Research Lab

Computational Multi-Omics

29685

Lab Members

Research Interests

Our mission is to understand the (epi)genome biology and its impact on pathological conditions using computational multi-omics approaches. Such methods rely on the statistical analysis and integration of big data (high-throughput sequencing, microarrays, proteomics, high-throughput screening) and clinical/phenotypic data.

The regulation of (epi)genome and transcriptome networks is a crucial component of a healthy cell, but it is relatively unknown the molecular mechanisms underlying its misregulation in diseases: from cancer to age-related disorders. We have been deciphering pathological conditions through multiomics approaches, identifying molecular events to be further used as biomarkers and therapeutic targets.

Research Highlights

Unveiling the complexity of cell biology and underlying disregulation of diseases by deciphering multi-omics data

Through muti-omics profiling of a prospective cohort of 136 colorectal tumor biopsies we unveiled that mutational and chromosomal instability concertedly shape genetic and microenvironmental tumor heterogeneity (Sobral et al 2022, Communications Biology). Moreover, we demonstrated that tumor heterogeneity can be a prognostic marker of tumor relapse, where clonal diversity driven by large copy number alterations favors metastatic potential and multiple events of metastatic seeding. Overall, our findings unveiled that clonal diversity can influence microenvironment heterogeneity, differing across colorectal tumor subtypes and influencing tumor evolution and metastasis progression.

Representative Projects

"The cell of origin of PDAC: novel opportunities for the early diagnosis and treatment of PDAC" - La Caixa, Total Funding 1M€. Unit Funding: 150.000 €. Ana Rita Grosso (PI) (2023-2026)
"Dissecting the molecular mechanisms of X-chromosome inactivation using human embryonic stem cells" - FCT-MTES, Total Funding 250.000€. Unit Funding 107.000€. Ana Rita Grosso (co-PI) (2022-2025)
“Decoding pseudogene transcriptional regulation during cell differentiation” – FCT-MCTES, Total and Unit Funding: € 50,000. Ana Rita Grosso (PI) (2015-2019)
“Targeting Intra-Tumor heterogeneity as a promising therapeutic strategy for cancer”, FCT-MTES, Total and Unit Funding € 239,478. Ana Rita Grosso, (PI) (2018-2022)

Selected Publications

Silvia Carvalho; Luna Zea-Redondo; Tsz Ching Chloe Tang; Philipp Stachel-Braum; Duncan Miller; Paulo Caldas; Alexander Kukalev; Sebastian Diecke; Stefanie Grosswendt; Ana Rita Grosso; Ana Pombo. 2024. SRRM2 splicing factor modulates cell fate in early development. Biology Open, DOI: 10.1242/bio.060415

Paulo Caldas; Mariana Luz; Simone Baseggio; Rita Andrade; Daniel Sobral; Ana Rita Grosso. 2024. Transcription readthrough is prevalent in healthy human tissues and associated with inherent genomic features. Communications Biology, DOI: 10.1038/s42003-024-05779-5

Bruno ACardoso; Mafalda Duque; Ana Gírio; Rita Fragoso; Mariana LOliveira; James RAllen; Leila RMartins; Nádia CCorreia; André Bortolini Silveira; Alexandra Veloso; Shunsuke Kimura; Lisa Demoen; Filip Matthijssens; Sima Jeha; Cheng Cheng; Ching-Hon Pui; Ana RGrosso; João LNeto; Sérgio FDe Almeida; Pieter Van Vlieberghe; Charles GMullighan; JAndres Yunes; David MLangenau; Françoise Pflumio; João TBarata. 2023. CASZ1 upregulates PI3K-AKT-mTOR signaling and promotes T-cell acute lymphoblastic leukemia. Haematologica, DOI: 10.3324/haematol.2023.282854

Sabino, JC; de Almeida, MR; Abreu, PL; Ferreira, AM; Caldas, P; Domingues, MM; Santos, NC; Azzalin, CM; Grosso, AR; de Almeida, SF. 2022. Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops. eLife, 11, DOI: 10.7554/eLife.69476

Sobral, D; Francisco, R; Duro, L; Videira, PA; Grosso, AR. 2022. Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function. BIOMEDICINES, 10, DOI: 10.3390/biomedicines10081805

Sobral, Daniel; Martins, Marta; Kaplan, Shannon; Golkaram, Mahdi; Salmans, Michael; Khan, Nafeesa; Vijayaraghavan, Raakhee; et al. 2022. Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development. Communications Biology, 5, DOI: 10.1038/s42003-022-03884-x

Yu Ting Ong, Jorge Andrade and Max Armbruster, Chenyue Shi, Marco Castro, Ana S. H. Costa, Toshiya Sugino, Guy Eelen, Barbara Zimmermann, Kerstin Wilhelm, Joseph Lim, Shuichi Watanabe, Stefan Guenther, Andre Schneider, Francesca Zanconato, Manuel Kaulich, Duojia Pan and Thomas Braun, Holger Gerhardt, Alejo Efeyan, Peter Carmeliet, Stefano Piccolo, Ana Rita Grosso, Michael Potente. 2022. A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth. Nature Metabolism, 4, DOI: 10.1038/s42255-022-00584-y

Vanda Póvoa; Cátia Rebelo de Almeida; Mariana Maia-Gil; Daniel Sobral; Micaela Domingues; Mayra Martinez-Lopez; Miguel de Almeida Fuzeta; Carlos Silva; Ana Rita Grosso; Rita Fior. 2021. Innate immune evasion revealed in a colorectal zebrafish xenograft model. Nature Communications, DOI: 10.1038/s41467-021-21421-y

Andrade J, Shi C, Costa ASH, Choi J, Kim J, Doddaballapur A, Sugino T, Ong YT, Castro M, Zimmermann B, Kaulich M, Guenther S, Wilhelm K, Kubota Y, Braun T, Koh GY, Grosso AR, Frezza C, Potente M.. 2021. Control of endothelial quiescence by FOXO-regulated metabolites.. NATURE CELL BIOLOGY, DOI: 10.1038/s41556-021-00637-6

Prudêncio P, Rebelo K, Grosso AR, Martinho RG, Carmo-Fonseca M.. 2019. Analysis of Mammalian Native Elongating Transcript sequencing (mNET-seq) high-throughput data. METHODS, DOI: 10.1016/j.ymeth.2019.09.003