DNA Damage Response and Repair

We investigate the cellular mechanisms that detect, signal, and repair DNA damage to maintain genome stability. Our focus includes DNA double-strand breaks repair pathways such as homologous recombination and non-homologous end joining. We explore the role of chromatin structure and dynamics in coordinating the repair process and their involvement in preventing genomic instability.

R-loops and Transcription-Associated Genome Instability

We study how R-loops, RNA-DNA hybrid structures that form during transcription, contribute to genome instability. Our research focuses on understanding the mechanisms involved in R-loop regulation and how their dysregulation leads to transcription-associated DNA damage. We aim to uncover the molecular pathways that cells use to resolve R-loop-induced genome instability.

Transcription Regulation and pre-mRNA Processing

We explore how the transcription cycle is tightly coupled with pre-mRNA processing events such as splicing. By studying key regulatory splicing mechanisms, we aim to understand how defects in transcription and mRNA processing contribute to transcriptional stress and genome instability.

Genomic Instability in Cancer

We investigate how genomic instability drives cancer progression, focusing on mutations in DNA repair genes and chromatin regulators. Our work aims to reveal how defects in the DNA damage response, coupled with transcription and replication stress, contribute to tumorigenesis. Additionally, we explore the potential for targeting genomic instability with anti-cancer therapies that exploit vulnerabilities in cancer cell DNA repair pathways.

2024: TessellateBio. Coordinator: Sérgio de Almeida. Funding Agency: Tessellate Bio BV

2023/2024: New horizons for Rett syndrome: exploring the role of transposable elements using genetically engineered human stem cell models. Coordinator: Anne-Valerie Gendrel. Funding Agency: Fundação para a Ciência e a Tecnologia.

2023/2024: Investigating R-loops as important regulators of splicing. Coordinator: Robert Manfred Martin. Funding Agency: Fundação para a Ciência e a Tecnologia.

2021/2024: O Papel da Transcrição Induzida por Quebras do DNA no Envelhecimento   – Decoding the Role of DNA Break-Induced Transcription in Ageing. Coordinator: Sérgio de Almeida. Funding Agency: Fundação para a Ciência e a Tecnologia.

R.M. Martin, M.R. de Almeida, E. Gameiro, S.F. de Almeida (2023). Live-cell imaging unveils distinct R-loop populations with heterogeneous dynamics. Nucleic Acids Research, Oct 11: gkad812. https://doi.org/10.1093/nar/gkad812.

J.C. Sabino, M.R. de Almeida, P.L. Abreu, A.M. Ferreira, M.M. Domingues, N.C. Santos, C.M. Azzalin, A.R. Grosso, S.F. de Almeida (2022). Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops. eLife 11: e69476. https://doi.org/10.7554/eLife.69476.

E.R. Gomes, S.F. de Almeida (2021). TREX1-dependent DNA damage links nuclear rupture to tumor cell invasion. Developmental Cell 56(22): 3040-3041. https://doi.org/10.1016/j.devcel.2021.11.003.

A.C. Vítor, S.C. Sridhara, J.C. Sabino, A.I. Afonso, A.R. Grosso, R.M. Martin, S.F. de Almeida (2019). Single-molecule imaging of transcription at damaged chromatin. Science Advances 5(1): eaau1249. https://doi.org/10.1126/sciadv.aau1249.

S.C. Sridhara, S. Carvalho, A.R. Grosso, L.M. Gallego-Paez, M. Carmo-Fonseca, S.F. de Almeida (2017). Transcription dynamics prevent RNA-mediated genomic instability through SRPK2-dependent DDX23 phosphorylation. Cell Reports. https://doi.org/10.1016/j.celrep.2016.12.050.

A.R. Grosso, A.P. Leite, S. Carvalho, M.R. Matos, F.B. Martins, A.C. Vítor, J.M. Desterro, M. Carmo-Fonseca, S.F. de Almeida (2015). Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma. eLife 4: e09214. https://doi.org/10.7554/eLife.09214.

2015 Portuguese Society of Human Genetics Award

2011 Pfizer Award for Basic Research

2006 LabMed Science Award