Drug Response & Resistance



António Sebastião Rodrigues




Campus Sant’Ana
Ed. CEDOC II, room 2.24
Pólo de Investigação NMS-UNL
Rua Câmara Pestana, nº 6
1150-082 Lisboa, Portugal
Email: sebastiao.rodrigues_at_nms.unl.pt
Phone: +351 218 803 100 Ext 26050
Fax: + 351 218 803 010

Main Interests:

Drug response at the cellular level, and its role in determining the outcome of therapy. Particular emphasis is placed on the molecular mechanisms which are associated with the ability to resist therapeutic agents, specifically microRNAs that mediate breast cancer tumorigenesis and susceptibility to breast cancer drugs (J.Rueff, B.Gomes). Moreover, the ability of microRNAs and natural compounds to revert this resistance to cancer drugs through interaction with ABC transporters and gene methylation patterns, thus acting as chemosensitizers, may help create a better prognostic marker set to predict the clinical outcome of patients and optimize pharmacotherapy (J.Rueff, C.Martins; A. Armada; M.Viveiros).
A further interest is the role of functional variants of Na/glucose transporters (SGLT2) in the pharmacodynamics of SGLT2 inhibitors. This can have a major impact in the use of SGLT2 inhibitors as oral anti-diabetic drugs in type 2 diabetes mellitus (J.Calado).
The use of next generation omics is a major future focus, in collaboration with the Proteomics group (D.Penque) and Next Generation Sequencing group (L.Vieira), and will leverage our research and allow the identification of targeted mechanisms involved in drug response and resistance.

Research areas

Involvement of microRNAs in the DNA damage response in breast cancer

Natural compounds as chemosensitizers of cancer drug therapy

Impact of functional SGLT2 variants in the pharmacodynamics of SGLT2 inhibitors

Running as PI:

MicroRNA involvement in breast cancer susceptibility and progression

Running as Collaborator (2004-2017)

• Terry Fox Grant 2017. Liga Portuguesa Contra o Cancro. “Breast Cancer: clinical significance of variants of unknown significance (VUSs) in homologous recombination repair genes – from sequencing to functional analysis in familial breast cancer patients”

Terry Fox Grant 2017. Liga Portuguesa Contra o Cancro. “Breast Cancer: clinical significance of variants of unknown significance (VUSs) in homologous recombination repair genes – from sequencing to functional analysis in familial breast cancer patients”

HYBRID XXI -Desenvolvimento de novas formulações de produtos fitofarmacêuticos com microorganismos ou compostos de origem natural (algas) associado a substâncias ativas químicas. LISBOA-01-0247-FEDER-011130. Programa Operacional Regional de Lisboa Horizonte 2020. SAPEC.

Mechanisms of Resistance to Imatinib in Chronic Myeloid Leukemia. PTDC/SAU-GMG/71720/2006

Chemical, Radiochemical and Biological Studies of Pyrazolyl-Alkylamine Pt(II) Complexes: Application on the Development of Novel Anti-cancer Drugs. PTDC/QUI/66813/2006

Multicomponent Technetium and Gallium metallointercallators for targeted Radiotherapy. POCTI/QUI/57632/2004

Chapters in international books:

C. Martins, J. Rueff, A.S. Rodrigues
Food Microbiology series
Taylor and Francis CRC Press (2017, ‘in press’)

A. S. Rodrigues, B. C. Gomes, C. Martins, M. Gromicho, N. G. Oliveira, P. S. Guerreiro, J. Rueff. DNA Repair and Resistance to Cancer Therapy.
In C. Chen (Ed.) “New Research Directions in DNA Repair”, ISBN: 978-953-51-1114-6; pp 489-528. InTech ( 2013)

M. Monteiro, A. S. Rodrigues, A. Vicente, J. Murias, C. Martins, J. Rueff, H. Borba, Medimond: Potassium bromate oxidative DNA damage in repair proficient and deficient CHO cell lines. 01/2007: pages 93-97; , ISBN: 9788875874032 (2007)

Medeiros, M.G.; Rodrigues, A.S.;Batoréu, M.C.C.; Laires, A.; Rueff, J.; Zhitkovich, A.
Biomarkers of Chromium Exposure and Cytogenetic damage.
in “Leather Tanning and Welding Industry Workers”. Plenum Press; New York. 01/2003; (2003)

J. Gaspar, I. Duarte Silva, A. Laires, A. Rodrigues, S. Costa, J. Rueff.
Prooxidant activities of flavonols: a structure activity study.
in: Kumpulainen J.T. and Salonen J.T. (eds), Natural Antioxidants and Lipid Peroxidation in Atherosclerosis and Cancer. pp: 291-297.The Royal Society of Chemistry, Cambridge, UK. (1996).

A. S. Rodrigues, I. D. Silva, M. J. Monteiro, H. Caria, A. Laires, T. Chaveca, J. Rueff: Activation of Promutagens by Rat CYP P450 Expressing V79 Cells. 01/1994: pages 205-208; ISBN: 274200050X (1994)

J. Rueff, A. Laires, A. Brás, H. Borba, T. Chaveca, J. Gaspar, A. Rodrigues, L. Cristóvão e M. Monteiro.
DNA damage and oxygen Species.
in Lambert M. (ed), “DNA Repair Mechanisms and their Biological Implications in Mammalian Cells” pp.171-181. Plenum Press, New York. (1989).

International Journal Publications (2017-2012)

D’ Oliveira Martins F(1), Gomes BC, Rodrigues AS, Rueff
Genetic Susceptibility in Acute Pancreatitis: Genotyping of GSTM1, GSTT1, GSTP1,
CASP7, CASP8, CASP9, CASP10, LTA, TNFRSF1B, and TP53 Gene Variants.
Pancreas. 2017 ;46(1):71-76

Michael J. Coady, Abdulah El Tarazi, René Santer, Pierre Bissonnette, Louis J. Sasseville, Joaquim Calado, Yoann Lussier, Christopher Dumayne, Daniel G. Bichet, and Jean-Yves Lapointe, 2016.
“MAP17 Is a Necessary Activator of Renal Na+/Glucose Cotransporter SGLT2”
Journal of the American Society of Nephrology 28: ccc–ccc.

Gomes, B.C., Martins, M., Lopes, P., Morujão, I., Oliveira, M., Araújo, A., Rueff, J. and Rodrigues, A.S., 2016. Prognostic value of microRNA-203a expression in breast cancer. Oncology Reports, 36(3), pp.1748-1756.

Martins, M., Baptista, P.V., Mendo, A.S., Correia, C., Videira, P., Rodrigues, A.S., Muthukumaran, J., Santos-Silva, T., Silva, A., da Silva, M.F.C.G. and Gigante, J., 2016. In vitro and in vivo biological characterization of the anti-proliferative potential of a cyclic trinuclear organotin (IV) complex. Molecular BioSystems, 12(3), pp.1015-1023.

-The human chromosomal fragile sites more often involved in constitutional deletions and duplications – A genetic and statistical assessment. Gomes DP, Sequeira IJ, Figueiredo C, Rueff J and Brás A. AIP Conference Proceedings 2016,1790, 080003

Gonçalves, J., Moreira, E., Sequeira, I.J., Rodrigues, A.S., Rueff, J. and Brás, A., 2016. Integration of HIV in the Human Genome: Which Sites Are Preferential? A Genetic and Statistical Assessment. International Journal of Genomics, 2016. doi:10.1155/2016/2168590

Armada, A., Martins, C., Spengler, G., Molnar, J., Amaral, L., Rodrigues, A.S. and Viveiros, M., 2016. Fluorimetric Methods for Analysis of Permeability, Drug Transport Kinetics, and Inhibition of the ABCB1 Membrane Transporter. Cancer Drug Resistance: Overviews and Methods, pp.87-103.

Rueff, J. and Rodrigues, A.S., 2016. Cancer Drug Resistance: A Brief Overview from a Genetic Viewpoint. Cancer Drug Resistance: Overviews and Methods, pp.1-18.

Gromicho, M., Rueff, J. and Rodrigues, A.S., 2016. Dynamics of Expression of Drug Transporters: Methods for Appraisal. Cancer Drug Resistance: Overviews and Methods, pp.75-85.

Gomes, B.C., Santos, B., Rueff, J. and Rodrigues, A.S., 2016. Methods for Studying MicroRNA Expression and Their Targets in Formalin-Fixed, Paraffin-Embedded (FFPE) Breast Cancer Tissues. Cancer Drug Resistance: Overviews and Methods, pp.189-205.

Gomes, B.C., Rueff, J. and Rodrigues, A.S., 2016. MicroRNAs and cancer drug resistance. Cancer Drug Resistance: Overviews and Methods, pp.137-162.

Costa, E.M., Silva, S., Costa, M.R., Pereira, M., Campos, D.A., Odila, J., Madureira, A.R., Cardelle-Cobas, A., Tavaria, F.K., Rodrigues, A.S. and Pintado, M.M., 2014. Chitosan mouthwash: Toxicity and in vivo validation. Carbohydrate polymers, 111, pp.385-392.

Luís, D.V., Silva, J., Tomaz, A.I., de Almeida, R.F., Larguinho, M., Baptista, P.V., Martins, L.M., Silva, T.F., Borralho, P.M., Rodrigues, C.M. and Rodrigues, A.S., 2014. Insights into the mechanisms underlying the antiproliferative potential of a Co (II) coordination compound bearing 1, 10-phenanthroline-5, 6-dione: DNA and protein interaction studies. JBIC Journal of Biological Inorganic Chemistry, 19(6), pp.787-803.

Martins, C., Doran, C., Silva, I.C., Miranda, C., Rueff, J. and Rodrigues, A.S., 2014. Myristicin from nutmeg induces apoptosis via the mitochondrial pathway and down regulates genes of the DNA damage response pathways in human leukaemia K562 cells. Chemico-biological interactions, 218, pp.1-9.

Gromicho, M., Magalhães, M., Torres, F., Dinis, J., Fernandes, A.R., Rendeiro, P., Tavares, P., Laires, A., Rueff, J. and Sebastião Rodrigues, A., 2013. Instability of mRNA expression signatures of drug transporters in chronic myeloid leukemia patients resistant to imatinib. Oncology reports, 29(2), pp.741-750.

Genetic and statistical study of HIV integration in the human genome. Sequeira IJ, Gonçalves J, Moreira E, Mexia JT, Rueff J, and Brás A. AIP Conference Proceedings 2013, 1558, 813-816

Predominance of constitutional chromosomal rearrangements in human chromosomal fragile sites. Sequeira IJ, Mexia JT, Santiago J, Mamede R, Silva E, Santos J, Faria D, Rueff J and Brás A. Open Journal of Genetics 2013, 3, 8-13

Louro, A., Peralta, L., Soares, S., Pereira, A., Cunha, G., Belchior, A., Ferreira, L., Gil, O.M., Louro, H., Pinto, P. and Rodrigues, A.S., 2013. Human exposure to indoor radon: a survey in the region of Guarda, Portugal. Radiation protection dosimetry, 154(2), pp.237-244.

Dinis, J., Silva, V., Gromicho, M., Martins, C., Laires, A., Tavares, P., Rendeiro, P., Torres, F., Rueff, J. and Rodrigues, A., 2012. DNA damage response in imatinib resistant chronic myeloid leukemia K562 cells. Leukemia & lymphoma, 53(10), pp.2004-2014.

Martins, C., Cação, R., Cole, K.J., Phillips, D.H., Laires, A., Rueff, J. and Rodrigues, A.S., 2012. Estragole: a weak direct-acting food-borne genotoxin and potential carcinogen. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 747(1), pp.86-92.

S Rodrigues, A., Dinis, J., Gromicho, M., Martins, C., Laires, A. and Rueff, J., 2012. Genomics and cancer drug resistance. Current pharmaceutical biotechnology, 13(5), pp.651-673.

Sousa, C., Fernandes, F., Valentão, P., Rodrigues, A.S., Coelho, M., Teixeira, J.P., Silva, S., Ferreres, F., de Pinho, P.G. and Andrade, P.B., 2012. Brassica oleracea L. var. costata DC and Pieris brassicae L. aqueous extracts reduce methyl methanesulfonate-induced DNA damage in V79 hamster lung fibroblasts. Journal of agricultural and food chemistry, 60(21), pp.5380-5387.

Miguel Viveiros, Instituto de Higiene e Medicina Tropical (IHMT), UNL

Fátima Nogueira, Instituto de Higiene e Medicina Tropical (IHMT), UNL

CGC Genetics / Centro de Genética Clínica

Manuela Martins, Unidade de Anatomia patológica, Centro Hospitalar Lisboa Central

Unidade Funcional de Patologia mamária, Centro Hospitalar Lisboa Central

AstraZeneca/BMS (SGLT2 inhibitors for the treatment of type 2 diabetes mellitus)

Centro Hospitalar Lisboa Central – Serviço de Nefrologia

Michael Coady, Groupe d’étude des protéines membranaires (GÉPROM), Université de Montréal

René Santer, UnivKinderklinik, Hamburg

David Polidori, Janssen Research and Development, San Diego.

Marc Fila, Service de Néphrologie Pédiatrique, Hopital Robert Debré.

Centro de Matematica Aplicada (CMA), Department of Mathematics, Faculty of Sciences and Technology, UNL

SAPEC, contract for industry, consultant.