Research Lines

Cardiovascular and Metabolic Diseases

Cardiovascular diseases (CVD), affecting the heart and blood vessels, are a leading cause of morbidity and mortality worldwide and represent a major burden for health care systems. One of the major risk factors for CVD is diabetes mellitus (DM), which is associated with both micro and macrovascular complications. Obesity, hypertension and dyslipidemia are also common in patients with DM, placing them at increased risk for cardiac events. A successful approach to a complex clinical issue, which can lead to personalized medicine and pave the way towards the development of more precise diagnosis tools and more efficient and effective therapies, implies a holistic and integrative perspective of Cardiovascular diseases. This research line combines strong synergies of expertise and skills from fundamental scientists and clinicians. The main objective of this research line is to foster an interdisciplinary approach to leverage translational research, grounded on a comprehensive perspective from molecule to man. To boost the existing capacities and competencies, crossing canonical and static boundaries between disciplines, this line brings together basic researchers and clinicians, supporting a strategy “from bench to bedside and back again”.

In terms of basic research, we investigate the strategies whereby cardiac cells communicate and the mechanisms involved in the maintenance of a healthy proteome. More specifically, we aim to elucidate how the disturbance of protein degradation and intercellular communication systems can contribute to CVD, with a particular focus on autophagy and gap junction and extracellular vesicle communication. Additionally, we are interested on the cellular and molecular mechanisms underlying the metabolic dysregulation associated with obesity, prediabetes, diabetes and its major vascular complications, focusing on oxidative stress, glycation, inflammation, dysbiosis and autonomic gastrointestinal dysfunction. Furthermore, we test therapeutic interventions - non-pharmacological (namely nutraceutical) and pharmacological -, targeting the main tissues contributing and sensing insulin resistance (particularly the adipose tissue and the liver), the organs where complications take place (namely the vascular endothelium and the kidney), and the gastrointestinal tract.

In terms of clinical competencies, the group has two highly differentiated areas, i) heart failure (HF) and ii) transplantation and interventional cardiology. The team integrates competencies and resources on i) advanced HF & transplantation, ii) coronary care, iii) percutaneous structural cardiac intervention, iv) advanced electrophysiology, v) pulmonary hypertension, vi) congenital heart diseases, vii) advanced imaging capabilities, viii) syncope and ix) telemedicine & telemonitorization.

Groups

Teams

Neuropharmacology and Neuropsychiatry

Mental well-being is integral to population health and highly contributes to the functioning of individuals, families, communities and the social and economic prosperity of society. In fact, Psychiatric disorders have a huge impact not only in the individual but in society in general. Translational research in mental disorders - from bench to bedside – is crucial to give a step forward in the comprehension of such diseases. Thus, our main goal is to unravel the neurobiology behind Psychiatric disorders to ultimately contribute to improve patient´s lives, keeping in mind that an early intervention during development would improve patient´s outcome.

Our group is focus on neurodevelopmental disorders and their repercussions in the adulthood. We aim to explore some disorders such as ADHD, anxiety, depression and drugs abuse, with particular focus on psychostimulants. Additionally, the role of adverse life events and specific brain insults, such as traumatic brain injury, as triggers of Psychiatric disorders is also being investigated. Some specific questions have been raised by the team as follows:

1. What happens to an ADHD brain without treatment or if the treatment is ceased? Or What are the consequences of methylphenidate (non)prescription?

2. What are the consequences of amphetamine-type stimulants (ATS) abuse/misuse?

3. Is there a link between early-life events and psychiatric events in the adulthood?

4. Immune “challenges” during neurodevelopment affect brain wiring and neuropsychiatric health in a gender-specific manner. Is this gender specification of risk to neuropsychiatric disorders mediated by microglia plasticity?

At the cellular level, the team is mainly exploring neuroinflammatory and neurovascular alterations. Glial cells are considered the immune cells of the central nervous system playing a key role in physiological brain development, including in synaptogenesis. Study of association between brain health and immune changes is a main goal of our team. Moreover, glial cells play also an important role at the blood-brain barrier (BBB). This dynamic barrier highly selective, comprise by endothelial cells (ECs) that form brain capillaries, is responsible for the protection and maintenance of brain microenvironment proper for neural function. Notwithstanding, this unique brain immune quiescence can be altered in various pathological processes and it is now accepted that brain endothelial cells have an active role on brain function.

Pharmacologic and non-pharmacologic strategies, including physical exercise, will be pursued by the team in an attempt to improve or prevent neuropsychiatric alterations.

Groups

Vision Diseases

Vision diseases, including retinal degenerative diseases (diabetic retinopathy, glaucoma and age-related macular degeneration), retinal ischemia, retinoblastoma, ocular melanoma and corneal diseases affect hundreds of millions worldwide. The pathophysiology of these diseases is still not completely understood and biomarkers for diagnosis and disease progression are lacking. Moreover, the majority of them have no cure and the treatments available are scarce and not effective in many patients. Thus, the identification of new biomarkers and new advanced therapeutic strategies are needed. After cataract and refractive surgeries many patients suffer from dysphotopsia (glare, halos, starbursts). These symptoms can be due to mechanisms occurring at neural level, and neuroadaptation and neuroplasticity of the brain may represent an important factor determining favourable outcomes.

Also, patients with brain neurodegenerative disorders experience visual abnormalities, sometimes even before the disease diagnosis. Since the retina can be assessed by non-invasive techniques, it can be explored as a window to or a mirror of the brain.

Our Group has members with a strong expertise in both animal models of vision diseases and clinical research, with excellent international connections. We are also bridging the gaps between basic and clinical research, designing new projects together and identifying translational projects. We are the unique National Reference Center for treatment of intra-ocular tumors.

The main goals of this Research Strand are:

1) to clarify the molecular and cellular mechanisms underlying ocular diseases, giving a particular attention to neuroinflammation;

2) to identify new therapeutic targets;

3) to identify new biomarkers for diagnosis and disease progression;

4) to develop advanced therapeutic strategies (light-activated nanoparticles, microparticles, intraocular implants, stem cell transplantation, viral vectors, photodynamic therapy, supraselective chemotherapy, cold atmospheric plasma);

5) to develop new protocols and surgical techniques;

6) to discovery ways of facilitating neuroadaptation.

Groups

Teams

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).

Groups

Palliative, End of Life and Bereavement Care

Palliative, end of life and bereavement care is one of the most neglected and complex areas of health systems today, one that affects all humans and that can only be understood by crosscutting disciplines. Global need for this care approach is fast-growing in an ageing and changed social world with limited care resources. Worldwide projections published in 2019, in which our group collaborated, showed the number of people dying with serious health-related suffering is set to double from 26 million in 2016 to 48 million in 2060. This includes children, adolescents and adults living and dying from complex chronic conditions. The loss of each of these persons leaves around five people grieving. Palliative, end of life and bereavement care should be accessible to all. Research is needed to help achieve this.

Our group brings together researchers and clinicians from different fields, working closely with patients and carers to act as a hub for interdisciplinary research and innovation.

As an emerging research strand of ICBR, our main goals are to build fresh knowledge and discover new ways of organising care, interventions and product solutions, with a view to help people live better with illness, death and bereavement, according to what is most important to them and with the best possible quality of life.

Groups

Palliative, End of Life and Bereavement Care Group

Financiado por Fundos FEDER através do Programa Operacional Factores de Competitividade – COMPETE 2020 e por Fundos Nacionais através da FCT – Fundação para a Ciência e a Tecnologia no âmbito do projecto Estratégico com referência atribuida pelo COMPETE: POCI-01-0145-FEDER-007440