Dr. Manuel A.F.V. Gonçalves

Research:

I am a molecular biologist whose main research activities have been developing viral vector systems for the permanent or transient genetic modification of human cells and investigating high-fidelity genome editing procedures. Currently, my research interests are focused on; (i) converting viral vectors into delivery agents of gene-editing tools (i.e., programmable DNA-cleaving enzymes and exogenous DNA-repairing templates); (ii) studying the impact of epigenetic mechanisms on the performance of different gene-editing tools and strategies; and (iii) developing seamless and scarless gene-editing approaches based on recruiting and guiding specific DNA repair pathways after the delivery of programmable nucleases or “nickases” into target cells. The resulting toolboxes and findings are directed towards modelling and correcting genetic defects in pluripotent and hematopoietic stem cells as well as in muscle progenitor cells from patients with Duchenne muscular dystrophy, a frequent X-linked muscle-wasting disorder.

Curriculum Vitae:

I received my M.Sc. degree in Plant biotechnology from the University of Lisbon, Portugal. After a post-graduation period in a gene therapy company, I was awarded a fellowship from the Portuguese Foundation for Science and Technology to perform my Ph.D. research on the development of viral vector systems for the stable genetic modification of human cells. This research took place at the University of Leiden and at the biotechnology company Crucell (Johnson & Johnson’s group), in the Netherlands. In 2015, I became associate professor at the Department of Molecular Cell Biology of the Leiden University Medical Center (currently Department of Cell and Chemical Biology). In this capacity, I supervise a research team investigating genome editing strategies based on repairing targeted double-stranded or single-stranded DNA breaks with exogenous (donor) DNA templates. This research aims at achieving seamless and scarless genetic modification of human stem/progenitor cells for disease modelling and correction.

Publication links:
https://orcid.org/0000-0002-8111-1073
https://www.ncbi.nlm.nih.gov/pubmed/?term=goncalves+ma+leiden

Publications

  • In trans paired nicking triggers seamless genome editing without double-stranded DNA cutting.

    Chen X, Janssen JM, Liu J, Maggio I, 't Jong AEJ, Mikkers HMM, Gonçalves MA.

    Nat. Commun. 8: 657 (2017). doi: 10.1038/s41467-017-00687-1.

  • Probing the impact of chromatin conformation on genome editing tools.

    Chen X, Rinsma M, Janssen JM, Liu J, Maggio I, Gonçalves MA.

    Nucleic Acids Res. 2016 44: 6482-6492 (2016). doi: 10.1093/nar/gkw524.

  • Adenoviral vector DNA for accurate genome editing with engineered nucleases.

    Holkers M, Maggio I, Henriques SF, Janssen JM, Cathomen T, Gonçalves MA

    Nat. Methods 11: 1051-1057 (2014). doi: 10.1038/nmeth.3075.

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