Research Lab

Molecular Mechanisms of Disease

mol mech disease 2024
58096

Lab Members

Lab leader

Helena L. A. Vieira

Senior Researcher

Inês Mollet

Master Students

Cristina Freitas
Rodrigo Martins
Tatiana Fernandes
Research Interests

Our broader scientific question tackles the mechanisms underlying stroke events in brain cells, and we aim to protect the brain tissue by targeting several cellular processes: apoptosis, inflammation, autophagy, metabolic shifts, redox signaling and neuronal differentiation. The final objective is to integrate this knowledge and to develop new approaches for protecting brain tissue based on:
(i) the cytoprotective function of carbon monoxide /heme-oxygenase
(ii) the activation of endogenous mechanisms of defense by remote ischemic conditioning.


Translational and clinically applied research on Stroke field concerns the identification of new biomarkers for differential stroke diagnosis: ischemic from hemorrhagic.

 

Identification of novel enteric therapeutic targets against type 2 diabetes - research on molecular mechanisms of metabolic diseases, in particular type 2 diabetes. Focus on enteric neuroendocrine signalling, therapeutic target identification and dietary bioactive compounds with therapeutic potential. Use of omics, human observational studies, rodent; pre-clinical; models, in-vitro human and rodent cell culture and organoids.

 

Research Highlights
Novel biomarkers for stroke differential diagnosis: ischemic from hemorrhagic

Stroke therapy is highly dependent on time window after stroke onset. Herein we have identified new proteid based biomarkers that may help stroke diagnosis will accelerate therapeutic decision.

Carbon monoxide (CO) prevents astrocytic cell death by improving mitochondrial homeostasis

CO tightly controls mitophagy of dyscfunctional mitochondria and increases mitochondrial biogenesis, which in turn is cytoprotective improving astrocytic metabolism and function.

 

highlight2020

 

Identification of novel enteric therapeutic targets against type 2 diabetes
duobetes

 

Representative Projects

  • Metabolism Reprogramming in Neuroblastoma – Pessoa program 022.15035.CBM Total funding € 12 000 – PI: Helena L.A. Vieira and Catherine Brenner (CNRS, France)
  • Screening for new high potential therapeutic targets in duodenum against type 2 diabetes - EXPL/MED-PAT/0852/2021 Total funding € 50 000 – PI: Inês Mollet
  • Remote ischemic post-conditioning in acute phase of ischemic stroke: disclosing novel circulating biomarkers and clinical trial for improving outcome - PTDC/MEC-NEU/28750/2017, Total funding € 239 900 - PI: Helena L A Vieira  and Co-PI: Miguel Viana-Baptista
  • Translational and mechanistic approaches on carbon monoxide as a modulator of neuroinflammation and neuroprotection in glial cells - FCT-ANR/NEU-NMC/0022/2012, Total funding € 249 000 - Funded by “Fundação para a Ciência e a Tecnologia” and “Agence Nationale pour la Recherche” - PI: Helena L.A. Vieira and Roberto Motterlini
  • Mechanisms of cardioprotection by berries driven polyphenols - ANR-FCT/BEX-BCM/0001/2013, Total funding € 187 800 - Funded by “Fundação para a Ciência e a Tecnologia” and “Agence Nationale pour la Recherche” - PI: Cláudia Santos (iBET) and Catherine Brenner (Université de Paris-Sud), Helena L Vieira responsible for one task
  • Preconditioning triggered by Carbon monoxide: new strategies to prevent brain damage due to hypoxia-ischemia and reperfusion, PTDC/SAU-NEU/089747/2008, Total funding € 100 000 - PI: Helena L A Vieira
  • Carbon monoxide as neuroprotector against hypoxia-ischemia and reperfusion - PTDC/SAU-NEU/64327/2006, Total funding € 125 000 – PI: Helena L A Vieira
     

Selected Publications

Marto, JP; Carvalho, AS; Mollet, IG; Mendonça, M; Salavisa, M; Meira, B; Fernandes, M; Serrazina, F; Cabral, G; Ventura, R; Sobral-Pinho, A; Beck, HC; Vieira, HLA; Viana-Baptista, M; Matthiesen, R. 2023. Proteomics to Identify New Blood Biomarkers for Diagnosing Patients With Acute Stroke. Journal of the American Heart Association, 12, DOI: 10.1161/JAHA.123.030021
Carrola, A; Romao, CC; Vieira, HLA. 2023. Carboxyhemoglobin (COHb): Unavoidable Bystander or Protective Player?. ANTIOXIDANTS, 12, DOI: 10.3390/antiox12061198
Figueiredo-Pereira, C; Villarejo-Zori, B; Cipriano, PC; Tavares, D; Ramirez-Pardo, I; Boya, P; Vieira, HLA. 2023. Carbon Monoxide Stimulates Both Mitophagy And Mitochondrial Biogenesis to Mediate Protection Against Oxidative Stress in Astrocytes. MOLECULAR NEUROBIOLOGY, DOI: 10.1007/s12035-022-03108-7
Inês Guerra Mollet; Catarina Martins; Miguel Ângelo-Dias; Carvalho AS; Kerman Aloria; Rune Matthiesen; M Viana-Baptista; LUIS MIGUEL BORREGO; Helena LAVieira. 2022. Pilot study in human healthy volunteers on the mechanisms underlying remote ischemic conditioning (RIC) – Targeting circulating immune cells and immune-related proteins. JOURNAL OF NEUROIMMUNOLOGY, DOI: 10.1016/j.jneuroim.2022.577847
Soares, NL; Paiva, I; Bravo, J; Queiroga, CSF; Melo, BF; Conde, SV; Romao, CC; Summavielle, T; Vieira, HLA. 2022. Carbon Monoxide Modulation of Microglia-Neuron Communication: Anti-Neuroinflammatory and Neurotrophic Role. MOLECULAR NEUROBIOLOGY, DOI: 10.1007/s12035-021-02643-z
Dias-Pedroso, D; Ramalho, JS; Sardao, VA; Jones, JG; Romao, CC; Oliveira, PJ; Vieira, HLA. 2021. Carbon Monoxide-Neuroglobin Axis Targeting Metabolism Against Inflammation in BV-2 Microglial Cells. MOLECULAR NEUROBIOLOGY, DOI: 10.1007/s12035-021-02630-4
Almeida, Ana S.; Soares, Nuno L.; Sequeira, Catarina O.; Pereira, Sofia A.; Sonnewald, Ursula; Vieira, Helena L.A.. 2018. Improvement of neuronal differentiation by carbon monoxide: role of pentose phosphate pathway. Redox Biology, 17, DOI: 10.1016/j.redox.2018.05.004