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Aline Ali Hamade

Associate professor
Life & Earth Sciences department - Section II - Fanar
Speciality: Biology
Specific Speciality: Biologie du dévelopement et cellules souches

Positions
2006 - present :

Lebanese University

2010 - 2014 :

Lebanese International University
Msaytbe

2010 - 2012 :

Kaslik University

2006 - 2014 :

Universite Saint Joseph
Mansourieh

Teaching 10 Taught Courses
(2014-2015) BioA 438 - Stem cells and differentiation

M1 Applied Animal Science

(2014-2015) BioA 439 - Stem cells and differentiation Lab

M1 Applied Animal Science

(2014-2015) CSMR 509 - Advances in developmental biology and stem cells

M2 Stem Cells, organogenesis and Regenerative Medicine

(2014-2015) RPDV 512 - Embryonic, fetal and perinatal differentiation

M2 Stem Cells, organogenesis and Regenerative Medicine

(2014-2015) BioA 438 - Stem cells and differentiation

M1 Cellular and Molecular Biology - Section 2

(2014-2015) BioA 439 - Stem cells and differentiation Lab

M1 Cellular and Molecular Biology - Section 2

(2014-2015) CSMR 580 - Training

M2 Stem Cells, organogenesis and Regenerative Medicine

(2014-2015) Biol 240 - Cell Biology Lab (Histology, Embryology, Reproduction, and genetics)

BS Earth and life sciences

(2014-2015) Biol 322 - Developmental Biology

BS Earth and life sciences

(2014-2015) Biol 342 - Developmental Biology Lab

BS Earth and life sciences

Education
SVT

Antonine University Mar Takla

Publications 9 publications
Myrna Medlej-Hashim1,2, Rania Jounblat2,†, Aline Hamade1,2,†, Jose Noel Ibrahim1,2, Francine Rizk1,2, Hypovitaminosis D in a Young Lebanese Population: Effect Annals of Human Genetics 2015

Bioactive vitamin D is a steroid hormone transported in blood via the vitamin D binding protein (DBP). Our study aimed to investigate the vitamin D status in a young Lebanese population and study the association of hypovitaminosis with levels of DBP. Polymorphisms in the GC gene that encodes DBP were also screened. Blood samples were collected from 179 university students. Vitamin D status and DBP levels were assayed by enzymelinked immunosorbent assay (ELISA). DNA was extracted from 128 participants, and genotyping of the two GC gene SNPs, rs7041, and rs4588, was carried out by restriction fragment length polymorphism. Forty-seven percent of participants had hypovitaminosis D (<20 ng/ml). A significant positive correlation was observed between vitamin D status and DBP. Genotyping data showed that participants carrying the rs7041 GG and rs4588 AA genotypes had higher concentrations of DBP than those carrying other genotypes. Four allelic versions of the GC gene were observed, one of which, GC∗3, was encountered for the first time in this study, and was found to be associated with both normal vitamin D and high DBP levels. Modifying genes such as GC could therefore affect DBP levels, and contribute, along with environmental factors, to the hypovitaminosis D observed in sunny countries.

Nassim H Abi Chahine1*, Johny R Rached2, Alaa F Abdelkarim3, Aline A Hamade4 and Victoria V Zoghbi5 Treatment of Long Standing Multiple Sclerosis with Regentime Stem Cell Stem Cell Research and Therapy 2015

This article is a case report in which we exposed the results of a multiple sclerosis (MS) patient, treated with stem cells. The 51 year old female patient was presenting with 23 year history of primary progressive type of MS. Her disease was physically debilitating causing numerous permanent complications during its long history, where different medications were used with no improvement; MS was progressing uncontrollably. Autologous bone marrow derived stem cells were outsourcing the procedure of treatment (Regentime® technique). This type of therapy was never previously used on such longstanding MS case and with such advanced impairment. Twelve main symptoms were studied and monitored during the post therapy care period. The follow up was done for 18 months before the publication of the results. We noticed a clear improvement at most levels, including a decrease in the headache, fatigue, hypertonia and dizziness. No regression was registered during the post-transplantation follow up period. We concluded that MS has positively responded to Regentime® procedure stem cell therapy even in its advance longstanding stage. This positive response may be due to the pathophysiological stepping nature of MS, where better improvements are seen in newer calling-for-repair lesions as shown in a previous study.

Aline Hamadé1,*, Sandra Bhanini1,2, Theresa Saade1,2, YoumnaFakih3, Chadi Fakih3, Rita Azzi1, Mira Hazouri2, Francine Rizk1 Vitamin D Levels in Serum, Vitamin D Receptor Polymorphisms and Semen Quality Correlations in Lebanon: A Pilot Cross-Sectional Study 2014

Background: The role of the steroid hormone Vitamin D (VD) and its nuclear receptor (VDR) in skeletal metabolism is well known. Furthermore, research suggests that VD plays a role in female and male reproduction. However, semen quality status is not clear in infertile men with different VD serum concentrations. The aim of this study is to measure serum VD levels in infertile Lebanese men, to investigate semen quality parameters and their correlation to serum VD levels and polymorphic variations in the VDR. Materials and methods: From March to April 2013, 40 men presenting to an IVF center located in Mount-Lebanon to undergo IUI or ICSI procedure were recruited to our study. VD in serum was evaluated using ELISA method. The polymorphic regions were amplified using PCR followed by digestion with restriction enzymes FokI (rs10735810), ApaI G/T(rs11168271), TaqI T/C(rs731236). Results: No correlation was found between the ApaI and FokI polymorphisms and both VD levels in serum (P= 0.367, P=0.75 respectively) and sperm count (P= 0.919).Positive correlation was found between ApaIpolymorphisms and the number of non progressive and immotile spermatozoa (P=0.012, P=0.033 respectively). Also, positive correlation was found between TaqIpolymorphisms and VD serum levels (P= 0.038). Conclusions: More studies on VD could be relevant of a potential VD supplementation that might improve semen quality of involuntary infertile men and would be beneficial both for the infertile couples and the society in general. VD supplementation can opens for a safe treatment of some cases of "idiopathic" impaired semen quality.

Rizk Francine1, Salameh Pascale2, Hamadé Aline3,* Congenital Anomalies: Prevalence and Risk Factors 2014

Objective: The aim of this study is to assess the incidence, types and correlates of congenital anomalies (CA) among stillborn and liveborn infants in two Lebanese hospitals in Mount-Lebanon. Methods: In this cross-sectional study, all the newborns who were born during 9 months period from January to December 2009 (n=1000) at two hospitals setting in Mount-Lebanon hospital, Lebanon were studied. The newborns were assessed for CA. Neonatal data were extracted from medical records of the nursery. The classification of malformations was based upon the anatomical system affected according to the WHO classification of CA. Results: Of the all 1000 single births, 24 (2.4%) were diagnosed as being congenitally malformed. Cardiovascular system defects and limbs anomalies (4/1000) were mostly detected, followed by genitourinary system (2/1000), nervous system (2/1000), respiratory system (2/1000) malformations and chromosomal anomalies (1/1000). A marked association of parental consanguinity and alcohol consumption of the mother during the pregnancy with increased CA rates was found (p= 0.015 and p=0.027 respectively). Conclusions: The frequency of malformations in the study was approximately similar to previous investigations. The increased incidence of CA in cases of parental consanguinity prompts the necessity of establishing educational programs to avoid these complications in the offspring.

Rabih El-Merahbi1., Yen-Nien Liu2., Assaad Eid1, Georges Daoud1, Leina Hosry3, Alissar Monzer1, Tarek H. Mouhieddine1, Aline Hamade4*, Fadia Najjar5*, Wassim Abou-Kheir1* Berberis libanotica Ehrenb Extract Shows Anti-Neoplastic Effects on Prostate Cancer Stem/Progenitor Cells 2014

Cancer stem cells (CSCs), including those of advanced prostate cancer, are a suggested reason for tumor resistance toward conventional tumor therapy. Therefore, new therapeutic agents are urgently needed for targeting CSCs. Despite the minimal understanding of their modes of action, natural products and herbal therapies have been commonly used in the prevention and treatment of many cancers. Berberis libanotica Ehrenb (BLE) is a plant rich in alkaloids which may possess anti-cancer activity and a high potential for eliminating CSCs. We tested the effect of BLE on prostate cancer cells and our data indicated that this extract induced significant reduction in cell viability and inhibited the proliferation of human prostate cancer cell lines (DU145, PC3 and 22Rv1) in a dose- and time-dependent manner. BLE extract induced a perturbation of the cell cycle, leading to a G0-G1 arrest. Furthermore, we noted 50% cell death, characterized by the production of high levels of reactive oxidative species (ROS). Inhibition of cellular migration and invasion was also achieved upon treatment with BLE extract, suggesting a role in inhibiting metastasis. Interestingly, BLE extract had a major effect on CSCs. Cells were grown in a 3D sphere-formation assay to enrich for a population of cancer stem/progenitor cells. Our results showed a significant reduction in sphere formation ability. Three rounds of treatment with BLE extract were sufficient to eradicate the self-renewal ability of highly resistant CSCs. In conclusion, our results suggest a high therapeutic potential of BLE extract in targeting prostate cancer and its CSCs.

Aline Hamade1,*, Francine Rizk1, Carine Genet2, Xavier Cousin3,4 Comparative expression Pattern of Two Vestigial-Like 2 Genes in Zebrafish 2013

The vestigial Vg gene, initially characterized in Drosophila, encodes a transcription co-factor which is crucial for wings development. Vg binds via its Sd interaction domain (SID) to the Scalloped (Sd) transcription factor and its vertebrate homolog Tef1. Previous studies identified several vertebrate genes sharing high homology with Drosophila Vg SID such as Vgl (for Vg-like), TONDU (also known as Vgl1) or Vito-1 (also known as Vgl2). In order to investigate the role of vestigial-like 2 (vgll2) in zebrafish muscle development, we managed to clone and characterize two zebrafishVgll2 homolog genes, Vgll2a and Vgll2b. Alignment data showed high sequence homology of Vgll2a to vertebrates Vgll2 sequences. In situ hybridization showed that the two investigated Vgll2 genes had a similar expression pattern: they were first detected in adaxial cells (11 hpf), than expanded laterally in somites and at the end of segmentation, both genes were expressed in additional structures including head muscles and fin buds. In addition, different expression patterns of the two genes were observed. Vgll2a was expressed in bronchial arches precursor streams, derived gill muscles and hypothalamic precursors. Vgll2b was expressed in notochord at 14 hpf and regressed following notochord maturation at 18hpf. Furthermore, the genetic regulation of vgll2 genes was analysed using smu mutants and data revealed that both genes are regulated via the Hedgehog signaling pathway.

Aline Hamadé (PhD)a, Pascale Salameh (MPH, PhD)b, Myrna Medlej-Hashim (PhD)a, Elie Hajj-Moussa (PhD)a, Nina Saadallah-Zeidan (PhD)c and Francine Rizk (PhD Autism in Children and Correlates in Lebanon: A Pilot Case-Control Study 2013

Background: Autism spectrum disorder (ASD) is a neurological disorder typically appearing before the age of three. The exact cause of autism remains uncertain, and several factors may be involved in its onset: genetic factors and possible environmental factors. The aim of this study was to assess the correlates of autism in the Lebanese population. Methods: We investigated the association of autism with several factors in 86 autism cases from specialized schools for children with developmental disabilities and 172 control children from regular public schools in the same regions. Several risk factors for autism were investigated after comparison with a cohort control on parental age, sex, maternal unhappy feeling during pregnancy, consanguineous marriage, and province of residence. The Chi-square test was used to compare nominal variables, and Fisher exact test was used in case expected values within cells were inferior to five. For quantitative variables, we used t-test to compare means between two groups, after checking their distribution normality. For multivariate analysis, we used a forward stepwise likelihood ratio logistic regression. Results: We observed male predominance (79.1%) among autistic infants. There was a significant association between autism and older parents age (OR=1.27), male sex (OR=3.38), unhappy maternal feeling during pregnancy (OR=5.77), living close to industry (OR=6.58), previous childhood infection (OR=8.85), but none concerning maternal age, paternal age and consanguinity. Conclusions: In this pilot epidemiological study of autism in Lebanon, we found several prenatal and perinatal risk factors for autism that could be modified.

Marina El Haddad1,*, Elise Jean1,*, Ahmed Turki1, Ge´ rald Hugon1, Barbara Vernus2, Anne Bonnieu2, Emilie Passerieux1, Aline Hamade3, Jacques Mercier1,4, Dalila Laoudj-Chenivesse1 and Gilles Carnac Glutathione peroxidase 3, a new retinoid target gene, is crucial for human skeletal muscle precursor cell survival 2012

Protection of satellite cells from cytotoxic damages is crucial to ensure efficient adult skeletal muscle regeneration and to improve therapeutic efficacy of cell transplantation in degenerative skeletal muscle diseases. It is therefore important to identify and characterize molecules and their target genes that control the viability of muscle stem cells. Recently, we demonstrated that high aldehyde dehydrogenase activity is associated with increased viability of human myoblasts. In addition to its detoxifying activity, aldehyde dehydrogenase can also catalyze the irreversible oxidation of vitamin A to retinoic acid; therefore, we examined whether retinoic acid is important for myoblast viability. We showed that when exposed to oxidative stress induced by hydrogen peroxide, adherent human myoblasts entered apoptosis and lost their capacity for adhesion. Pre-treatment with retinoic acid reduced the cytotoxic damage ex vivo and enhanced myoblast survival in transplantation assays. The effects of retinoic acid were maintained in dystrophic myoblasts derived from facioscapulohumeral patients. RT-qPCR analysis of antioxidant gene expression revealed glutathione peroxidase 3 (Gpx3), a gene encoding an antioxidant enzyme, as a potential retinoic acid target gene in human myoblasts. Knockdown of Gpx3 using short interfering RNA induced elevation in reactive oxygen species and cell death. The anti-cytotoxic effects of retinoic acid were impaired in GPx3-inactivated myoblasts, which indicates that GPx3 regulates the antioxidative effects of retinoic acid. Therefore, retinoid status and GPx3 levels may have important implications for the viability of human muscle stem cells.

Aline Hamade a, Marianne Deries a, Gerrit Begemann b, Laure Bally-Cuif c, Carine Geneˆt a, Florence Sabatier a, Anne Bonnieu a,1, Xavier Cousin a,*, Retinoic acid activates myogenesis in vivo through Fgf8 signalling Elsevier 2006

Retinoic acid (RA) has been shown to regulate muscle differentiation in vitro. Here, we have investigated the role of RA signalling during embryonic myogenesis in zebrafish. We have altered RA signalling from gastrulation stages onwards by either inhibiting endogenous RA synthesis using an inhibitor of retinaldehyde dehydrogenases (DEAB) or by addition of exogenous RA. DEAB reduces expression of the myogenic markers myoD and myogenin in somites, whereas RA induces increased expression of these genes and strongly induces premature myoD expression in the presomitic mesoderm (psm). The expression dynamics of myf5 in presomitic and somitic mesoderm suggest that RA promotes muscle differentiation, a role supported by the fact that RA activates expression of fast myosin, while DEAB represses it. We identify Fgf8 as a major relay factor in RA-mediated activation of myogenesis. We show that fgf8 expression in somites and anterior psm is regulated by RA, and find that in the absence of Fgf8 signalling in the acerebellar mutant RA fails to promote myoD expression. We propose that, in the developing embryo, localised synthesis of RA by Raldh2 in the anterior psm and in somites activates fgf8 expression which in turn induces the expression of myogenic genes and fast muscle differentiation.

Languages
Arabic

Native or bilingual proficiency

English

Full professional proficiency

French

Native or bilingual proficiency