Sérgio de Almeida Lab

Chromatin & Epigenetics

Our research focuses on the mechanisms that control chromatin dynamics during transcription and DNA damage repair and how they coordinate with the processes that safeguard the genome integrity. Our general aims are twofold: first, we aim at investigating molecular aspects of the different stages of the transcription cycle, focusing on pre-mRNA processing and chromatin modification events; in addition, we study the molecular mechanisms that sense, signal and repair DNA damage.

To this end, we employ a multidisciplinary research strategy that combines experimental tools and approaches from areas such as cell and molecular biology, biochemistry, live-cell microscopy, next-generation sequencing and bioinformatics. A major focus of our research is to understand how changes in transcription, pre-mRNA processing, chromatin modification and DNA damage response are linked to the development of human diseases such as cancer.

Research Team

Research Areas

• Chromatin dynamics during transcription and DNA damage response
• Epigenetic mechanisms for genome and transcriptome integrity
• Mechanisms of DNA damage sensing and repair
• Cancer epigenomics

Ongoing Research Projects

2018/2021 O papel determinante que lesões no DNA desempenham na transcrição e o seu impacto na diferenciação celular e em cancro. Coordinator: Sérgio de Almeida. Funding Agency: Fundação para a Ciência e a Tecnologia.

2018/2021 Papel fisiológico de inativação seletiva de núcleos em células multinucleadas. Coordinator: Robert Martin. Funding Agency: Fundação para a Ciência e a Tecnologia.

Awards

2015 Portuguese Society of Human Genetics Award

2013 Selected as Associate Lab of the EpiGeneSys Network

2011 Pfizer Award for Basic Research

2006 LabMed Science Award

2005 Pulido Valente Science Award (Honors)

Selected Publications

For our complete publications list click here

• Sabino JC, de Almeida MR, Abreu PL, Ferreira AM, Domingues MM, Santos NC, Azzalin CM, Grosso AR, de Almeida SF. “Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops” eLife, 2022 Feb 22;11:e69476. doi: 10.7554/eLife.69476.
• Gomes ER, de Almeida SF. “TREX1-dependent DNA damage links nuclear rupture to tumor cell invasion” Developmental Cell, 2021 Nov 22;56(22):3040-3041. doi: 10.1016/j.devcel.2021.11.003.
• Vítor AC, Sridhara SC, Sabino JC, Afonso AI, Grosso AR, Martin RM, de Almeida SF. "Single-molecule imaging of transcription at damaged chromatin" Science Advances. 2019 Jan 9;5(1):eaau1249. doi:10.1126/sciadv.aau1249.
• Bonnet A, Grosso AR, Elkaoutari A, Coleno E, Presle A, Sridhara SC, Janbon G, Géli V, de Almeida SF, Palancade B "Introns Protect Eukaryotic Genomes from Transcription-Associated Genetic Instability" Molecular Cell 2017 Aug 17;67(4):608-621.e6 doi:10.1016/j.molcel.2017.07.002
• Sridhara SC, Carvalho S, Grosso AR, Gallego-Paez LM, Carmo-Fonseca M, de Almeida SF "Transcription dynamics prevent RNA-mediated genomic instability through SRPK2-dependent DDX23 phosphorylation" Cell Reports. 2017 Jan 10. doi: 10.1016/j.celrep.2016.12.050
• Grosso AR, Leite AP, Carvalho S, Matos MR, Martins FB, Vítor AC, Desterro JM, Carmo-Fonseca M, de Almeida SF “Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma” eLife, 2015 Nov 17;4. pii: e09214. doi: 10.7554/eLife.09214
• Carvalho S, Vitor A, Sridhara SC, Martins FB, Raposo AC, Desterro JM, Ferreira J, de Almeida SF*. “SETD2 is required for DNA double-strand break repair and activation of the p53-mediated checkpoint” eLife, 2014 May 6. 10.7554/eLife.02482

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