1/2) and Complement (C5aR) receptors. US$250,000
CNPq/FINEP/CAPES 440423/2016/3 Teixeira (PI) 01/2017-10-2020
Neuroprotection and zika infection
Aim to develop animal models and to examine the role of mediators of neurodegeration in the context of Zika infection (BRL 1,500,000)
Fundação Buntantan Teixeira (site PI) 07/2016 – 02/2024
Phase III Clincal study to evaluate the efficacy of an attenuated Dengue I, 2, 3 and 4 vaccine developed by Butantan
One of the linical research sites responsible for testing a Dengue Vaccine Clinical Candidate (enrolment of 1,079 individuals ended Feburary 2019)
Role: Site PI