Cell Death and Disease


Helena L.A. Vieira

Principal Investigator
PhD in Cell Biology, Université Paris VII
Chemical Eng IST, Universidade Técnica de Lisboa




Campus Sant'Ana
Pólo de Investigação, NMS, UNL
Rua Câmara Pestana, nº 6
Lab 3.8
1150-082 Lisboa, Portugal

Phone: (+351) 218 803 101 (Ext: 26009)
Lab ext: 26025
E-mail: helena.vieira(at)nms.unl.pt

Main interests

Foto1The main interest is to disclose the biochemical pathways and the molecular target(s) involved in the biological function of carbon monoxide (CO) / heme-oxygenase (HO); with a particular focus on Cytoprotection and Differentiation of neural cells following cerebral ischemia.

The group is also interested in understanding the biochemical processes behind the hormetic responses induced by polyphenols, particularly in mitochondria, giving emphasis to the promising cardioprotective potential of these compounds.

The Cell Death and Disease Lab focuses on the crosstalk between Apoptosis, Autophagy, Metabolic shifts and Cell differentiation (in particular neurogenesis). The objective is to integrate all these cellular processes, with a particular focus on mitochondria, which are essential organelles due to their key role in modulating cell metabolism, redox processes and cell death.

Research Areas

Foto3Cerebral ischemia is the main cause of brain damage and the 3rd cause of death in western societies. In adults it is mainly due to stroke, whereas in infants is caused by perinatal complications, which are a serious clinical problem. In particular, perinatal hypoxic-ischemic encephalopathy (HIE), which is caused by birth asphyxia or uterine and fetal blood flow interruption, corresponds to 23% of all neonatal deaths worldwide, being one of the top 20 leading causes of burden of disease in all age groups (World Health Organization).
Despite being a disease with an enormous impact, the approved clinical therapies are limited. Thus, there is an urgent need to investigate the cellular pathways involved in neural cell injury, cytoprotection and cellular renewal, with innovative conceptual and methodological approaches, that may eventually lead to novel therapies.


Gaseoustransmitters stand at the cutting edge of biomedical research. The concept that nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) hold the potential to effectively treat disease has been solidly established in the last decade, with high-level publications and patents increasing steeply. However, their molecular targets are still poorly studied.
Proposing carbon monoxide as a therapeutic molecule is counter-intuitive, since for many decades, it has been primarily viewed as a toxic gas. CO gas is produced endogenously during the degradation of heme by heme-oxygenase (HO), being an enzyme that is activated or expressed in response to stress. CO has been recognized as a ubiquitous signalling molecule necessary for cells to counteract oxidative stress and injury, being cytoprotective and maintaining cellular homeostasis.


main Cardiovascular Diseases are a group of disorders affecting the heart and blood vessels. Globally, about 30% of deaths are related to Cardiovascular Diseases, with data suggesting that unbalanced diet and/or ageing are cumulative risk factors. Therefore it is crucial to investigate and propose novel and cost-effective therapies to decrease the risk of cardiovascular diseases.
Several reports have suggested a link between polyphenols enriched diets and lower risk of cardiovascular disease. Berries, a good source of polyphenols, especially anthocyanins, have been associated with improvements in cardiovascular risk profiles in several studies. Anthocyanins have been described as able to decrease oxidative damage and inflammation in models of cardiovascular diseases.


Foto9 Experimental models and strategies:

• Primary culture of astrocytes and neurons – for assessing cell and non-cell autonomous effect of CO/HO pathways
• Primary culture of cardiomyocytes;
• Human embryonic carcinoma stem cell line;
• Cardiomyocytes cell line;
• Organotypic cultures of hippocampus and cortex;
• Isolated mitochondria from brain and heart;
• In vivo rodent cerebral ischemia (perinatal ischemia)
• In vivo preclinical rodent models of cardiovascular diseases;
• Access to transgenic mice (GFP-LC3, Atg5-/- KO)

Our final aim is to understand the cellular and biochemical pathways involved in CO/HO-induced cytoprotection and cellular renewal in neuronal cells and the biochemical processes involved in polyphenols-induced hormetic responses in cardiomyocytes. The following aspects are targeted: cellular metabolic shifts and cytoprotection (in particular the central role of mitochondria), autophagy and neurogenesis (balance between progenitor cell proliferation and neuronal differentiation). Still, we have an interest on translational biomedical research development for the identification of new biomarkers (mainly related to HO pathways) in human samples of perinatal cerebral ischemia.


Imagens 11 e 12

"Remote ischemic per-conditioning in acute stroke – clinical trial for improving outcome and disclosing novel circulating biomarkers"
Funded by iNOVA4Health Unit
PI: Helena L. A. Vieira and Miguel Viana Baptista
FCT-ANR/NEU-NMC/0022/2012 - “Translational and mechanistic approaches on carbon monoxide as a modulator of neuroinflammation and neuroprotection in glial cells”
Funded by “Fundação para a Ciência e a Tecnologia” and “Agence Naional pour la Recherche”
PI: Helena L.A. Vieira and Roberto Motterlini

ANR-FCT/BEX-BCM/0001/2013 - “Mechanisms of cardioprotection by berries driven polyphenols”
Funded by “Fundação para a Ciência e a Tecnologia” and “Agence Naional pour la Recherche”

PI: Cláudia Santos (iBET) and Catherine Brenner (Université de Paris-Sud)

Municipal Prize for Young Scientists, County of Oeiras 2011 – “Começar em Oeiras” funded by Câmara Municipal de Oeiras, Portugal

COST Action BM 1005 “Gasotransmitters: from basic science to therapeutic applications (ENOG: European Network on Gasotransmitters)” (2011-2014) – Helena L.A: Vieira member of Management Committee.

PTDC/SAU-NEU/089747/2008 - “Preconditioning triggered by Carbon monoxide: new strategies to prevent brain damage due to hypoxia-ischemia and reperfusion”
Funded by “Fundação para a Ciência e a Tecnologia”
PI: Helena L.A. Vieira

PTDC/SAU-NEU/64327/2006 - “Carbon monoxide as neuroprotector against hypoxia-ischemia and reperfusion”
Funded by “Fundação para a Ciência e a Tecnologia”
PI: Helena L.A. Vieira

PTDC/SAU-TOX/112264/2009 - “Chronic Intermittent Eucapnic Hypoxia: systemic effects and evaluation of anti-hypertensive drugs efficacy”
Funded by “Fundação para a Ciência e a Tecnologia”
PI: Emília C. Monteiro


Selected Publications

Imagem 5 e 7 pubs

Book chapters

  • Carlos C. Romão and Helena L. A. Vieira in "Organometallic Chemistry: Recent Advances, ICOMC Silver/Gold Jubilee Book", A. J. L. Pombeiro Editor, J. Wiley, 2013 (in press) ISBN: 9781118510148
  • Carlos C. Romão and Helena L. A. Vieira, Metal Carbonyl Pro-drugs: CO delivery and beyond. in Bioorganometallics, G. Jaouen and M. Salmain Eds, Wiley-VCH, 2nd edition, 2013 in press


Imagem2 e 6 collaborations

• Roberto Motterlini, University of Paris-Est, FRANCE - See More

• Paula M. Alves, PhD Animal Cell Technology Unit, IBET and ITQB Universidade Nova de Lisboa, PORTUGAL - See More

• Miguel Viana-Baptista, MD PhD, CEDOC

• Alessandro Vercelli, MD PhD, Universidà degli studi di Torino, ITALY
homepage NICO

• Catherine Brenner-Jan, PhD, Faculté de Pharmacie, Université de Paris-Sud, France

• Emília Monteiro, MD, PhD, Lisbon Medical School, Universidade Nova de Lisboa, PORTUGAL - See More

• Patricia Boya, PhD, Centro de Investigaciones Biológicas, CIB-CSIC, Madrid, SPAIN - See More

• Carlos Romão, PhD, ITQB, PORTUGAL - See More

• Carlos Duarte, PhD, Universidade de Coimbra, PORTUGAL - See More at FCTUC or at CNC

• Gonçalo Cassiano Santos, MD, Grupo Hospitalar Lisboa Central, Maternidade Alfredo da Costa and Hospital dos Lusiadas, PORTUGAL

Team photos



IMG_9584GEL Helena Vieira