Luís Belo

REQUIMTE, Caparica, Setúbal, Portugal

Are you Luís Belo?

Claim your profile

Publications (132)264.88 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinical studies showed that high doses of recombinant human erythropoietin (rHuEPO) used to correct anemia in chronic kidney disease (CKD) hyporesponsive patients may lead to deleterious effects. Our aim was to study the effects of rHuEPO in doses usually used to correct CKD-anemia (100, 200 IU/Kg body weight [BW]/week) and in higher doses used in the treatment of hyporesponsive patients (400, 600 IU/Kg BW/week), focusing on renal damage, hypoxia, inflammation and fibrosis. Male Wistar rats with chronic renal failure (CRF) induced by 5/6 nephrectomy were treated with rHuEPO or with vehicle, during 3 weeks. Hematological, biochemical and renal function analysis were performed. Kidney and liver mRNA levels were evaluated by qPCR and protein expression by western blot and immunohistochemistry. Kidney histopathological evaluations were also performed. CRF group developed anemia, hypertension and a high score of renal histopathologic lesions. Correction of anemia was achieved with all rHuEPO doses, with improvement in hypertension, renal function and renal lesions. In addition, the higher rHuEPO doses also improved inflammation. Blood pressure was reduced in all rHuEPO treated groups, compared to CRF group, but increased in a dose-dependent manner. Our study showed that rHuEPO treatment corrected anemia and improved urinary albumin excretion, particularly at lower doses. In addition, it is suggested that a short-term treatment with high doses, used to overcome an episode of hyporesponsiveness to rHuEPO therapy, can present benefits by reducing inflammation, without worsening of renal lesions; however, the pro-hypertensive effect should be considered, and carefully managed to avoid a negative cardiorenal impact. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · Clinical and Experimental Pharmacology and Physiology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy.
    Full-text · Article · Dec 2015 · International Journal of Molecular Sciences

  • No preview · Article · Sep 2015 · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
  • [Show abstract] [Hide abstract]
    ABSTRACT: Anemia is a common complication in patients with chronic kidney disease (CKD), mainly due to inadequate renal production of erythropoietin. In hemodialysis (HD) patients this condition may be aggravated by iron deficiency (absolute or functional). The correction of this anemia is usually achieved by treatment with erythropoiesis stimulating agents (ESAs) and iron (oral or intravenous). Studies questioning the safety of ESAs (especially at higher doses) changed the pattern of anemia treatment in CKD patients. According to the new guidelines, when transferrin saturation is lower than 30% and ferritin lower than 500. ng/mL, a trial with iron should be started, to avoid therapy with ESAs or at least to reduce the doses needed to treat the anemia. Recent reports showed increasing ferritin levels, towards values above 800. ng/mL, in CKD patients treated according to the guidelines. In this review we focus on the risks of the increased iron use to treat CKD anemia, namely, iron overload and toxicity, increased risk of infections, as well as mortality.
    No preview · Article · Aug 2015 · Blood Reviews
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine the effects of a school-based exercise intervention programme on cardiovascular risk factors, including body fat (BF), metabolic profile and physical activity (PA) in children with and without individualised dietary counselling approach (IDC and WIDC). Forty-six overweight children from 6-16 years old (25 girls, 54.3%; age = 10.3 ± 2.8) of six schools took part in an 8-month interdisciplinary, school-based intervention programme. All children were engaged in PA classes, but only one group was exposed to individualised counselling. Blood pressure (BP), lipids and lipoproteins, accelerometer-based PA, percentage of body fat (%BF) and trunk fat (%TF) measures were taken before and after intervention. General Linear Model (Repeated Measures ANOVA) adjusted for age, maturation and height change was used to analyse the longitudinal effect of individualised counselling between two evaluations in each group. Favourable changes were observed for %BF, %TF, systolic BP and total cholesterol in the IDC group. Subjects WIDC only increased light and moderate-vigorous PA. In IDC, significant effects for time * group interactions were found for systolic BP, total cholesterol and LDL-cholesterol, indicating that counselling might add favourable changes in these markers, beyond those explained by PA and growth. School-based interventions can contribute to counteracting obesity in youth, particularly when individualised dietary counselling is provided. Therefore, the link between schools and professional counselling should be strengthened to ensure consolidated changes towards healthy behaviours.
    Full-text · Article · Jul 2015 · Annals of Human Biology
  • Source

    Full-text · Article · Jun 2015 · Appetite
  • Source

    Full-text · Conference Paper · May 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: To evaluate interventions for improving fundamental motor skills (FMS) and physical activity (PA) levels in preschoolers. Mastery in FMS is associated with greater participation in PA in school aged children. Early childhood has been identified as the critical time for engaging in FMS development, however, there is limited research investigating this relationship in preschoolers aged 3-5 years. METHOD: We conducted a systematic search of electronic databases up until 31st October 2014. Randomised control trials (RCTs) using PA interventions with FMS as outcome measures in preschoolers were eligible for inclusion. Studies including children with disabilities or developmental delays were excluded. Between group mean differences, relative effect sizes (ES) and 95% confidence intervals were calculated for each outcome. RESULTS: Search terms yielded 1411 articles of which 8 RCTs and 2747 participants met the inclusion criteria. Studies were dichotomised into two groups (i) Teacher-Led (TL) Interventions (n=7) and (ii) Child-Centred (CC) Interventions (n=1). Mean age of children studied was 4.0±0.8yrs, with an equal gender distribution. Mean body mass index (BMI) was 16.52±0.23. On average interventions ran for 24±10wks, 3±1 times per week for 27±6mins. Five of the 7 TL studies reported significant improvements in FMS (ES Range 0.21-0.85;p≤0.01). The CC intervention also reported significant improvements in FMS, p≤0.001. Five TL interventions reported changes in PA levels, with one reporting significant improvements (ES 0.47;p≤0.01). Four studies reported body composition, with one reporting a significant decrease in BMI (p=0.02) and waist circumference (p=0.002). CONCLUSION: There is emerging evidence that PA interventions can improve FMS in preschoolers; however, there is a dearth of evidence on CC interventions, where an intervention is delivered directly to children by a trained professional. Targeting FMS development in this age group may promote higher PA levels throughout childhood, however more study is needed. Long term follow up is required to determine if improving FMS at preschool age increases participation in sports and PA. In addition, will it lead to lifestyle patterns throughout adolescence and adulthood, that will reduce the risk of metabolic and cardiovascular diseases. 1423 Board #216 May 28, 8:00 AM-9:30 AM Effects Of 6-month Soccer And Traditional Physical Activity Programs On Body Composition, Cardiometabolic, Inflammatory And Oxidative Markers In Obese Boys
    Full-text · Conference Paper · May 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Anemia is a common complication of chronic kidney disease (CKD) that develops early and its severity increases as renal function declines. It is mainly due to a reduced production of erythropoietin (EPO) by the kidneys; however, there are evidences that iron metabolism disturbances increase as CKD progresses. Our aim was to study the mechanisms underlying the development of anemia of CKD, as well as renal damage, in the remnant kidney rat model of CKD induced by 5/6 nephrectomy. This model of CKD presented a sustained degree of renal dysfunction, with mild and advanced glomerular and tubulointerstitial lesions. Anemia developed 3 weeks after nephrectomy and persisted throughout the protocol. The remnant kidney was still able to produce EPO and the liver showed an increased EPO gene expression. In spite of the increased EPO blood levels, anemia persisted and was linked to low serum iron and transferrin levels, while serum interleukin (IL)-6 and high sensitivity C-reactive protein (hs-CRP) levels showed the absence of systemic inflammation. The increased expression of duodenal ferroportin favours iron absorption; however, serum iron is reduced which might be due to iron leakage through advanced kidney lesions, as showed by tubular iron accumulation. Our data suggest that the persistence of anemia may result from disturbances in iron metabolism and by an altered activity/function of EPO as a result of kidney cell damage and a local inflammatory milieu, as showed by the increased gene expression of different inflammatory proteins in the remnant kidney. In addition, this anemia and the associated kidney hypoxia favour the development of fibrosis, angiogenesis and inflammation that may underlie a resistance to EPO stimuli and reduced iron availability. These findings might contribute to open new windows to identify putative therapeutic targets for this condition, as well as for recombinant human EPO (rHuEPO) resistance, which occurs in a considerable percentage of CKD patients.
    Full-text · Article · Apr 2015 · PLoS ONE
  • Source

    Full-text · Article · Mar 2015 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Toxic effects of ultraviolet (UV) radiation on skin include protein and lipid oxidation, and DNA damage. The latter is known to play a major role in photocarcinogenesis and photoaging. Many plant extracts and natural compounds are emerging as photoprotective agents. Castanea sativa leaf extract is able to scavenge several reactive species that have been associated to UV-induced oxidative stress. The aim of this work was to analyze the protective effect of C. sativa extract (ECS) at different concentrations (0.001, 0.01, 0.05 and 0.1μg/mL) against the UV mediated-DNA damage in a human keratinocyte cell line (HaCaT). For this purpose, the cytokinesis-block micronucleus assay was used. Elucidation of the protective mechanism was undertaken regarding UV absorption, influence on (1)O2 mediated effects or NRF2 activation. ECS presented a concentration-dependent protective effect against UV-mediated DNA damage in HaCaT cells. The maximum protection afforded (66.4%) was achieved with the concentration of 0.1μg/mL. This effect was found to be related to a direct antioxidant effect (involving (1)O2) rather than activation of the endogenous antioxidant response coordinated by NRF2. Electrochemical studies showed that the good antioxidant capacity of the ECS can be ascribed to the presence of a pool of different phenolic antioxidants. No genotoxic or phototoxic effects were observed after incubation of HaCaT cells with ECS (up to 0.1μg/mL). Taken together these results reinforce the putative application of this plant extract in the prevention/minimization of UV deleterious effects on skin. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Jan 2015 · Journal of Photochemistry and Photobiology B Biology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Bilirubin can prevent lipid oxidation in vitro, but the association in vivo with oxidized low-density lipoprotein (Ox-LDL) levels has been poorly explored. Our aim is to the association of Ox-LDL with total bilirubin (TB) levels and with variables related with metabolic syndrome and inflammation, in young obese individuals. Findings: 125 obese patients (13.4 years; 53.6% females) were studied. TB, lipid profile including Ox-LDL, markers of glucose metabolism, and levels of C-reactive protein (CRP) and adiponectin were determined. Anthropometric data was also collected. In all patients, Ox-LDL correlated positively with BMI, total cholesterol, LDLc, triglycerides (TG), CRP, glucose, insulin and HOMAIR; while inversely with TB and HDLc/Total cholesterol ratio (P < 0.05 for all). In multiple linear regression analysis, LDLc, TG, HDLc and TB levels were significantly associated with Ox-LDL (standardized Beta: 0.656, 0.293, −0.283, −0.164, respectively; P < 0.01 for all). After removing TG and HDLc from the analysis, HOMAIR was included in the regression model. In this new model, LDLc remained the best predictor of Ox-LDL levels (β = 0.665, P < 0.001), followed by TB (β = −0.202, P = 0.002) and HOMAIR (β = 0.163, P = 0.010). Conclusions: Lower bilirubin levels may contribute to increased LDL oxidation in obese children and adolescents, predisposing to increased cardiovascular risk.
    Full-text · Article · Jan 2015 · Diabetology and Metabolic Syndrome
  • [Show abstract] [Hide abstract]
    ABSTRACT: Circulating cell-free DNA (cfDNA) may result from cell damage and DNA fragments release, and, therefore, might be increased in inflammatory conditions. Preeclampsia (PE), an important cause of maternal and fetal mortality, is an inflammatory and oxidative condition. Our aim was to quantify cfDNA in Portuguese preeclamptic pregnancies, in order to search for a relationship with inflammation, endothelial dysfunction and severity of the disease. Maternal blood was collected from 31 normal pregnant women and from 33 PE pregnant women in the 3rd trimester. Circulating cfDNA was measured in serum samples using a rapid direct fluorescent assay (Goldshtein et al. Ann Clin Biochem 2009;46:488-94), which does not require prior processing of samples, there is no need for DNA extraction and amplification, is accurate, sensitive, and reproducible. TNF-alpha, a pro-inflammatory cytokine and endothelial markers, tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) antigen and soluble vascular cell adhesion molecule (sVCAM) levels, were evaluated by enzyme-immunoassay. Cf-DNA, TNF-α, sVCAM, tPA and PAI-1 concentrations were significantly higher in PE pregnant women when compared with normotensive pregnant women. In PE pregnancy cfDNA was significantly and positively correlated with TNF-alpha, VCAM, tPA and PAI-1 levels. CfDNA levels were also positively correlated with the PE severity, estimated by proteinuria. Our data suggest that the associated inflammation and endothelial dysfunction in PE pregnancy seems to lead to an increase in cfDNA, and its levels seem to be a potential marker of PE severity. Thus, cfDNA might be a potential candidate in the noninvasive diagnostic field. Moreover, further studies are warranted to evaluate cfDNA value as a premature marker to the development of PE. C. Catarino: None. S. Coimbra: None.L. Belo:None. S. Rocha: None. M. Bicho: None. I. Rebelo: None. A. Santos-Silva: None. Copyright © 2014.
    No preview · Article · Jan 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Erythroid hypoplasia (EH) is a rare complication associated with recombinant human erythropoietin (rHuEPO) therapies, due to development of anti-rHuEPO antibodies; however, the underlying mechanisms remain poorly clarified. Our aim was to manage a rat model of antibody-mediated EH induced by rHuEPO and study the impact on iron metabolism and erythropoiesis. Wistar rats treated during 9 weeks with a high rHuEPO dose (200 IU) developed EH, as shown by anemia, reduced erythroblasts, reticulocytopenia, and plasmatic anti-rHuEPO antibodies. Serum iron was increased and associated with mRNA overexpression of hepatic hepcidin and other iron regulatory mediators and downregulation of matriptase-2; overexpression of divalent metal transporter 1 and ferroportin was observed in duodenum and liver. Decreased EPO expression was observed in kidney and liver, while EPO receptor was overexpressed in liver. Endogenous EPO levels were normal, suggesting that anti-rHuEPO antibodies blunted EPO function. Our results suggest that anti-rHuEPO antibodies inhibit erythropoiesis causing anemia. This leads to a serum iron increase, which seems to stimulate hepcidin expression despite no evidence of inflammation, thus suggesting iron as the key modulator of hepcidin synthesis. These findings might contribute to improving new therapeutic strategies against rHuEPO resistance and/or development of antibody-mediated EH in patients under rHuEPO therapy.
    Full-text · Article · Dec 2014 · BioMed Research International
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated the potential cardiovascular risk protection of bilirubin in hemodialysis (HD) patients. An enlarged set of studies were evaluated in 191 HD patients, including hematological study, lipid profile, iron metabolism, nutritional, inflammatory markers, and dialysis adequacy. The TA duplication screening in the UDP-glucuronosyltransferase 1 A1 (UGT1A1) promoter region was also performed. The UGT1A1 genotype frequencies in HD patients were 49.2%, 42.4%, and 8.4% for 6/6, 6/7, and 7/7 genotypes, respectively. Although no difference was found in UGT1A1 genotype distribution between the three tertiles of bilirubin, significant differences were found with increasing bilirubin levels, namely, a decrease in platelet, leukocyte, and lymphocyte counts, transferrin, oxidized low-density lipoprotein (ox-LDL), ox-LDL/low-density lipoprotein cholesterol ratio, apolipoprotein (Apo) A, Apo B, and interleukin-6 serum levels and a significant increased concentration of hemoglobin, hematocrit, erythrocyte count, iron, transferrin saturation, Apo A/Apo B ratio, adiponectin, and paraoxonase 1 serum levels. After adjustment for age these results remained significant. Our data suggest that higher bilirubin levels are associated with beneficial effects in HD patients, by improving lipid profile and reducing the inflammatory grade, which might contribute to increase in iron availability. These results suggest a potential cardiovascular risk protection of bilirubin in HD patients.
    Full-text · Article · Sep 2014 · BioMed Research International
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Toll-like receptors (TLRs) play a key role in the response of innate and adaptive immune system to microbial and endogenous ligands. Inflammation is a common feature in end-stage renal disease (ESRD) patients; however, the mechanisms/factors triggering the inflammatory process are still poorly clarified. Our aim was to analyze the impact of the c.-1486T>C and c.896A>G polymorphisms in TLR9 and TLR4 genes, respectively, on the inflammatory response of ESRD patients. Clinical and laboratory evaluation was carried out on 184 ESRD patients. Polymerase chain reaction followed by restriction fragmens length polymorphisms (PCR-RFLP) was employed for genotyping of TLR-4 c.896A>G and TLR-9 c.-1486T>C polymorphisms. The prevalence of AA and AG of TLR4 c.896A>G polymorphism in ESRD patients was 97.8% and 2.2%, respectively. None of the individuals showed a homozygous TLR4 polymorphism. Concerning the TLR9 c.-1486T>C polymorphism, we found that ESRD patients showed a prevalence of TC and CC genotypes of 57.1% and 20.6%, respectively. We found that the heterozygous patients for the TLR4 c.896A>G polymorphism presented an increased level in lymphocyte count, a decrease in neutrophil/lymphocyte ratio and in serum levels of hepcidin. Regarding the TLR9 c.-1486T>C polymorphism, we found that it is associated with decreased white blood cell and neutrophil counts, ferritin and CRP serum levels, and with an increase in serum levels of creatinine. Our data suggest that the presence of the studied polymorphisms is associated with a decreased inflammatory response in ESRD patients under hemodialysis, and, thus its presence might have beneficial effects in ESRD patients. Moreover, our data provide new insights in the role of TLR polymorphisms in renal disease, which might have impact in the near future for the development of innovative therapies.
    Full-text · Article · Sep 2014 · European Journal of Inflammation
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Waldenström’s macroglobulinemia (WM) is a lymphoproliferative disease of B lymphocytes, characterized by a lymphoplasmocytic lymphoma in the bone mar-row and by IgM monoclonal hypergammaglobulinemia. It was first described in 1944 by Jan Gösta Waldenström, reporting two patients with oronasal bleeding, lymphadenopathy, anemia, thrombocytopenia, high erythrocyte sedimentation rate and serum viscosity, normal radiography and bone marrow infiltrated by lymphoid cells. The WM is a rare disease with a typically indolent clinical course, affecting mainly individuals aged between 63 and 68 years. Most patients have clinical signs and symptoms related to hyperviscosity resulting from IgM monoclonal gammopa-thy, and/or cytopenias resulting from bone marrow infiltration by lymphoma. The differential diagnosis with other lymphomas is essential for the assessment of prognosis and therapeutic approach. Treatment of patients with asymptomatic WM does not improve the quality of life of patients, or increase their survival, being recommended, therefore, their follow-up. For the treatment of symptomatic patients, alkylating agents, puri-ne analogs and anti-CD20 monoclonal antibodies are used. However, the disea-se is incurable and the response to therapy is not always favorable. Recent stu-dies have shown promising results with bortezomib, an inhibitor of proteasomes, and some patients respond to thalidomide. In patients with relapse or refrac-tory to therapy, autologous transplantation may be indicated. The aim of this paper is to describe in detail the current knowledge on the pa-thophysiology of WM, main clinical manifestations, diagnosis, prognosis and treatment.
    Full-text · Article · Sep 2014 · Revista da Associação Médica Brasileira
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Olive leaf (OL) supplements are marketed as promoting health and supporting the body in preventing free radical damage. This study examined the effect of different concentrations of OL supplement on the haematological and lipid profile and on the oxidative stability of red blood cells (RBCs). A cohort of healthy pigs was used as a model in a single-centre, randomized, prospective pilot comparison. Twenty four pigs were assigned to three experimental diets: a control group fed the conventional diet and two groups fed the conventional diet supplemented at 50 and at 100 g/kg with OL, during 8 weeks. Blood was collected for haematological, biochemical, and haemostatic studies. OL supplementation resulted in a significant decrease in plasmatic triacylglycerols (TAGs) concentration, aligned with a lower body mass and fat storage but no significant reductions were found for low-density lipoprotein cholesterol (LDLc) and oxLDL levels. The use of the highest dose resulted in significant RBC membrane destabilization.
    Full-text · Article · Jul 2014 · Journal of Functional Foods

  • No preview · Article · Jun 2014 · British journal of biomedical science
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Bilirubin has potential antioxidant and anti-inflammatory properties. The UGT1A1*28 polymorphism (TA repeats in the promoter region) is a major determinant of bilirubin levels and recent evidence suggests that raised adiposity may also be a contributing factor. We aimed to study the interaction between UGT1A1 polymorphism, hematological and anthropometric variables with total bilirubin levels in young individuals. Methods 350 obese (mean age of 11.6 years; 52% females) and 79 controls (mean age of 10.5 years; 59% females) were included. Total bilirubin and C-reactive protein (CRP) plasma levels, hemogram, anthropometric data and UGT1A1 polymorphism were determined. In a subgroup of 74 obese and 40 controls body composition was analyzed by dual-energy X-ray absorptiometry. Results The UGT1A1 genotype frequencies were 49.9%, 42.7% and 7.5% for 6/6, 6/7 and 7/7 genotypes, respectively. Patients with 7/7 genotype presented the highest total bilirubin levels, followed by 6/7 and 6/6 genotypes. Compared to controls, obese patients presented higher erythrocyte count, hematocrit, hemoglobin and CRP levels, but no differences in bilirubin or in UGT1A1 genotype distribution. Body fat percentage was inversely correlated with bilirubin in obese patients but not in controls. This inverse association was observed either in 6/7 or 6/6 genotype obese patients. UGT1A1 polymorphism and body fat percentage were the main factors affecting bilirubin levels within obese patients (linear regression analysis). Conclusion In obese children and adolescents, body fat composition and UGT1A1 polymorphism are independent determinants of total bilirubin levels. Obese individuals with 6/6 UGT1A1 genotype and higher body fat mass may benefit from a closer clinical follow-up.
    Full-text · Article · Jun 2014 · PLoS ONE

Publication Stats

1k Citations
264.88 Total Impact Points

Institutions

  • 2015
    • REQUIMTE
      Caparica, Setúbal, Portugal
  • 2000-2015
    • University of Porto
      • • Departamento de Ciências Biológicas
      • • Institute for Molecular and Cell Biology
      • • Faculty of Pharmacy
      • • Department of Biochemistry
      Oporto, Porto, Portugal
  • 2010
    • Universidade Católica Portuguesa
      Lisboa, Lisbon, Portugal
  • 2000-2009
    • Institute for Molecular and Cell Biology
      Oporto, Porto, Portugal