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Activity Funded

Center for Drug Discovery and Innovative Medicines

Centro de Investigação Farmacológica e Inovação Medicamentosa

Reference
UIDB/04308/2020
Project Start Date
2020-01-01
Project End Date
2024-12-31
Principal Investigator
Scientific Area
Medical and health sciences
Funding Program
Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Base

Abstract

10.2 Summary in English for general dissemination purposes The MedInUP major goal is to identify multidisciplinary disease-oriented research projects leading to cutting edge R&D programmes in drug discovery to bolster pharmaceutical innovation and personalized medicine. This is grounded on synergies created for long between core departments. Research in MedInUP research is organized in the following interpenetrating topics: - Integrative Cell Signalling and Functional Bio-imaging - Drug Screening in Cellular and Animal Models - Cell Therapy and Regenerative Pharmacology - Innovation in Neuropsychiatric and Cardiometabolic Therapies - Drug Targeting in Inflammation and Pain - Drug Discovery, Biomarkers, and Translational Medicine The combination of multidisciplinary competencies in Pharmacology ensures MedInUP's ability to become a research unit capable of making a decisive contribution to transpose original biomedical research developed in its core and in other national and international biomedical research units in innovative, individualized and more effective therapies, an endeavour that is perfectly aligned with the country's need to strengthen its capacity to produce and export health goods and services and to improve the efficiency and sustainability of the national health care system. 10.3 Summary in English for evaluation The major goal of the Center for Drug Discovery and Innovative Medicines - MedInUP - at the University of Porto is to identify multidisciplinary disease-oriented research projects leading to cutting edge R&D programmes in drug discovery to bolster pharmaceutical innovation and personalized medicine. Strategically placed at the intersection of established academic and industrial expertise, MedInUP will fulfil both scientific and entrepreneurship objectives. MedInUP will translate ground-breaking research into more effective therapies in alignment with the needs and expectations of biotech and pharmaceutical companies in major therapeutic areas aiming innovative drug discovery programs. The MedInUP team of basic scientists, is grounded on a multidisciplinary team with specific interests on the prediction that cell-to-cell communication may be a key to control organ (dys)function, namely in what concerns (1) mechanosensing, pain and inflammation, (2) neuronal signalling, and (3) cardiovascular and renal homeostasis. Our aim in future research is to identify purinome-based drug targets by manipulating mechanisms responsible for the release of ATP from excitable and non-excitable cells and the metabolic pathways leading to fine-tuning control of purinoceptors activation. In addition, recent data from our group indicate that inhibition of alpha2C-adrenoceptors may influence L-DOPA uptake and dopamine synthesis, thus providing a hint for a putative novel target to treat Parkinson’s disease and psychiatric disturbances. Despite therapeutic advances and major research efforts, there is a low rate of blood pressure (BP) control among treated hypertensive patients and a poor prognosis of heart failure. The ultimate goal of our team will be at identifying novel therapeutic targets for these diseases focusing on the role of neuro-humoral pathways (sympathetic and dopaminergic regulation, purinergic neurotransmission/neuromodulation, stimulation of the endocannabinoid system, as well as the axis formed by RAAS and cyclooxygenase-derived mediators), sodium and amino acid sensing networks, oxidative stress and intracellular signalling. The team maintains an attractive and highly stimulating environment, particularly in terms of critical mass, research programs and new facilities. The MedInUP team of translational scientists, includes a cohesive team that integrates scientists with medical background in internal medicine, rheumatology, gastroenterology, dermatology, neurology, psychiatry cardiology, clinical pharmacology and pharmaceutical medicine, working side by side with basic scientists, is to translate basic science discoveries into novel therapeutic strategies, discover and validate new biomarkers, and implement a platform for emerging technologies (genomics, proteomics, metabolomics and bioimaging) for clinical trial research. Research activity will be focused in three major interconnected areas that concern (1) inflammation and tissue regeneration (mainly regarding bone, brain, cardiac, gut and skin), (2) neuropsychiatric therapies and (3) cardiometabolic therapies. The focus on inflammation and tissue regeneration is to understand the complexity of the inflammation response as a whole and in providing the ideal environment for tissue regeneration, mainly regarding bone, brain, cardiac, gut and skin regenerative strategies. Special attention will be given to novel targets directed to bone cell differentiation and cellular crosstalk in the bone microenvironment (with special focus on bone metabolic diseases) and address skin and intestinal oxidative stress induced injury to cellular macromolecules such as DNA, proteins and lipids, aiming the identification of biomarkers of disease progression and therapeutic prognosis of novel therapies that control inflammation, limit disease progression and prevent neoplastic transformation. The interest on novel molecular targets for treatment of epilepsy and neurodegenerative diseases such Parkinson, Alzheimer and Huntington as well in eating disorders (anorexia, bulimia and binge) will help with the understanding of epileptogenesis and neuroprotection, whereas research of neuronal mechanisms regulating the nutritional status in neurodegenerative disorders is of crucial importance for the maintenance of patients’ healthy status and disease control. Identification of interactions between classic neurotransmitters (noradrenaline, dopamine, serotonin, and acetylcholine) responsible by causality of neurodegenerative disorders and entities regulating food intake and general metabolism status such as leptin, ghrelin, neuropeptide Y and endocannabinoids, will be evaluated as potential sources for novel therapeutic interventions. Exploratory/observational studies will be conducted in patients with hypertension, heart failure and diabetes to evaluate the pathophysiological relevance of new mechanisms and targets (microRNAs, cyclooxygenase and lipoxygenase-derived pro-resolving pathways, purinergic regulation of metabolism and endothelial function, new RAS effectors), as well as clinical trials to test the safety and efficacy of novel therapeutic strategies. Other major aims include the evaluation of whether drug combinations currently used in cardiovascular medicine improve or impair the putative protective pathways, the discovery and validation of new biomarkers, and implementation of a platform for emerging technologies (genomics, proteomics, metabolomics and bioimaging) for clinical trial research. A major strength is the close interaction with major local hospitals and a network of clinical research groups PtCRIN (Portuguese Clinical Research Infrastructure Network), the largest Portuguese pharmaceutical company BIAL-Portela& Cª S.A., and Blueclinical Ltd, a clinical pharmacology expert company.

Institutions

Main Institutions

  • Centro de Investigação Farmacológica e Inovação Medicamentosa (MedInUP/ICBAS/UP)
  • Universidade do Porto Instituto de Ciências Biomédicas Abel Salazar (UP ICBAS)

Funding 196.850,00 €

Fundação para a Ciência e a Tecnologia (FCT) - Portugal

196.850,00 €