ROGER CHAMMAS
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina - Docente
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- The PANcreatic Disease ReseArch (PANDoRA) consortium: Ten years' experience of association studies to understand the genetic architecture of pancreatic cancer(2023) CAMPA, Daniele; GENTILUOMO, Manuel; STEIN, Angelika; AOKI, Mateus Nobrega; OLIVERIUS, Martin; VODICKOVA, Ludmila; JAMROZIAK, Krzysztof; THEODOROPOULOS, George; PASQUALI, Claudio; GREENHALF, William; ARCIDIACONO, Paolo Giorgio; UZUNOGLU, Faik; PEZZILLI, Raffaele; LUCHINI, Claudio; PUZZONO, Marta; LOOS, Martin; GIACCHERINI, Matteo; KATZKE, Verena; MAMBRINI, Andrea; KIUDELIENE, Edita; FEDERICO, Kauffmann Emanuele; JOHANSEN, Julia; HUSSEIN, Tamas; MOHELNIKOVA-DUCHONOVA, Beatrice; EIJCK, Casper H. J. van; BRENNER, Hermann; FARINELLA, Riccardo; PEREZ, Juan Sainz; LOVECEK, Martin; BUECHLER, Markus W.; HLAVAC, Viktor; IZBICKI, Jakob R.; HACKERT, Thilo; CHAMMAS, Roger; ZERBI, Alessandro; LAWLOR, Rita; FELICI, Alessio; GOETZ, Mara; CAPURSO, Gabriele; GINOCCHI, Laura; GAZOULI, Maria; KUPCINSKAS, Juozas; CAVESTRO, Giulia Martina; VODICKA, Pavel; MOZ, Stefania; NEOPTOLEMOS, John P.; KUNOVSKY, Lumir; BOJESEN, Stig E.; CARRARA, Silvia; GIOFFREDA, Domenica; MORKUNAS, Egidijus; ABIAN, Olga; BUNDUC, Stefania; BASSO, Daniela; BOGGI, Ugo; WLODARCZYK, Barbara; SZENTESI, Andrea; VANELLA, Giuseppe; CHEN, Inna; BIJLSMA, Maarten F.; KIUDELIS, Vytautas; LANDI, Stefano; Ben Schoettker; CORRADI, Chiara; GIESE, Nathalia; KAAKS, Rudolf; PEDUZZI, Giulia; HEGYI, Peter; MORELLI, Luca; FURBETTA, Niccolo; SOUCEK, Pavel; LATIANO, Anna; TALAR-WOJNAROWSKA, Renata; LINDGAARD, Sidsel C.; DIJK, Frederik; MILANETTOJ, Anna Caterina; TAVANO, Francesca; CERVENA, Klara; EROSS, Balint; TESTONI, Sabrina G.; VERHAGEN-OLDENAMPSEN, Judith H. E.; MALECKA-WOJCIESKO, E.; COSTELLO, Eithne; SALVIA, Roberto; MAIELLO, Evaristo; ERMINI, Stefano; SPERTI, Cosimo; HOLLECZEK, Bernd; PERRI, Francesco; SKIECEVICIENE, Jurgita; ARCHIBUGI, Livia; LUCCHESI, Maurizio; RIZZATO, Cosmeri; CANZIAN, FedericoPancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33 susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease. Additionally, the inability to adequately power research questions prevents small monocentric studies from being successful. Several consortia have been established to pursue a better understanding of the genetic architecture of pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groups. In the last ten years, PANDoRA has contributed to the discovery of 25 susceptibility loci, a feat that will be instrumental in stratifying the population by risk and optimizing preventive strategies.
- Presence of human breast cancer xenograft changes the diurnal profile of amino acids in mice(2022) PAULA JR., Rubens; SONEHARA, Nathalia Martins; JARDIM-PERASSI, Bruna Victorasso; PAL, Akos; ASAD, Yasmin; CHUFFA, Luiz Gustavo Almeida; CHAMMAS, Roger; RAYNAUD, Florence I.; ZUCCARI, Debora A. P. C.Human xenografts are extremely useful models to study the biology of human cancers and the effects of novel potential therapies. Deregulation of metabolism, including changes in amino acids (AAs), is a common characteristic of many human neoplasms. Plasma AAs undergo daily variations, driven by circadian endogenous and exogenous factors. We compared AAs concentration in triple negative breast cancer MDA-MB-231 cells and MCF10A non-tumorigenic immortalized breast epithelial cells. We also measured plasma AAs in mice bearing xenograft MDA-MB-231 and compared their levels with non-tumor-bearing control animals over 24 h. In vitro studies revealed that most of AAs were significantly different in MDA-MB-231 cells when compared with MCF10A. Plasma concentrations of 15 AAs were higher in cancer cells, two were lower and four were observed to shift across 24 h. In the in vivo setting, analysis showed that 12 out of 20 AAs varied significantly between tumor-bearing and non-tumor bearing mice. Noticeably, these metabolites peaked in the dark phase in non-tumor bearing mice, which corresponds to the active time of these animals. Conversely, in tumor-bearing mice, the peak time occurred during the light phase. In the early period of the light phase, these AAs were significantly higher in tumor-bearing animals, yet significantly lower in the middle of the light phase when compared with controls. This pilot study highlights the importance of well controlled experiments in studies involving plasma AAs in human breast cancer xenografts, in addition to emphasizing the need for more precise examination of exometabolomic changes using multiple time points.
- O-glycan sialylation alters galectin-3 subcellular localization and decreases chemotherapy sensitivity in gastric cancer(2016) SANTOS, Sofia N.; JUNQUEIRA, Mara S.; FRANCISCO, Guilherme; VILANOVA, Manuel; MAGALHAES, Ana; BARUFFI, Marcelo Dias; CHAMMAS, Roger; HARRIS, Adrian L.; REIS, Celso A.; BERNARDES, Emerson S.ST6GalNAc-I, the sialyltransferase responsible for sialyl-Tn (sTn) synthesis, has been previously reported to be positively associated with cancer aggressiveness. Here we describe a novel sTn-dependent mechanism for chemotherapeutic resistance. We show that sTn protects cancer cells against chemotherapeutic-induced cell death by decreasing the interaction of cell surface glycan receptors with galectin-3 and increasing its intracellular accumulation. Moreover, exogenously added galectin-3 potentiated the chemotherapeutics-induced cytotoxicity in sTn non-expressing cells, while sTn overexpressing cells were protected. We also found that the expression of sTn was associated with a reduction in galectin-3-binding sites in human gastric samples tumors. ST6GalNAc-I knockdown restored galectin-3-binding sites on the cell surface and chemotherapeutics sensibility. Our results clearly demonstrate that an interruption of O-glycans extension caused by ST6GalNAc-I enzymatic activity leads to tumor cells resistance to chemotherapeutic drugs, highlighting the need for the development of novel strategies to target galectin-3 and/or ST6GalNAc-I.
conferenceObject Stochastic model of contact inhibition and the proliferation of melanoma in situ.(2018) MORAIS, Mauro Cesar C.; STUHL, Izabella; SABINO, Alan U.; LAUTENSCHLAGER, Willian W.; QUEIROGA, Alexandre S.; TORTELLI JR., Tharcisio C.; CHAMMAS, Roger; SUHOV, Yuri; RAMOS, Alexandre F.- Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk(2021) LU, Ye; GENTILUOMO, Manuel; MACAUDA, Angelica; GIOFFREDA, Domenica; GAZOULI, Maria; PETRONE, Maria C.; KELEMEN, Dezso; GINOCCHI, Laura; MORELLI, Luca; PAPIRIS, Konstantinos; GREENHALF, William; IZBICKI, Jakob R.; KIUDELIS, Vytautas; MOHELNIKOVA-DUCHONOVA, Beatrice; BUENO-DE-MESQUITA, Bas; VODICKA, Pavel; BRENNER, Hermann; DIENER, Markus K.; PEZZILLI, Raffaele; IVANAUSKAS, Audrius; SALVIA, Roberto; SZENTESI, Andrea; AOKI, Mateus Nobrega; NEMETH, Balazs C.; SPERTI, Cosimo; JAMROZIAK, Krzysztof; CHAMMAS, Roger; OLIVERIUS, Martin; ARCHIBUGI, Livia; ERMINI, Stefano; NOVAK, Janos; KUPCINSKAS, Juozas; STROUHAL, Ondrej; SOUCEK, Pavel; CAVESTRO, Giulia M.; MILANETTO, Anna C.; VANELLA, Giuseppe; NEOPTOLEMOS, John P.; THEODOROPOULOS, George E.; LAARHOVEN, Hanneke W. M. van; MAMBRINI, Andrea; MOZ, Stefania; KALA, Zdenek; LOVECEK, Martin; BASSO, Daniela; UZUNOGLU, Faik G.; HACKERT, Thilo; TESTONI, Sabrina G. G.; HLAVAC, Viktor; ANDRIULLI, Angelo; LUCCHESI, Maurizio; TAVANO, Francesca; CARRARA, Silvia; HEGYI, Peter; ARCIDIACONO, Paolo G.; BUSCH, Olivier R.; LAWLOR, Rita T.; PUZZONO, Marta; BOGGI, Ugo; GUO, Feng; MALECKA-PANAS, Ewa; CAPURSO, Gabriele; LANDI, Stefano; TALAR-WOJNAROWSKA, Renata; STROBEL, Oliver; GAO, Xin; VASHIST, Yogesh; CAMPA, Daniele; CANZIAN, FedericoAlthough 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p<10(-5)) compared with the additive effects (p>10(-3)), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5x10(-8)). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.
- Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk(2021) LU, Ye; CORRADI, Chiara; GENTILUOMO, Manuel; MATURANA, Evangelina Lopez de; THEODOROPOULOS, George E.; ROTH, Susanne; MAIELLO, Evaristo; MORELLI, Luca; ARCHIBUGI, Livia; IZBICKI, Jakob R.; SARLOS, Patricia; KIUDELIS, Vytautas; OLIVERIUS, Martin; AOKI, Mateus Nobrega; VASHIST, Yogesh; EIJCK, Casper H. J. van; GAZOULI, Maria; TALAR-WOJNAROWSKA, Renata; MAMBRINI, Andrea; PEZZILLI, Raffaele; BUENO-DE-MESQUITA, Bas; HEGYI, Peter; SOUCEK, Pavel; NEOPTOLEMOS, John P.; FRANCO, Gregorio Di; SPERTI, Cosimo; KAUFFMANN, Emanuele F.; HLAVAC, Viktor; UZUNOGLU, Faik G.; ERMINI, Stefano; MALECKA-PANAS, Ewa; LUCCHESI, Maurizio; VANELLA, Giuseppe; DIJK, Frederike; MOHELNIKOVA-DUCHONOVA, Beatrice; BAMBI, Franco; PETRONE, Maria Chiara; JAMROZIAK, Krzysztof; GUO, Feng; KOLAROVA, Katerina; CAPRETTI, Giovanni; MILANETTO, Anna Caterina; GINOCCHI, Laura; LOVECEK, Martin; PUZZONO, Marta; LAARHOVEN, Hanneke W. M. van; CARRARA, Silvia; IVANAUSKAS, Audrius; PAPIRIS, Konstantinos; BASSO, Daniela; ARCIDIACONO, Paolo G.; IZBEKI, Ferenc; CHAMMAS, Roger; VODICKA, Pavel; HACKERT, Thilo; PASQUALI, Claudio; PIREDDA, Maria L.; COSTELLO-GOLDRING, Eithne; CAVESTRO, Giulia Martina; SZENTESI, Andrea; TAVANO, Francesca; WLODARCZYK, Barbara; BRENNER, Hermann; KREIVENAITE, Edita; GAO, Xin; BUNDUC, Stefania; VERMEULEN, Roel C. H.; SCHNEIDER, Martin A.; LATIANO, Anna; GIOFFREDA, Domenica; TESTONI, Sabrina G. G.; KUPCINSKAS, Juozas; LAWLOR, Rita T.; CAPURSO, Gabriele; MALATS, Nuria; CAMPA, Daniele; CANZIAN, FedericoGenetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case-Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07-1.17, p = 3.03 x 10(-6) in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.
- Stochastic model of contact inhibition and the proliferation of melanoma in situ(2017) MORAIS, Mauro Cesar Cafundo; STUHL, Izabella; SABINO, Alan U.; LAUTENSCHLAGER, Willian W.; QUEIROGA, Alexandre S.; TORTELLI JR., Tharcisio Citrangulo; CHAMMAS, Roger; SUHOV, Yuri; RAMOS, Alexandre F.Contact inhibition is a central feature orchestrating cell proliferation in culture experiments; its loss is associated with malignant transformation and tumorigenesis. We performed a co-culture experiment with human metastatic melanoma cell line (SKMEL-147) and immortalized keratinocyte cells (HaCaT). After 8 days a spatial pattern was detected, characterized by the formation of clusters of melanoma cells surrounded by keratinocytes constraining their proliferation. In addition, we observed that the proportion of melanoma cells within the total population has increased. To explain our results we propose a spatial stochastic model (following a philosophy of the Widom-Rowlinson model from Statistical Physics and Molecular Chemistry) which considers cell proliferation, death, migration, and cell-to-cell interaction through contact inhibition. Our numerical simulations demonstrate that loss of contact inhibition is a sufficient mechanism, appropriate for an explanation of the increase in the proportion of tumor cells and generation of spatial patterns established in the conducted experiments.
- Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells(2017) LERNER, Leticia K.; FRANCISCO, Guilherme; SOLTYS, Daniela T.; ROCHA, Clarissa R. R.; QUINET, Annabel; VESSONI, Alexandre T.; CASTRO, Ligia P.; DAVID, Taynah I. P.; BUSTOS, Silvina O.; STRAUSS, Bryan E.; GOTTIFREDI, Vanesa; STARY, Anne; SARASIN, Alain; CHAMMAS, Roger; MENCK, Carlos F. M.Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells afterUV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53-and Pol H-silenced cells. Viability increase was associated with improved elongation of nascent DNA, indicating the protective effect was due to more efficient lesion bypass by pol eta. This protection was observed in cells proficient or deficient in nucleotide excision repair, suggesting that, from a cell survival perspective, proper bypass of DNA damage can be as relevant as removal. These results indicate p53 controls the induction of pol eta in DNA damaged human cells, resulting in improved TLS and enhancing cell tolerance to DNA damage, which parallels SOS responses in bacteria.
- Community-based network analyses reveal emerging connectivity patterns of protein-protein interactions in murine melanoma secretome(2021) FRANCISQUINI, Rodrigo; BERTON, Rafael; SOARES, Sandro Gomes; PESSOTTI, Dayelle S.; CAMACHO, Mauricio F.; ANDRADE-SILVA, Debora; BARCICK, Uilla; SERRANO, Solange M. T.; CHAMMAS, Roger; NASCIMENTO, Maria C. V.; ZELANIS, AndreProtein-protein interaction networks (PPINs) are static representations of protein connections in which topological features such as subgraphs (communities) may contain proteins functionally related, revealing an additional layer of interactome complexity. We created two PPINs from the secretomes of a paired set of murine melanocytes (a normal melanocyte and its transformed phenotype). Community structures, identified by a graph clustering algorithm, resulted in the identification of subgraphs in both networks. Interestingly, the underlying structure of such communities revealed shared and exclusive proteins (core and exclusive nodes, respectively), in addition to proteins that changed their location within each community (rewired nodes). Functional enrichment analysis of core nodes revealed conserved biological functions in both networks whereas exclusive and rewired nodes in the tumoral phenotype network were enriched in cancer-related processes, including TGF beta signaling. We found a remarkable shift in the tumoral interactome, resulting in an emerging pattern which was driven by the presence of exclusive nodes and may represent functional network motifs. Our findings suggest that the rearrangement in the tumoral interactome may be correlated with the malignant transformation of melanocytes associated with substrate adhesion impediment. The interactions found in core and new/rewired nodes might potentially be targeted for therapeutic intervention in melanoma treatment. Significance: Malignant transformation is a result of synergistic action of multiple molecular factors in which genetic alterations as well as protein expression play paramount roles. During oncogenesis, cellular crosstalk through the secretion of soluble mediators modulates the phenotype of transformed cells which ultimately enables them to successfully disrupt important signaling pathways, including those related to cell growth and proliferation. Therefore, in this work we profiled the secretomes of a paired set of normal and transformed phenotypes of a murine melanocyte. After assembling the two interactomes, clusters of functionally related proteins (network communities) were observed as well as emerging patterns of network rewiring which may represent an interactome signature of transformed cells. In summary, the significance of this study relies on the understanding of the repertoire of 'normal' and 'tumoral' secretomes and, more importantly, the set of interacting proteins (the interactome) in both of these conditions, which may reveal key components that might be potentially targeted for therapeutic intervention.