17 minute read
Part II. Knowledge Telmo
Part II. Knowledge
Telmo Catarino
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We are proud to share the great scientific contributions of the GABBA students and alumni, since the last newsletter. Among the list of publications, there are several articles that were published in prestigious high impact journals (original publications as first or senior author) that we will highlight here.
Oncobiology
Ana Luísa Correia recently published the work of her post-doc at Mohamed Bentires-Alj’s lab. In this newsletter, the 11th edition alumna told us about this project from the beginning. “I wanted to understand how breast cancer spreads to other organs. What really puzzled me was that while some patients develop metastatic disease soon after the primary tumor is found, others can go years or even decades before being diagnosed with metastasis. Many years of research have shown that at the root of this phenomenon are cancer cells that break away from the primary tumor and disseminate to other organs, where they remain dormant until they find themselves in growthsupporting conditions. Why these cells become dormant and what causes them to wake up are one of the most fundamental unsolved problems in cancer research.” In this work, she and her colleagues developed a molecular tool to follow dormant cancer cells in mice, with which she found that the liver was the tissue where they accumulated at the highest number. “This location was not surprising since the liver is one of the main sites of breast cancer metastasis. And because the liver is an essential organ, which is very difficult to treat, liver metastasis is a leading cause of death among breast cancer patients.” She found these dormant cancer cells are kept at bay by natural killer cells, showing that mice with enough natural killer cells in the liver would control the disease by inducing cancer cell dormancy. “But we know that the number of these cells can change, and the environment in each organ plays a critical role in this control.” In fact, they showed natural killer cell proliferation can be restricted by hepatic stellate cells, effectively limiting their number in the tissue.
Furthermore, when they treated mice with IL-15, the pool of natural killer cells was expanded, metastatic burden was reduced, and liver metastasis were prevented, also extending mice survival, although not eliminating the dormant tumor cell reservoir. “This provides a proof of concept, showing that therapies aimed at normalizing the natural killer cell numbers might prevent metastatic disease.” Results from this study are already being integrated into a first clinical study at the University Hospital Basel.
Correia AL, Guimaraes JC, Auf der Maur P, ... Bentires-Alj M (2021). Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy. Nature, 594(7864), 566–571.
Voabil P, de Bruijn M, Roelofsen LM, ... Thommen DS (2021). An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer. Nature Medicine, 27(7), 1250–1261.
Silva A, Almeida ARM, Cachucho A, ... Barata JT (2021). Overexpression of wild-type IL-7Rα promotes T-cell acute lymphoblastic leukemia/lymphoma. Blood, 138(12), 1040–1052.
Perera Y, Melao A, Ramon AC, ... Perea SE, & Barata JT (2020). Clinical-Grade Peptide-Based Inhibition of CK2 Blocks Viability and Proliferation of T-ALL Cells and Counteracts IL-7 Stimulation and Stromal Support. Cancers, 12(6).
Salta S, Maia-Moço L, Estevão-Pereira H, ... Jerónimo C (2021). Performance of DNA methylation-based biomarkers in the cervical cancer screening program of northern Portugal: A feasibility study. International Journal of Cancer, 149(11), 1916–1925.
Miranda-Gonçalves V, Lobo J, GuimarãesTeixeira C, ... Jerónimo C (2021). The component of the m(6)A writer complex VIRMA is implicated in aggressive tumor phenotype, DNA damage response and cisplatin resistance in germ cell tumors. Journal of Experimental & Clinical Cancer Research: CR, 40(1), 268.
Lobo J, Constâncio V, Guimarães-Teixeira C, ... Jerónimo C (2021). Promoter methylation of DNA homologous recombination genes is predictive of the responsiveness to PARP inhibitor treatment in testicular germ cell tumors. Molecular Oncology, 15(4), 846–865.
Macedo-Silva C, Miranda-Gonçalves V, Lameirinhas A, ... Jerónimo C (2020). JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma. Cell Death & Disease, 11(12), 1068.
Pereira C, Park J-H, Campelos S, ... Oliveira, C. (2021). Comparison of East-Asia and West-Europe cohorts explains disparities in survival outcomes and highlights predictive biomarkers of early gastric cancer aggressiveness. International Journal of Cancer.
Almeida GM, Pereira C, Park J-H, ... Oliveira, C. (2021). CD44v6 High Membranous Expression Is a Predictive Marker of Therapy Response in Gastric Cancer Patients. Biomedicines, 9(9).
Barbosa-Matos R, Leal Silva R, Garrido L, ... Oliveira C (2021). The CDH1 c.1901C>T Variant: A Founder Variant in the Portuguese Population with Severe Impact in mRNA Splicing. Cancers, 13(17).
Rocha S, Basto AP, Ijsselsteijn ME, ... Oliveira C (2021). Immunophenotype of Gastric Tumors Unveils a Pleiotropic Role of Regulatory T Cells in Tumor Development. Cancers, 13(3).
De Marchi P, Berardinelli GN, Cavagna R de O, ... Reis, R. M. (2021). Microsatellite Instability Is Rare in the Admixed Brazilian Population of Non-Small Cell Lung Cancer: A Cohort of 526 Cases. Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology, 1–6.
Rosa MN, E Silva LRV, Longato GB, ... Reis RM (2021). Bioprospecting of Natural Compounds from Brazilian Cerrado Biome Plants in Human Cervical Cancer Cell Lines. International Journal of Molecular Sciences, 22(7).
Novaes LAC, Sussuchi da Silva L, De Marchi P, ... Reis RM (2021). Simultaneous analysis of ALK, RET, and ROS1 gene fusions by NanoString in Brazilian lung adenocarcinoma patients. Translational Lung Cancer Research, 10(1), 292–303.
Gomes I, Moreno DA, Dos Reis MB, ... Reis RM (2021). Low MGMT digital expression is associated with a better outcome of IDH1 wildtype glioblastomas treated with temozolomide. Journal of NeuroOncology, 151(2), 135–144. Paço A, Leitão-Castro J, & Freitas R (2021). Epigenetic Regulation of CDH1 Is Altered after HOXB7-Silencing in MDAMB-468 Triple-Negative Breast Cancer Cells. Genes, 12(10).
de Bessa Garcia SA, Araújo M, Pereira T, & Freitas R (2021). HOXB7 Overexpression Leads Triple-Negative Breast Cancer Cells to a Less Aggressive Phenotype. Biomedicines, 9(5).
Paço A, Aparecida de Bessa Garcia S, Leitão Castro J, Costa-Pinto AR, & Freitas R (2020). Roles of the HOX Proteins in Cancer Invasion and Metastasis. Cancers, 13(1).
Cruz A, Carvalho CM, Cunha A, ... Cubiella J (2021). Faecal Diagnostic Biomarkers for Colorectal Cancer. Cancers, 13(21).
Sousa F, Costa-Pereira AI, Cruz A, ... Mendes Pinto I (2021). Intratumoral VEGF nanotrapper reduces gliobastoma vascularization and tumor cell mass. Journal of Controlled Release: Official Journal of the Controlled Release Society, 339, 381–390.
Maia J, Otake AH, Poças J, ... Costa-Silva B (2020). Transcriptome Reprogramming of CD11b(+) Bone Marrow Cells by Pancreatic Cancer Extracellular Vesicles. Frontiers in Cell and Developmental Biology, 8, 592518.
Immunology
Henrique Veiga-Fernandes is from the 1st GABBA edition and he is a group leader at Champalimaud Centre for the Unknown in Lisbon. He and his team recently identified a neuro-mesenchymal unit that translates cues from long-range neuronal circuitry and controls group 2 innate lymphoid cells, adipose tissue physiology, metabolism and obesity.
Cardoso F, Klein Wolterink RGJ, Godinho-Silva C, ... Veiga-Fernandes H (2021). Neuromesenchymal units control ILC2 and obesity via a brain-adipose circuit. Nature, 597(7876), 410–414.
Ferreira C, Barros L, Baptista M, ... Veldhoen M (2020). Type 1 Treg cells promote the generation of CD8(+) tissue-resident memory T cells. Nature Immunology, 21(7), 766–776.
Vanderkerken M, Baptista AP, De Giovanni M, ... Lambrecht BN (2021). ILC3s control splenic cDC homeostasis via lymphotoxin signaling. The Journal of Experimental Medicine, 218(5). Soares-da-Silva F, Freyer L, Elsaid R, ... Cumano A (2021). Yolk sac, but not hematopoietic stem cell-derived progenitors, sustain erythropoiesis throughout murine embryonic life. The Journal of Experimental Medicine, 218(4).
Lagnado A, Leslie J, Ruchaud-Sparagano M-H, ... Passos JF (2021). Neutrophils induce paracrine telomere dysfunction and senescence in ROS-dependent manner. The EMBO Journal, 40(9), e106048.
Rosa FF, Pires CF, Zimmermannova O, & Pereira C-F (2020). Direct Reprogramming of Mouse Embryonic Fibroblasts to Conventional Type 1 Dendritic Cells by Enforced Expression of Transcription Factors. Bio-Protocol, 10(10), e3619.
Cell Biology
Pedro Carvalho is a 3rd edition alumni and a group leader at the Sir William Dunn School of Pathology at Oxford University. In a recently published paper, through structural, biochemical and molecular dynamics simulation approaches, he and his team showed the mechanism of lipid droplet formation by the yeast Speipin Sei1 and its partner Ldb16, requiring sequential triacylglycerol-concentrating steps via distinct elements in the ER membrane and lumen.
Klug YA, Deme JC, Corey RA, ... Lea SM, & Carvalho P (2021). Mechanism of lipid droplet formation by the yeast Sei1/Ldb16 Seipin complex. Nature Communications, 12(1), 5892.
Chang YW, Overeem AW, Roelse CM, Fan X, Freund C, & Chuva de Sousa Lopes SM (2021). Tissue of Origin, but Not XCI State, Influences Germ Cell Differentiation from Human Pluripotent Stem Cells. Cells, 10(9).
Overeem AW, Chang YW, SpruitJ, Roelse CM, & Chuva De Sousa Lopes SM (2021). Ligand-Receptor Interactions Elucidate Sex-Specific Pathways in the Trajectory From Primordial Germ Cells to Gonia During Human Development. Frontiers in Cell and Developmental Biology, 9, 661243.
Mishra S, Taelman J, Chang YW, ... Heindryckx B, & Chuva De Sousa Lopes SM (2021). Sex-Specific Isolation and Propagation of Human Premeiotic Fetal Germ Cells and Germ Cell-Like Cells. Cells, 10(5).
Bates LE, Alves MRP, & Silva JCR (2021). Auxindegron system identifies immediate mechanisms of OCT4. Stem Cell Reports, 16(7), 1818–1831. Tremble KC, Stirparo GG, Bates LE, ... Silva JCR (2021). Sox2 modulation increases naïve pluripotency plasticity. IScience, 24(3), 102153.
Sobral AF, Chan F-Y, Norman MJ, ... Carvalho AX (2021). Plastin and spectrin cooperate to stabilize the actomyosin cortex during cytokinesis. Current Biology: CB.
Ferreira JV, & Carvalho P (2021). Pex30-like proteins function as adaptors at distinct ER membrane contact sites. The Journal of Cell Biology, 220(10).
Capitão AMF, Lopes-Marques M, Páscoa I, ... Castro LFC (2021). An ancestral nuclear receptor couple, PPAR-RXR, is exploited by organotins. The Science of the Total Environment, 797, 149044.
Silva TP, Pereira CA, Oliveira AR, ... da Rocha ST (2021). Generation and characterization of induced pluripotent stem cells from a family carrying the BRCA1 mutation c.3612delA. Stem Cell Research, 52, 102242.
Tavares L, Grácio P, Ramos R, Traquete R, Relvas JB, & Pereira PS (2021). The Pebble/Rho1/Anillin pathway controls polyploidization and axonal wrapping activity in the glial cells of the Drosophila eye. Developmental Biology, 473, 90–96.
Health and Environment Sciences
Luis Filipe Castro is from the GABBA 3rd edition and he is currently a group leader at CIIMAR. He and his teams showed that toothed whales displayed impaired sperm glycolysis due to gene and exon erosion, and that in dolphin spermatozoa fatty acid β-oxidation, but not carbohydrates, is required for motility. These observations of unique energetic rewiring supports the radical physiological reorganization caused by the transition to a marine environment poor in carbohydrates.
Alves LQ, Ruivo R, Valente R, ... Castro LFC (2021). A drastic shift in the energetic landscape of toothed whale sperm cells. Current Biology: CB, 31(16), 3648-3655. e9.
Almeida-Santos A, Martins-Mendes D, GayàVidal M, Pérez-Pardal L, & Beja-Pereira A (2021). Characterization of the Oral Microbiome of Medicated Type-2 Diabetes Patients. Frontiers in Microbiology, 12, 610370.
Borges DO, Patarrão RS, Ribeiro RT, ... Macedo MP (2021). Loss of postprandial insulin clearance control by Insulin-degrading enzyme drives dysmetabolism traits. Metabolism: Clinical and Experimental, 118, 154735.
Cunha C, Leite Pereira C, Ferreira JR, ... Santos SG, & Gonçalves RM (2021). Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCs. International Journal of Molecular Sciences, 22(17). de Bruijn R, Wright-Lichter JX, Khoshaba E, Holloway F, & Lopes PC (2020). Baseline corticosterone is associated with parental care in virgin Japanese quail (Coturnix japonica). Hormones and Behavior, 124, 104781.
Bollen Pinto B, Ribas Ripoll V, Subías-Beltrán P, ... Consortium OBOTS (2021). Application of an Exploratory Knowledge-Discovery Pipeline Based on Machine Learning to Multi-Scale OMICS Data to Characterise Myocardial Injury in a Cohort of Patients with Septic Shock: An Observational Study. Journal of Clinical Medicine, 10(19).
Bancessi A, Catarino L, José Silva M, Ferreira A, Duarte E, & Nazareth T (2020). Quality Assessment of Three Types of Drinking Water Sources in Guinea-Bissau. International Journal of Environmental Research and Public Health, 17(19).
Pereira A T, Schneider KH, Henriques PC, ... Gonçalves IC (2021). Graphene Oxide Coating Improves the Mechanical and Biological Properties of Decellularized
Umbilical Cord Arteries. ACS Applied Materials & Interfaces, 13(28), 32662–32672.
Pereira AT, Henriques PC, Schneider KH, ... Gonçalves IC (2021). Graphene-based materials: the key for the successful application of pHEMA as a bloodcontacting device. Biomaterials Science, 9(9), 3362–3377.
Laundos TL, Vasques-Nóvoa F, Gomes RN, ... Nascimento DS (2021). Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment. Frontiers in Cell and Developmental Biology, 9, 624601.
Garcez M, Branco-Santos J, Gracio PC, & Homem CCF (2020). Mitochondrial Dynamics in the Drosophila Ovary Regulates Germ Stem Cell Number, Cell Fate, and Female Fertility. Frontiers in Cell and Developmental Biology, 8, 596819. Alves LQ, Ruivo R, Valente R, ... Castro LFC l Garcez M, Branco-Santos J, Gracio PC, & Homem CCF (2020). Mitochondrial Dynamics in the Drosophila Ovary Regulates Germ Stem Cell Number, Cell Fate, and Female Fertility. Frontiers in Cell and Developmental Biology, 8, 596819.
Genetics and Gene Expression
Pedro Beltrão from GABBA 6th and his team recently published a high-throughput functional characterization of protein phosphorylation sites, using 474 yeast strains with specific phosphosites mutated that were screened for fitness in 102 conditions. In the case of phosphosites conserved in humans, the severity of the phenotypes seen in yeast is indicative of their human functional relevance. This approach allows functional characterization of individual phosphosites at highthroughput scale. Pedro is currently a group leader at EMBL-EBI and is joining ETH Zurich in 2022.
Viéitez C, Busby BP, Ochoa D, ... Beltrao P (2021). High-throughput functional characterization of protein phosphorylation sites in yeast. Nature Biotechnology.
Memon D, Gill MB, Papachristou EK, ... Miller ML, & Beltrao P (2021). Copy number aberrations drive kinase rewiring, leading to genetic vulnerabilities in cancer. Cell Reports, 35(7), 109155.
Bradley D, Viéitez C, Rajeeve V, Selkrig J, Cutillas PR, & Beltrao P (2021). Sequence and Structure-Based Analysis of Specificity Determinants in Eukaryotic Protein Kinases. Cell Reports, 34(2), 108602.
Fan X, Moustakas I, Torrens-Juaneda V, ... Chuva de Sousa Lopes SM (2021). Transcriptional progression during meiotic prophase I reveals sex-specific features and X chromosome dynamics in human fetal female germline. PLoS Genetics, 17(9), e1009773.
Castro J, Beviano V, Paço A, ... Francisco M, & Freitas R (2021). Hoxd13/Bmp2-mediated mechanism involved in zebrafish finfold design. Scientific Reports, 11(1), 7165.
Effa K, Rosenbom S, Han J, Dessie T, & BejaPereira A (2021). Genetic Diversities and Historical Dynamics of Native Ethiopian Horse Populations (Equus caballus) Inferred from Mitochondrial DNA Polymorphisms. Genes, 12(2).
Huylmans AK, Macon A, Hontoria F, & Vicoso B (2021). Transitions to asexuality and evolution of gene expression in Artemia brine shrimp. Proceedings. Biological Sciences, 288(1959), 20211720.
Elkrewi M, Moldovan MA, Picard MAL, & Vicoso B (2021). Schistosome W-linked genes inform temporal dynamics of sex chromosome evolution and suggest candidate for sex determination. Molecular Biology and Evolution.
Hernandez F, Conner BR, Richardson ME, ... Pesaran T, & Karam R (2021). Classification of the canonical splice alteration MUTYH c.934-2A>G is likely benign based on RNA and clinical data. Cold Spring Harbor Molecular Case Studies.
Siva-Jothy JA, & Vale PF (2021). Dissecting genetic and sex-specific sources of host heterogeneity in pathogen shedding and spread. PLoS Pathogens, 17(1), e1009196.
Costa G, Bradbury JJ, Tarannum N, & Herbert SP (2020). RAB13 mRNA compartmentalisation spatially orients tissue morphogenesis. The EMBO Journal, 39(21), e106003.
Ferreira FJ, Carvalho L, Logarinho E, & Bessa J (2021). foxm1 Modulates Cell NonAutonomous Response in Zebrafish Skeletal Muscle Homeostasis. Cells, 10(5).
Páleníková P, Harbour ME, Ding S, ... RebeloGuiomar P (2021). Quantitative density gradient analysis by mass spectrometry (qDGMS) and complexome profiling analysis (ComPrAn) R package for the study of macromolecular complexes. Biochimica et Biophysica Acta. Bioenergetics, 1862(6), 148399.
Wilton J, Tellier M, Nojima T, Costa AM, Oliveira MJ, & Moreira A (2021). Simultaneous studies of gene expression and alternative polyadenylation in primary human immune cells. Methods in Enzymology, 655, 349–399.
Neurosciences
André Sousa from the 11th GABBA edition is a research associate at Yale School of Medicine. He and his colleagues observed an anterior to posterior prefrontal cortex-enriched gradient of retinoic acid. Through genetic deletions of its receptors or catabolizing enzyme in mice, they report that retinoic acid signaling is important for proper molecular patterning of prefrontal and motor areas, development of posterior prefrontal cortex-mediodorsal thalamus connectivity and intra-posterior prefrontal cortex dendritic spinogenesis. Shibata M, Pattabiraman K, Lorente-Galdos B, ... Sousa AMM & Sestan N (2021). Regulation of prefrontal patterning and connectivity by retinoic acid. Nature, 598(7881), 483–488. AJ (2021). Reward-related gustatory and psychometric predictors of weight loss following bariatric surgery: a multicenter cohort study. The American Journal of Clinical Nutrition, 113(3), 751–761.
Nelson A, Abdelmesih B, & Costa RM (2021). Corticospinal populations broadcast complex motor signals to coordinated spinal and striatal circuits. Nature Neuroscience, 24(12), 1721–1732.
Botta P, Fushiki A, Vicente AM, ... Costa RM (2020). An Amygdala Circuit Mediates Experience-Dependent Momentary Arrests during Exploration. Cell, 183(3), 605-619.e22. Cunha C, Smiley JF, Chuhma N, ... Teixeira CM (2021). Perinatal interference with the serotonergic system affects VTA function in the adult via glutamate co-transmission. Molecular Psychiatry, 26(9), 4795–4812.
Manoel D, Makhlouf M, Arayata CJ, ... Saraiva LR (2021). Deconstructing the mouse olfactory percept through an ethological atlas. Current Biology: CB, 31(13), 28092818.e3.
Dias JM, Alekseenko Z, Jeggari A, ... Ericson J (2020). A Shh/Gli-driven three-node timer motif controls temporal identity and fate of neural stem cells. Science Advances, 6(38).
Ribeiro G, Camacho M, Fernandes AB, Cotovio G, Torres S, & Oliveira-Maia Todorov G, Mayilvahanan K, Cain C, & Cunha C (2020). Context- and Subgroup-Specific Language Changes in Individuals Who Develop PTSD After Trauma. Frontiers in Psychology, 11, 989.
Fontinha BM, Zekoll T, Al-Rawi M, ... TessmarRaible K (2021). TMT-Opsins differentially
modulate medaka brain function in a context-dependent manner. PLoS Biology, 19(1), e3001012.
Valente S, Marques T, & Lima SQ (2021). No evidence for prolactin’s involvement in the post-ejaculatory refractory period. Communications Biology, 4(1), 10.
Melo PN, Souza da Silveira M, Mendes Pinto I, & Relvas JB (2021). Morphofunctional programming of microglia requires distinct roles of type II myosins. Glia, 69(11), 2717–2738.
Ferreira-Pinto MJ, Kanodia H, Falasconi A, Sigrist M, Esposito MS, & Arber S (2021). Functional diversity for body actions in the mesencephalic locomotor region. Cell, 184(17), 4564-4578.e18.
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