Viola-r.qxd 26/1/2011 12:03 ÌÌ ™ÂÏ›‰·1 INTERNATIONAL JOURNAL OF ONCOLOGY 38: 591-592, 2011 1 Cover legend: João P.B. Viola; a member of The Editorial Academy of The International Journal of Oncology NFAT1. Dr Viola and colleagues demonstrated that NFAT- deficient mice consistently showed a marked increase in their immune response; likewise, CD4+ T cells from NFAT1-/- mice displayed an enhanced Th2 immunity, as evidenced by an overexpression of IL-4. These data suggested for the first time that the NFAT1 transcription factor might have a negative role in regulating T cell proliferation and cytokine gene expression during the immune response. His studies were very well received, resulting in publications in Science, Immunity and Blood. He also took on a much more biochemical project while he was at Dr Rao's laboratory, mapping the in vivo phosphorylation sites of the NFAT1 transcription factor in resting and activated T cells. This work still stands as the best example of how to identify all the functionally relevant phosphorylation sites of a heavily phosphorylated protein. It João P.B. Viola is a Senior Scientist at the National Cancer was incorporated into two papers, published in Journal of Institute (INCA), Rio de Janeiro, Brazil. The long-term interest Biological Chemistry and Molecular Cell, which described the of Dr Viola's laboratory is to study the cellular and molecular biochemical mechanisms of NFAT1 regulation by phospho- mechanisms of inducible gene transcription in cell activation rylation and calcineurin-mediated dephosphorylation. and transformation. The main area of investigation is focused As an independent investigator at the Brazilian National on studying the role of NFAT (Nuclear Factor of Activated Cancer Institute, Dr Viola focused his studies on better under- T cells) transcription factors in cell cycle progression, cell standing the molecular mechanisms of the NFAT proteins in differentiation and apoptosis, and their relation to malignant lymphocyte proliferation and cell cycle regulation. His group disorders. Dr Viola received his M.D. degree in 1989 from demonstrated for the first time that NFAT target genes include the School of Medical Sciences, State University of Rio de genes encoding cell cycle-associated proteins such as cyclins, Janeiro (UERJ); and a Ph.D. degree in Biophysics in 1998 observations published in FASEB J (Caetano et al, FASEB J from the Federal University of Rio de Janeiro (UFRJ), Brazil. 16: 1940, 2002). Dr Viola's group also demonstrated that During the pursue of his Ph.D. degree, Dr Viola moved to NFAT1 transcription factor represses cyclin A2 expression in Boston (USA) and performed his research under the super- lymphocytes, and may act as a silencer of gene transcription vision of Dr Anjana Rao. He was appointed Research Associate during cell cycle progression (Carvalho et al, Cell Cycle 6: at the Division of Cellular and Molecular Biology at the Dana- 1789, 2007). More recently, his group demonstrated that Farber Cancer Institute (1994-1996) and at the Center for ectopic expression of NFAT1 and NFAT2 in fibroblasts Blood Research (1996-1997), Harvard Medical School, where produced opposite phenotypes in the regulation of cell cycle he conducted studies on molecular mechanisms of T cell progression, apoptosis, and cell transformation. In fact, NFAT2 activation. João Viola returned to Brazil to join the National acts as a positive regulator of cell proliferation, a repressor of Cancer Institute as Junior Investigator at the Division of cell death, and an inducer of cell transformation. Conversely, Experimental Medicine in 1998, where he started his NFAT1 overexpression enhanced cell death, repressed the independent research group. In 2000, Dr Viola was appointed cell cycle, and subverted cell transformation. These results Associate Investigator and moved his laboratory within the raise the hypothesis that NFAT1 and NFAT2 may function as National Cancer Institute, to the Division of Cellular Biology, tumor suppressor or oncogene, respectively (Robbs et al, Mol where he is currently conducting his studies. In 2009 he was Cell Biol 28: 7168, 2008). Regardless of their widely known appointed Senior Investigator and Head of the Program of cytokine gene expression properties, Dr Viola's laboratory Cellular Biology. and others demonstrated that NFAT transcription factors During his period at Dr Rao's laboratory, he played a regulate other genes related to cell cycle progression, cell major role in two separate projects. In a more integrative differentiation and apoptosis; unraveling a broader role for venue, Dr Viola participated in the generation of a transgenic these proteins in normal cell physiology. These findings model to study the role of NFAT family members in the support the idea that NFAT proteins may act as a central mammalian immune system in vivo by investigating the regulator of the cell homeostasis, thereby determining the immune phenotype of mice lacking the transcription factor overall outcome of tumor development. Viola-r.qxd 26/1/2011 12:03 ÌÌ ™ÂÏ›‰·2 INTERNATIONAL JOURNAL OF ONCOLOGY 38: 591-592, 2011 Another line of research Dr Viola holds special interest both by Brazilian and international institutions. Dr Viola has for is gene regulation during T cell activation and differen- received scholarship awards from the Brazilian National tiation. Upon T cell stimulation, CD4+ T lymphocytes may Council for Research (CNPq) as Junior Investigator in undergo a Th differentiation that is mostly characterized by the Immunology (1999-2004) and as Senior Investigator in distinct pattern of cytokines they secrete. Th1 cells produce Immunology (2004-present). He was also honored as State IFN-Á, which is essential for the eradication of intracellular Scientist in 2007 and 2009 by the Rio de Janeiro State pathogens and in immunity against tumors. Several factors Foundation for Research (FAPERJ). João Viola is a member can influence the differentiation pathway of CD4+ T helper of the Brazilian Society of Immunology (SBI), Brazilian cells, specially the cytokines prevailing within the micro- Society of Cell Biology (SBBC), Brazilian Society of Bio- environment where these cells encounter antigens. IL-12 and chemistry and Molecular Biology, The American Association IFN-Á are known to be the major Th1-inducing cytokines. Dr of Immunologists (AAI) and The American Society for Viola's group has addressed the involvement of NFAT1 Microbiology (ASM). During the term of 2002-2003, Dr transcription factor in the regulation of IFN-Á production in Viola was elected first secretary of the Brazilian Society in CD8+ T cells and its influence on Th1 immune responses. They Immunology. He was actively involved in the organization of show that IFN-Á production by CD8+ T cells is dependent on several scientific meetings and congresses, including the XIII NFAT1 transcription factor and may be an essential regulator International Congress of Immunology (2007) where he was of Th immune responses in vivo (Teixeira et al, J Immunol at the advisory scientific board and the Meeting in Signaling 175: 5931, 2005). in Cell Death, Cancer and the Immune System (2010) where Continuing a long-standing collaboration with Dr Patricia he was part of the organizing committee (Amarante-Mendes Bozza, at the Oswaldo Cruz Foundation (Brazil), Dr Viola is et al, Cell Death Differ 17: 1368, 2010). Dr Viola is a member also carrying studies on the functional significance of lipid of the Editorial Board of Cancer Immunology Immunotherapy droplets to cancer, focusing in the roles of lipid droplets bio- (2006-present) and the Editorial Academy of the International genesis during colon cancer development. Increased lipo- Journal of Oncology (2008-present). He also acts as consultant genesis has emerged as a common phenotype to numerous for several research funding agencies and scientific Journals, human carcinomas and has been associated to poor prognosis including International Journal of Cancer, Oncogene, The in breast, prostate and colon cancer. Altered lipid metabolism FASEB Journal, The Journal of Immunology, The Journal of in cancer cells involves modulation of multiple lipogenic Pathology, Molecular Biology of the Cell and Nature Review enzymes. Lipid droplets are emerging as dynamic organelles in Cancer. In addition, he devotes great attention to science involved in lipid metabolism and inflammation. Dr Viola's education, serving as Chair of the Program of Research group and colleagues demonstrated that lipid droplets in colon Fellowship in Oncology and the Institutional Program of cancer cells are dynamic and functional active organelles Scientific Initiation of the Brazilian National Cancer Institute centrally involved in prostaglandin synthesis and may (2009-present), and also as a member of the Board of the potentially have implications to the pathogenesis of adeno- Ph.D. Program in Oncology of the Brazilian National Cancer carcinoma of colon (Accioly et al, Cancer Res 15: 1732, 2008). Institute (2007-present). Dr Viola has mentored the work of The impact of Dr Viola's research studies and contributions 15 graduate students (M.Sc. and Ph.D.) and 3 post-doctoral to the field along his scientific career have been recognized fellows..