Disease Pathways & Biomarkers

Drugs Targets and Biomarkers
DPB Research Labs

The DPB group is deeply committed to the elucidation of the underlying causes and mechanisms of health, aging and disease, as well as to the identification of biomarkers and discovery of new therapeutic targets/drugs. In this context:

Molecular Mechanisms of Disease lab explores how endogenous mechanisms of defense protect cells against damage, in particular in the Central Nervous System against ischemic stroke. Two strategies are followed: (1) The use of carbon monoxide to prevent neuroinflammation and neuronal and glial cell death, to improve cell metabolism and maintain homeostasis. (2) In the second strategy we study the underlying mechanisms of remote ischemic conditioning, which is the ischemic conditioning (or hormesis) of non-vital organs (such as arms) that provide protection in another organ, such as brain against ischemic stroke. Still, identification of stroke biomarkers for stroke differential diagnosis is also a subject of research.

Drug Target and Biomarkers Lab explores the: i) importance of cannabinoid signaling and impact of exogenous cannabinoids in reproduction/infertility; ii) new targets/drugs to improve ER+ breast cancer therapy; iii) identification of biomarkers of initial renal damage, progression and mortality prediction; iv) role of antioxidant enzymes in the biology of non-immune hemolytic anemia, modulation of erythropoiesis and as potential therapeutic targets; v) development of educational programs and interventions for the elderly and health professionals to improve therapy adherence and prevent/mitigate frailty, and tools to evaluate implementation of technological solutions. Our major contributions were: In pregnancy, phytocannabinoids impact estrogen signaling, which may explain cannabis consumption negative pregnancy outcomes or, even, infertility. In Breast cancer, androgen receptor antagonism is a potential therapeutic strategy to overcome Exemestane-acquired resistance or enhance exemestane efficacy. In end-stage renal disease, the circulating levels of cell-free DNA is positively associated to inflammation, anemia and oxidative stress, and has predictive value for all-cause mortality and cardiovascular mortality in these patients. In Hereditary Spherocytosis, some typically cytosolic antioxidant enzymes bind to the erythrocyte membrane, preventing membrane lipoperoxidation and maintaining its integrity.

Recent publications
Silva, RFO; Pinho, BR; Monteiro, NM; Santos, MM; Oliveira, JMA. 2022. Automated analysis of activity, sleep, and rhythmic behaviour in various animal species with the Rtivity software. Scientific Reports, 12, DOI: 10.1038/s41598-022-08195-z
Rui FOSilva; Brígida RPinho; Miguel MSantos; Jorge MAOliveira. 2022. Disruptions of circadian rhythms, sleep, and stress responses in zebrafish: New infrared-based activity monitoring assays for toxicity assessment. CHEMOSPHERE, 305, DOI: 10.1016/j.chemosphere.2022.135449
Liliana MAlmeida; Brígida RPinho; Michael RDuchen; Jorge MAOliveira. 2022. The PERKs of mitochondria protection during stress: insights for PERK modulation in neurodegenerative and metabolic diseases. BIOLOGICAL REVIEWS, DOI: 10.1111/brv.12860
Pinho, BR; Almeida, LM; Duchen, MR; Oliveira, JMA. 2021. Allosteric activation of Hsp70 reduces mutant huntingtin levels, the clustering of N-terminal fragments, and their nuclear accumulation. LIFE SCIENCES, 285, DOI: 10.1016/j.lfs.2021.120009
Melo, D; Ferreira, F; Coimbra, S; Rocha, S; Santos-Silva, A. 2020. Ascorbic Acid as an Important Erythrocyte Antioxidant Defense in Patients with Non-immune Hemolytic Anemias - a preliminary study. FREE RADICAL BIOLOGY AND MEDICINE, 159, DOI: 10.1016/j.freeradbiomed.2020.10.084