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Area - Genetics - Leader - Isabel Marques Carreira

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Human Genome Variation in Health and Disease

Group Leader: Isabel Marques Carreira

Core CVs: Jorge M Saraiva and Joana B Melo


Genomic analysis has provided research opportunities, new approaches to therapeutic development, health care and public health management. These advances allows the assessment of the predisposition to certain diseases which implies more informed clinical management and lifestyle changes.

Understanding genetic predisposition to disease and knowledge of lifestyle modifications that change the potential for a disease is necessary to make informed choices. This multidisciplinary line promotes and disseminates fundamental, translational and clinical scientific research having as main vectors the interaction environment-genome in developmental disorders, aging-related chronic diseases, and cancer.

We aim to understand the impact of genetic/epigenetic factors and environmental/microenvironment exposures on health and on the susceptibility and course of disease. An important focus is to study genotypes, transcripts, methylation markers, proteins and metabolites together with environmental risk factors and clinical information as powerful tools to understand the human variability and networks underlying diseases. This multidisciplinary approach includes study of human genome variability, identification of new biomarkers, essential for disease risk and outcome prediction, and to identify new therapeutic targets translating into clinical research.

Main achievements in the last 5 years:

1) Understand the role of genomic CNVs in various neurodevelopmental disorders that lead to cognitive impairment, improving patients’ diagnosis and therapeutic interventions. We proposed a classification that contributes to the genotype/phenotype correlation, with the delineation of laboratory criteria which help to classify the various CNVs detected, clustering our findings of 1000 patients with developmental delay into 5 classes. Genetic characterization of human iPSC lines, namely from a patient with laterality defects and associated congenital heart anomalies carrying a DAND5 missense alteration.

2) Analyze the impact of fetal chromosomal disorders on maternal blood metabolome, exploring new putative biomarkers and demonstrating the potential of plasma metabolomics. We participated in the assessment of the urinary metabolite signature of prematurity in newborns.

3) Identification of single nucleotide polymorphisms (SNPs), and epigenetic abnormalities that may affect the risk of disease development and may constitute novel genetic risk markers for neoplasia’s susceptibility, providing new therapeutic targets. We showed that chromosomal rearrangements, ex i(17q), and CNVs are related with Chronic Lymphoblastic leukemia.

4) Identification of genomic and epigenetic signatures with capability to predict recurrences and/or metastasis in the head and neck cancer; establish patients' prognosis and survival and also correlated to different clinical-pathological features, such as anatomic site, tumor stage and risk factors;

5) Identification of new prognostic biomarkers with capability to help in the early detection, diagnosis and ultimately in the development of new therapeutic strategies for head and neck cancer.

Selected Publications in the last 5 years:

1. Rasmussen MB, Nielsen JV, Lourenço CM, Melo JB, Halgren C, Geraldi CVL, Wilson Marques Jr, Rodrigues GM, Thomassen M, Bak M, Hansen C, Ferreira SI, Venâncio M, Henriksen KF, Lind-Thomsen A, Carreira IM, Jensen NA, Tommerup N. Neurodevelopment disorders associated with dosage imbalance of ZBTB20 correlate with the morbidity spectrum of ZBTB20 candidate target genes. J Med Genet; 51(9):605-13. 2014. IF:6.335. Q1

2. Carreira IM, Ferreira SI, Matoso E, Pires LM, Ferrão J, Jardim AC, Mascarenhas A, Pinto M, Lavoura N, Pais C, Paiva P, Simões L, Caramelo F, Ramos L, Venâncio M, Ramos F, Beleza A, Sá J, Saraiva J, Melo MJ. Copy Number Variants Prioritization after array-CGH analysis - Portuguese experience from 1000 patients. Molecular Cytogenetics 8:103-12 2015 IF: 1.506. Q2

3. Diaz SO, Pinto J, Barros AS, Morais E, Duarte D, Negrao F, Pita C, Almeida MD, Carreira IM, Spraul M, Gil AM. Newborn urinary metabolic signatures of prematurity and other disorders: a case control study. J. Proteome Res 15:311−325. Epub 2015. 2016 IF: 4.268. Q1

4. Onofre I, Mendonça N, Lopes S, Nobre R, Melo JB, Carreira IM, Januário C, Gonçalves AF, Almeida LP (2016) Fibroblasts of Machado Joseph Disease patients reveal autophagy impairment Scientific Reports 6:28220-10 pages 2016. doi: 10.1038/srep28220.IF: 4.259. Q1

5. Pars S, Cristo F, Inácio JM, Rosas G, Carreira IM, Melo JB, Mendes P, Martins DS, de Almeida LP, Maio J, Anjos R, Belo JA Generation and characterization of a human iPS cell line from a patient-related control to study disease mechanisms associated with DAND5 p.R152H alteration. Stem Cell Res. 29:202-206. (2018) IF: 3.963. Q1

6. Ceroni JRM, Dutra RL, Honjo RS, Llerena JC Jr, Acosta AX, Medeiros PFV, Galera MF, Zanardo ÉA, Piazzon FB, Dias AT, Novo-Filho GM, Montenegro MM, Madia FAR, Bertola DR, de Melo JB, Kulikowski LD, Kim CA A Multicentric Brazilian Investigative Study of Copy Number Variations in Patients with Congenital Anomalies and Intellectual Disability. Sci Rep. 8(1):13382. (2018) doi: 10.1038/s41598-018-31754-2. IF: 4.259. Q1

7. Ribeiro IP, Marques F, Caramelo F, Pereira J, Patricio M, Pazeres H, Ferrão J, Julião MJ, Castelo-Branco M, Melo JB, Baptista IP, Carreira IM. Genetic gains and losses in oral squamous cell carcinoma: impact on clinical management. Cellular Oncology 37(1):29-39. Epub 2013 Dec 19. 2014 IF:3.032 Q1

8. Ribeiro IP, Caramelo F, Marques F, Domingues A, Mesquita M, Barroso L, Prazeres H, Julião MJ, Poiares Baptista I, Ferreira A, Melo JB, Carreira IM. WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report. Cellular Oncology 39(6):573-582. 2016 IF:3.786. Q1

9. Ribeiro IP, Esteves L, Menoita J, Caramelo F, Marques F, Barroso L, Miguéis J, Melo JB, Carreira IM. Genomic predictive model for recurrence and metastasis development in head and neck squamous cell carcinoma patients. Scientific reports. (Sci Rep). 7(1): 13897, Oct 24, 2017. IF: 4.259. Q1

10. Ribeiro IP, Caramelo F, Esteves L, Oliveira C, Marques F, Barroso L, Melo JB, Carreira IM. Genomic and epigenetic signatures associated with survival rate in oral squamous cell carcinoma patients. J Cancer. 9(11): 1885-1895. 2018. Doi:10.7150/jca.23239.

IF: 3.249. Q2


Integrated Members

Eunice Matoso (PhD)

Francisco Caramelo (PhD)

Francisco Corte-Real (MD PhD)

Henriqueta Breda (MD PhD)

Ilda Ribeiro (PhD)

Isabel Marques Carreira (PhD)

Isabel Poiares Batista (DMD PhD)

Joana Barbosa de Melo (PhD)

João Miguel Marques dos Santos (DMD PhD)

Jorge M Saraiva (MD PhD)

Maria José Julião (MD)

Mário Laço (MD PhD)



Carolino Monteiro (PhD)

Fernando Regateiro (MD PhD)

Fernando Ribeiro (PhD) Aveiro

Luísa Mota Vieira (PhD) Açores

Henrique Girão (PhD)

Carmen Alpoim (PhD)


Joris Veermesch (PhD) Center for Human Genetic, Leuven, Belgium

Leslei Kulikowski. University of S Paulo. Brasil

Niels Tommerup (MD PhD) Dept of Cellular and Molecular Medicine. University of Copenhagen

Thomas Liehr (PhD) Institute of Human Genetics, Jena, Germany.

PhD Students:

André Lázaro, MD

Daniela Santos Silva, DMD

Domingos Roda, MD

Celeste Alcobia, MD

Elisabete Resende, MD

Filipe Mira, MD

Francisco Marque, MD

Inês Santos, MSc

José Carlos Cardoso, MD

Joana Ribeiro, MD

Leonor Barroso, MD

Tony Rolo, DMD

Sheila Martins, MD