João Gonçalves

Molecular Microbiology and Biotechnology

To tackle disease unmet needs the Molecular Microbiology and Biotechnology laboratory aims to develop new strategies of antibody engineering and synthetic biology for the advance of new biopharmaceuticals by interrogating the immune humoral and cellular responses in infectious diseases and biologic therapies.

Understand the immune response in infectious diseases and biologic therapies.

Our research interrogates how the antibody and cellular responses occur during Covid19 infection and vaccination, and during patient treatment with biologic therapies. We aim to determine what is the impact of immune profiling, dynamics, and depth of immunogenic outcomes for a successful control of infection and anti-drug antibody response.

Mimic nature with synthetic biology.

We aim to develop novel methodologies to generate genetic diversity directly into antibody genes using genome edition by CRISPR, TALE or zinc-finger nucleases and couple it with cellular display/selection. These technologies are explored together with synthetic biology to design novel genetic circuits into cell and phages and generate improved methods to discover therapeutic antibodies.

Integration of antibody engineering and synthetic biology for oncology and infectious diseases.

We are interested to integrate antibody engineering with synthetic biology to develop bispecific and multi-functional domain antibodies and conditional CAR-T cells. The boolean logic gates-based regulation of gene expression in CAR-T by conditional extracellular signals aims to improve pharmacologic activities in oncology and viral diseases, such as solid tumors and HIV-cure.

Vale FF, Vítor J, Marques AT, Azevedo-Pereira JM, Anes E, Goncalves J. Origin, phylogeny, variability and epitope conservation of SARS-CoV-2 worldwide. Virus Res. 2021; 304, 198526. DOI: 10.1016/j.virusres.2021.198526.
Perdigão P, Cunha-Santos C, Barbas CF, Santa-Marta M, Gonçalves J. Protein delivery of cell-penetrating zinc-finger activators stimulates latent HIV-1-infected cells. Mol Ther Methods Clin Dev. 2020; 18, 145–158. DOI: 10.1016/j.omtm.2020.05.016.
Ministro JH, Oliveira SS, Oliveira JG, Cardoso M, Aires-da-Silva F, Corte-Real S, Gonçalves J. Synthetic antibody discovery against native antigens by CRISPR/Cas9-library generation and endoplasmic reticulum screening. Appl Microbiol Biotechnol. 2020; 104(6), 2501– 2512. DOI: 10.1007/s00253-020-10423-3.
Cunha-Santos C, Perdigão P, Martin F, Oliveira JG, Cardoso M, Manuel A, Taveira N, Gonçalves J. Inhibition of HIV replication through siRNA carried by CXCR4-targeted chimeric nanobody. Cell Mol Life Sci. 2020; 77(14), 2859–2870. DOI: 10.1007/s00018-019-03334-8.
Goncalves J, Santos M, Acurcio R, Iria I, Gouveia L, Matos Brito P, Catarina Cunha-Santos A, Barbas A, Galvão J, Barbosa I, Aires da Silva F, Alcobia A, Cavaco M, Cardoso M, Delgado Alves J, Carey JJ, Dörner T, Eurico Fonseca J, Palmela C, Torres J, … Danese S. Antigenic response to CT-P13 and infliximab originator in inflammatory bowel disease patients shows similar epitope recognition. Aliment Pharmacol Ther. 2018; 48(5), 507–522. DOI: 10.1111/apt.14808.

João Gonçalves

Group Leader


Phone: (+351) 217946486

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Faculdade de Farmácia da Universidade de Lisboa | Av. Professor Gama Pinto
1649-003 Lisboa | Portugal

Phone | +351 217 946 400
Fax | +351 217 946 470
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