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Environment, Genetics and Oncobiology (CIMAGO)

Many genetic complex interactions associated with environmental influences contributes to several developmental and chronic diseases/noncommunicable diseases (NCDs) such as cancer, a major human health problem worldwide. Furthermore, understanding genetic predisposition and lifestyle choices as contributors to the risk of developing and progression of these diseases, could contribute to prevention strategies and to diagnostic/prognostic and therapeutic improvement.

It had been observed, among patients with certain developmental syndromes, an increase in cancer risk. Aberrant cell proliferation, differentiation, migration and apoptosis are both characteristics of cancer and abnormal embryonic development. Environmental factors may play a key role in the pathogenesis of NCD, promoting the development of chronic low-grade inflammation.

Carcinogenesis is a multistep process involving genetic and epigenetic changes that contribute to the alteration in several cellular and molecular mechanisms that control cell growth, regulate sensitivity to cell death, and maintain genetic stability. Besides that, microenvironment, immune evasion, inflammation and metabolic dysregulation appear to be important mechanisms in NCD initiation and progression. Thus, the knowledge and understanding of the role of environment and cellular and molecular mechanisms underlying the disease contribute to develop new diagnostic, prognostic, drug response markers and to tailored targeted therapies.

This clinical and interdisciplinary research strand promotes and disseminates fundamental, translational and clinical scientific research in the areas of Environment, Genetics and Oncobiology. Its research activity has as main vectors the interaction environment-individual with the ultimate goal of precision medicine. An important aspect of this approach is the ability to predict the likelihood of disease, the outcome of treatment and the effectiveness of prevention.

Our strand has substantial expertise not only in basic and translational research, but also in clinical investigation. We work in close contact with hospitals involved in genetic and cancer diagnosis, prognosis and treatment, such as CHUC, IPO Coimbra and with Centro Académico Clínico.

This research strand has 4 main research groups (1 in the Environmental area, 1 in Genetics area and 2 in Oncobiology area), each one with a head coordinator, from FMUC and/or CHUC. Each group supports research activities of graduate students, MSc, PhD, post-doctoral fellows and clinical fellows (MDs). In addition, we have established collaborations with other National and International Research groups in the referred areas.

The main goals of this Research Strand are:

A multidisciplinary approach that includes the study of human genome variability, identification of new biomarkers, essential for disease risk and outcome prediction and the identification of new therapeutic targets translating into clinical research.

Integration of complex information from multiple data sources generating epidemiological studies, clinical trials and a usable clinical output, to support prevention, diagnostic, prognostic, and treatment strategies.

Specific aims:

- Understand the impact of environmental exposures and genetic/epigenetic variability on the susceptibility and course of developmental and NCD/chronic disorders;

- Analyze genotypes, transcripts, methylation markers, metabolites, immunoinflamation and immunologic response together with environmental risk factors and clinical information as powerful tools to understand the human variability and networks of underlying disorders;

- Identify relevant diagnostic, prognostic and drug response biomarkers to contribute to a better healthcare;

- Identify new therapeutic targets useful in treatment response monitorization, in patients risk stratification and in the selection of the best therapy or drug combination;

Using various in vitro and in vivo biological systems, NCD will be approached in a transversal way from the cellular and molecular mechanisms to new biomarkers and therapeutic targets, allowing an effective personalized medicine to promote well-being (Figure).