Research Area : Molecular targets
Position : Integrated members
Have extensive experience on the fields of nucleocytoplasmic transport, gene transcription, chromatin remodeling and apoptosis in both yeast and mammalian systems, and focused on yeast cellular and molecular biology and mammalian cell lines, using physiological, biochemical, molecular genetic and cellular approaches. Graduated in Biochemistry and performed undergraduate thesis work on the regulation of human cytochrome c1 transcription in mammalian cell lines. PhD thesis work focused on the regulation of protein transport between the nucleus and the cytoplasm in yeast cells. Later, studied DNA damage induced death in budding yeast. One of the genes involved in this response was Cks1. Later joined a major ongoing effort to study Cks proteins and their relation to cancer using both yeast and mammalian systems to study their role in chromatin remodeling. Now at CBMA, Universidade do Minho, using yeast as a tool in drug discovery and environmental monitoring.
Major societal challenges of the 21st century are Human Health and Wellbeing and the Pressure on Natural Resources. My goal, aligned with the CBMA strategic program and Horizon 2020, is to conduct cutting-edge research through a problem-oriented approach enabling breakthrough innovations, new tools and strategies impacting health promotion and environmental sustainability. I have established an independent research line studying proteasome-mediated modulation of cell death induced by chemotherapeutic agents, and collaborate with senior researchers in the apoptosis field, applied to cancer research. More recently, I started a CBMA effort focused on environmental monitoring and drug discovery.
TODOMICS- POCI-01-0145-FEDER-032059 "Omics approaches towards the industrial exploitation of Torulaspora delbrueckii: Elucidation of the molecular basis underlying complex cellular traits" (€ 234.357,87)
FunG-Eye PTDC/CTA-AMB/29505/2017 "A functional approach to unravel the interaction between fungicide pollution and fungi-mediated ecosystem processes"(€ 233,501.88)
Strategic Project UID/BIA/04050/2013: CENTRE OF MOLECULAR AND ENVIRONMENTAL BIOLOGY (€644.685,00)
Norte2020 project NORTE-01-0145-FEDER-000009 "EcoAgriFood: Innovative green products and processes to promote Agri-Food BioEconomy" (€ 931.842,42)
CBMA Project "Pestisense– Novel tools and data for the detection and assessment of ecological risks of pesticides"
Lance Armstrong Foundation project # 04 TCY19 "Identification of Molecular Determinants of Cisplatin Resistance" ($110,000)
PESSOA Project 3746/ 37989UA " Modulation of Bax activity and partner interaction by phosphoregulation"
FCT-ANR/BEX-BCM/0175/2012 "Phosphoregulation of Bax-dependent cell death" (€185,036)
PTDC/BBB-BQB/1850/2012 “Role of the yeast neutral sphingomyelinase in mitochondria function and iron homeostasis” (€156,127)
EXPL/BIM-ONC /0056/2012 “Regulation of Bax activation by the oncogene PKC epsilon: An approach to eliminate cancer cells” (€41,112)
PTDC/BIA-BCM/69448/2006 “Elucidation of ceramide-induced apoptosis: modulation of protein kinase C isoforms” (€150,000)
PTDC/AGR-ALI/102608/2008 “Mechanistic insights into acetic acid resistance in food spoilage yeasts: from the experimental model Saccharomyces cerevisiae to Zygosaccharomyces spp” (€193,648)
Completed official co-supervision of PhD theses, with FCT funding:
-António Rego, 2017: The role of ceramides in the mitochondrial apoptotic pathway induced by acetic acid FCT Ref SFRH/BD/79523/2011
-Helena Pereira, 2015: The role of the yeast ortholog of human Cathepsin D in the mitochondria-dependent vacuolar apoptotic pathway FCT Ref SFRH/BD/73139/2010
Completed official supervision of Masters theses as main supervisor:
-Carla Carvalho, 2018: Novel yeast biosensors for environmental monitoring
-Leslie Amaral, 2018: The role of metabolism in the sensitivity of Saccharomyces cerevisiae to the anti-cancer agent cisplatin
-Ana Rita Costa, 2018: The role of the DNA damage response in proteasome-mediated sensitivity to the anti-cancer agent cisplatin
-Nuno Machado, 2017: The mechanism underlying proteasome-mediated sensitivity to the chemotherapeutic agent cisplatin
-Filipa Mendes, 2017: Bax activation by PKCepsilon modulation
-Diana Silva, 2017: The role of mitochondrial effectors of cell death in isc1 mutants
-Vera Martins, 2015: Pathways regulating cisplatin-induced cell death in S. cerevisiae
-Soraia Pereira, 2015:Bax activation by PKCepsilon modulation: An approach to eliminate cancer cells
-Vanessa Campos, 2015: The role of mitochondrial effectors of cell death in isc1 mutants
-Elisabete Fernandes, 2014: Understanding the crosstalk between the mitochondria and the vacuole during acetic acid-induced apoptosis
-Rita Pacheco, 2013: Characterization of cell death induced by anti-tumor agents in S. cerevisiae
-Ana Duarte, 2013: Genome-wide identification of the genes involved in the positive and negative regulation of acetic acid-induced cell death
-Rita Cunha, 2013: The mechanism mediating nuclear translocation of the apoptosis inducing factor AIF
-Dulce Cunha, 2012: Characterization of cisplatin-induced cell death in S. cerevisiae
-Flávio Azevedo, 2011: The involvement of MAPK signaling pathways in acetic acid-induced cell death
Completed official supervision of Masters theses as co-supervisor:
-Jorge Macedo, 2019: Toxicity assessment of new products and processes for the agri-food sector potentially implicated in human wellbeing
-Vitória Baptista, 2018: Exploring yeast as a tool to study the regulation of the human pro-apoptotic protein Bax
Completed supervision of undergraduate theses:
-Nina Antunes, 2014: Characterization of protein kinases involved in the regulation of Bax
-Caterina Villa, 2012: Modulation of DNA damage-induced cell death in Saccharomyces cerevisiae by mammalian apoptosis regulators, p53 and BAX
27- Costa AR, Machado M, Rego A, Sousa MJ, Côrte-Real M and Chaves SR Proteasome inhibition inhibits cell death induced by the chemotherapeutic agent cisplatin downstream of DNA damage (2019) DNA Repair (Amst). Jan;73:28-33
26- Gomes S, Oliveira CSF, Azevedo-Silva J, Casanova MR, Barreto J, Pereira H, Chaves SR, Rodrigues LR, Casal M, Côrte-Real M, Baltazar F and Preto A: The Role of Diet Related Short-Chain Fatty Acids in Colorectal Cancer Metabolism and Survival: Prevention and Therapeutic Implications (2018) Curr Med Chem. May 29
25- Rego A, Cooper K, Snider J, Hannun Y, Costa V, Côrte-Real M and Chaves SR Acetic acid induces Sch9-dependent translocation of Isc1p from the endoplasmic reticulum into mitochondria (2018) Biochim Biophys Acta Mol Cell Biol Lipids. Jun;1863(6):576-583
24- Alves S, Neiri L, Chaves SR, Vieira S, Trindade D, Manon S, Dominguez V, Pintado B, Jonckheere V, Van Damme P, Silva RD, Aldabe R, Côrte-Real M. N-terminal acetylation modulates Bax targeting to mitochondria (2017) Int J Biochem Cell Biol. Dec 9;95:35-42
23- Barroca M, Rodrigues P, Sobral R, Costa MM, Chaves SR, Machado R, Casal M, Collins T. Antibiotic free selection for the high level biosynthesis of a silk-elastin-like protein (2016) Sci Rep. Dec 16;6:39329.
22- Trindade D, Pereira C, Chaves SR, Manon S, Côrte-Real M and Sousa MJ VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast (2016) Microbial Cell, Vol. 3, No. 10, pp. 369 - 379
21-Alves S, Castro L, Fernandes MS, Castro P, Priault M, Chaves SR, Moyer MP, Oliveira C, Seruca R, Côrte-Real M, Sousa MJ, Preto A Hotspot mutations in the KRAS oncogene function as positive regulators of autophagy (2015) Oncotarget. 13;6(31):30787-802.
20-Castro L, Alves S, Chaves SR, Costa JL, Soares P, Preto A RAF-1 promotes survival of thyroid cancer cells harboring RET/PTC1 rearrangement independently of ERK activation (2015) Mol Cell Endocrinol, pii: S0303-7207(15)30046-0.
19-Pereira H, Oliveira CSF, Castro L, Preto A, Chaves SR*, Côrte-Real M* (*equal contributor) Yeast as a tool to explore cathepsin D function (2015) Microbial Cell , Vol. 2, No. 7, pp. 225 - 234
18-Oliveira CSF, Pereira H, Alves S, Castro L, Baltazar F, Chaves SR, Preto A, Côrte-Real M Cathepsin D protects colorectal cancer cells from acetate-induced apoptosis through autophagy-independent degradation of damaged mitochondria (2015) Cell Death Dis. 2015 Jun 18;6:e1788.
17-Teixeira V, Medeiros TC, Vilaça R, Pereira AT, Chaves SR, Côrte-Real M, Moradas-Ferreira P, Costa V. Ceramide signalling impinges on Sit4p and Hog1p to promote mitochondrial fission and mitophagy in Isc1p-deficient cells (2015) Cell Signal 27(9):1840-9
16-Rego A, Duarte AM, Azevedo F, Sousa MJ, Côrte-Real M and Chaves SR Cell wall dynamics modulate acetic acid-induced apoptotic cell death of Saccharomyces cerevisiae (2014) Microbial Cell 1(9):303-14
15-Rego A, Trindade D, Chaves SR, Manon S, Costa V, Sousa MJ, Côrte-Real M Insigths from the yeast model system towards the understanding of apoptosis regulation by sphingolipids (2014) FEMS Yeast Research 14 (1), pp. 160-178
14-Sousa M, Duarte AM, Chaves SR, Pacheco A, Leão C, Côrte-Real M, Sousa MJ Genome-wide identification of genes involved in the positive and negative regulation of acetic acid-induced programmed cell death in Saccharomyces cerevisiae (2013) BMC Genomics 14 (1), 838
13-Pacheco A, Azevedo F, Rego A, Santos J, Chaves SR, Côrte-Real M and Sousa MJ C2-phytoceramide perturbs lipid rafts and cell integrity in Saccharomyces cerevisiae in a sterol-dependent manner (2013) PloS one 8 (9), e74240
12-Cunha D., Cunha R., Côrte-Real M. and Chaves S.R. Cisplatin-induced cell death in Saccharomyces cerevisiae is programmed and rescued by proteasome inhibition DNA Repair (Amst). (2013) Jun 1;12(6):444-9.
11-Marques C., Oliveira C.S., Alves S., Chaves S.R., Coutinho O.P., Côrte-Real M., Preto A. Acetate-induced apoptosis in colorectal carcinoma cells involves lysosomal membrane permeabilization and cathepsin D release Cell Death Dis. (2013) Feb 21;4:e507.
10-Pereira HP, Azevedo F Sousa MJ, Chaves SR and Côrte-Real M. The protective role of yeast cathepsin D in acetic acid-induced apoptosis depends on ANT (Aac2p) but not on the voltage-dependent channel (Por1p) FEBS Letters (2013) 587(2):200-5
9-Rego A., Costa A.M., Chaves S.R., Pereira H.P., Sousa M.J., Moradas-Ferreira P., Costa V. and Côrte-Real M. Modulation of mitochondrial outer membrane permeabilization and apoptosis by ceramide metabolism. PLoS ONE (2012) 7(11): e48571.
8-Barbosa AD, Graça J, Mendes V, Chaves SR, Amorim MA, Mendes MV, Moradas-Ferreira P, Côrte-Real M, Costa V. Activation of the Hog1p kinase in Isc1p-deficient yeast cells is associated with mitochondrial dysfunction, oxidative stress sensitivity and premature aging. Mech Ageing Dev. (2012) 133(5):317-30.
7-Sousa MJ, Azevedo F, Pedras A, Marques C, Coutinho OP, Preto A, Gerós H, Chaves SR, Côrte-Real M. Vacuole-mitochondrial cross-talk during apoptosis in yeast: a model for understanding lysosome-mitochondria-mediated apoptosis in mammals. Biochem Soc Trans. (2011) Oct;39(5):1533-7
6-Chaves SR*, Rosenblum JS Efficient Nuclear Transport of Structurally Disturbed Cargo: Mutations in a Cargo Protein Switch Its Cognate Karyopherin. PLoS ONE (2011) 6(2): e16846. (*Corresponding author)
5-Vilela-Moura A., Schuller D., Mendes-Faia A., Silva R.D., Chaves S.R., Sousa M.J. and Côrte-Real M. The impact of acetate metabolism on yeast fermentative performance and wine quality: zymological reduction of volatile acidity of grape-musts and wines Appl Microbiol Biotechnol. (2011) Jan;89(2):271-80.
4-Chaves S, Baskerville C, Yu V, Reed SI. Cks1, Cdk1 and the 19S proteasome collaborate to regulate gene-induction-dependent nucleosome eviction in yeast. Mol Cell Biol. (2010) Nov;30(22):5284-94 (Evaluated and recommended by the Faculty of 1000 (Post-publication peer review)).
3-Pereira C, Chaves S, Alves S, Salin B, Camougrand N, Manon S, Sousa MJ, Côrte-Real M. Mitochondrial degradation in acetic acid-induced yeast apoptosis: the role of Pep4 and the ADP/ATP carrier Mol Microbiol. (2010) Jun;76(6):1398-410 (Commented at Molecular Microbiology, Micro Commentary by Lawen A. Another piece of the puzzle of apoptotic cytochrome c release, 66(3):553-6)
2-Martinsson Ahlzén H.S, Liberal V., Grünenfelder B., Chaves S.R., Spruck C.H. and Reed S.I. Cyclin-dependent kinase associated proteins Cks1 and Cks2 are essential during early embryogenesis and for cell cycle progression in somatic cells. Mol Cell Biol. (2008) 28(18):5698-709
1-Chaves S.R. and Blobel G. Nuclear import of Spo12p, a protein essential for meiosis. J Biol Chem. (2001) 276(21), pp: 17712-7