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233 results on '"El Hajj, Nady"'

6. Chromatin establishes an immature version of neuronal protocadherin selection during the naive-to-primed conversion of pluripotent stem cells

Author

Almenar-Queralt, Angels, Merkurjev, Daria, Kim, Hong Sook, Navarro, Michael, Ma, Qi, Chaves, Rodrigo S, Allegue, Catarina, Driscoll, Shawn P, Chen, Andrew G, Kohlnhofer, Bridget, Fong, Lauren K, Woodruff, Grace, Mackintosh, Carlos, Bohaciakova, Dasa, Hruska-Plochan, Marian, Tadokoro, Takahiro, Young, Jessica E, El Hajj, Nady, Dittrich, Marcus, Marsala, Martin, Goldstein, Lawrence SB, and Garcia-Bassets, Ivan

Subjects
Biological Sciences, Genetics, Pediatric, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research - Nonembryonic - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Embryonic - Human, Neurosciences, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Adult, Animals, Astrocytes, Brain, Cadherins, Cell Differentiation, Cell Line, Chromatin, Down Syndrome, Gene Expression Regulation, Histones, Humans, Induced Pluripotent Stem Cells, Mice, Middle Aged, Neurons, Promoter Regions, Genetic, Rats, Single-Cell Analysis, Spinal Cord, Transplantation, Heterologous, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

In the mammalian genome, the clustered protocadherin (cPCDH) locus provides a paradigm for stochastic gene expression with the potential to generate a unique cPCDH combination in every neuron. Here we report a chromatin-based mechanism that emerges during the transition from the naive to the primed states of cell pluripotency and reduces, by orders of magnitude, the combinatorial potential in the human cPCDH locus. This mechanism selectively increases the frequency of stochastic selection of a small subset of cPCDH genes after neuronal differentiation in monolayers, 10-month-old cortical organoids and engrafted cells in the spinal cords of rats. Signs of these frequent selections can be observed in the brain throughout fetal development and disappear after birth, except in conditions of delayed maturation such as Down's syndrome. We therefore propose that a pattern of limited cPCDH-gene expression diversity is maintained while human neurons still retain fetal-like levels of maturation.

Published
2019

10. DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma

Author

Chehade, Georges, primary, El Hajj, Nady, additional, Aittaleb, Mohamed, additional, Alkailani, Maisa I., additional, Bejaoui, Yosra, additional, Mahdi, Asma, additional, Aldaalis, Arwa A. H., additional, Verbiest, Michael, additional, Lelotte, Julie, additional, Ruiz-Reig, Nuria, additional, Durá, Irene, additional, Raftopoulos, Christian, additional, Tajeddine, Nicolas, additional, and Tissir, Fadel, additional

Published
2024
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11. DIAPH3 predicts survival of patients with MGMT-methylated glioblastoma

Author

Chehade, Georges, El Hajj, Nady, Aittaleb, Mohamed, Alkailani, Maisa I., Bejaoui, Yosra, Mahdi, Asma, Aldaalis, Arwa A. H., Verbiest, Michael, Lelotte, Julie, Ruiz-Reig, Nuria, Dura, Irene, Raftopoulos, Christian, Tajeddine, Nicolas, Tissir, Fadel, Chehade, Georges, El Hajj, Nady, Aittaleb, Mohamed, Alkailani, Maisa I., Bejaoui, Yosra, Mahdi, Asma, Aldaalis, Arwa A. H., Verbiest, Michael, Lelotte, Julie, Ruiz-Reig, Nuria, Dura, Irene, Raftopoulos, Christian, Tajeddine, Nicolas, and Tissir, Fadel

Abstract

Background: Glioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors. Methods: We analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient's survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach. Results: We found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient's survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region. Conclusion: We propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma.

Published
2024

14. The impact of COVID-19 on "biological aging".

Author

Amanullah, Fathima Humaira, Alam, Tanvir, El Hajj, Nady, and Bejaoui, Yosra

Subjects
COVID-19 pandemic, HIV, COVID-19, AGE, BIOMARKERS
Abstract

The global impact of the SARS-CoV-2 pandemic has been unprecedented, posing a significant public health challenge. Chronological age has been identified as a key determinant for severe outcomes associated with SARS-CoV-2 infection. Epigenetic age acceleration has previously been observed in various diseases including human immunodeficiency virus (HIV), Cytomegalovirus (CMV), cardiovascular diseases, and cancer. However, a comprehensive review of this topic is still missing in the field. In this review, we explore and summarize the research work focusing on biological aging markers, i.e., epigenetic age and telomere attrition in COVID-19 patients. From the reviewed articles, we identified a consistent pattern of epigenetic age dysregulation and shortened telomere length, revealing the impact of COVID-19 on epigenetic aging and telomere attrition. [ABSTRACT FROM AUTHOR]

Published
2024
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18. DIAPH3 predicts survival of patients with MGMTmethylated glioblastoma

Author

Chehade, Georges, El Hajj, Nady, Aittaleb, Mohamed, Alkailani, Maisa I., Bejaoui, Yosra, Mahdi, Asma, Aldaalis, Arwa A. H., Verbiest, Michael, Lelotte, Julie, Ruiz-Reig, Nuria, Durá, Irene, Raftopoulos, Christian, Tajeddine, Nicolas, and Tissir, Fadel

Abstract

Background: Glioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors. Methods: We analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient’s survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach. Results: We found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient’s survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region. Conclusion: We propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Methylomic profiling in trisomy 21 identifies cognition- and Alzheimer’s disease-related dysregulation

Author

Haertle, Larissa, Müller, Tobias, Lardenoije, Roy, Maierhofer, Anna, Dittrich, Marcus, Riemens, Renzo J. M., Stora, Samantha, Roche, Mathilde, Leber, Markus, Riedel-Heller, Steffi, Wagner, Michael, Scherer, Martin, Ravel, Aimé, Mircher, Clotilde, Cieuta-Walti, Cecile, Durand, Sophie, van de Hove, Daniel L. A., Hoffmann, Per, Ramirez, Alfredo, Haaf, Thomas, El Hajj, Nady, and Mégarbané, André

Published
2019
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23. Accelerated epigenetic aging and DNA methylation alterations in Berardinelli–Seip congenital lipodystrophy

Author

Qannan, Abeer, primary, Bejaoui, Yosra, additional, Izadi, Mahmoud, additional, Yousri, Noha A, additional, Razzaq, Aleem, additional, Christiansen, Colette, additional, Martin, George M, additional, Bell, Jordana T, additional, Horvath, Steve, additional, Oshima, Junko, additional, Megarbane, Andre, additional, Ericsson, Johan, additional, Pourkarimi, Ehsan, additional, and El Hajj, Nady, additional

Published
2023
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25. DNA methylation profiling in Trisomy 21 females with and without breast cancer.

Author

Bejaoui, Yosra, Alresheq, Sara, Durand, Sophie, Vilaire-Meunier, Marie, Maillebouis, Louise, Zen, Ayman Al Haj, Mégarbané, André, and El Hajj, Nady

Subjects
DNA methylation, DOWN syndrome, BREAST cancer, ACUTE myeloid leukemia, CHROMOSOME abnormalities, OCCLUDINS, CD19 antigen
Abstract

Background: Down Syndrome (DS) is the most common chromosome anomaly in humans and occurs due to an extra copy of chromosome 21. The malignancy profile in DS is unique, since DS patients have a low risk of developing solid tumors such as breast cancer however they are at higher risk of developing acute myeloid leukemia and acute lymphoblastic leukemia. Methods: In this study, we investigated DNA methylation signatures and epigenetic aging in DS individuals with and without breast cancer. We analyzed DNA methylation patterns in Trisomy 21 (T21) individuals without breast cancer (T21-BCF) and DS individuals with breast cancer (T21-BC), using the Infinium Methylation EPIC BeadChip array. Results: Our results revealed several differentially methylated sites and regions in the T21-BC patients that were associated with changes in gene expression. The differentially methylated CpG sites were enriched for processes related to serinetype peptidase activity, epithelial cell development, GTPase activity, bicellular tight junction, Ras protein signal transduction, etc. On the other hand, the epigenetic age acceleration analysis showed no difference between T21-BC and T21-BCF patients. Conclusions: This is the first study to investigate DNA methylation changes in Down syndrome women with and without breast cancer and it could help shed light on factors that protect against breast cancer in DS. [ABSTRACT FROM AUTHOR]

Published
2023
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29. DNA methylation signatures in Blood DNA of Hutchinson–Gilford Progeria syndrome

Author

Bejaoui, Yosra, primary, Razzaq, Aleem, additional, Yousri, Noha A., additional, Oshima, Junko, additional, Megarbane, Andre, additional, Qannan, Abeer, additional, Potabattula, Ramya, additional, Alam, Tanvir, additional, Martin, George M., additional, Horn, Henning F., additional, Haaf, Thomas, additional, Horvath, Steve, additional, and El Hajj, Nady, additional

Published
2022
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32. Increasing methylation of sperm rDNA and other repetitive elements in the aging male mammalian germline

Author

Potabattula, Ramya, primary, Zacchini, Federica, additional, Ptak, Grazyna Ewa, additional, Dittrich, Marcus, additional, Müller, Tobias, additional, El Hajj, Nady, additional, Hahn, Thomas, additional, Drummer, Charis, additional, Behr, Rüdiger, additional, Lucas‐Hahn, Andrea, additional, Niemann, Heiner, additional, Schorsch, Martin, additional, and Haaf, Thomas, additional

Published
2020
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37. Genome‐wide DNA methylation analysis of colorectal adenomas with and without recurrence reveals an association between cytosine‐phosphate‐guanine methylation and histological subtypes

Author

Fiedler, David, primary, Hirsch, Daniela, additional, El Hajj, Nady, additional, Yang, Howard H., additional, Hu, Yue, additional, Sticht, Carsten, additional, Nanda, Indrajit, additional, Belle, Sebastian, additional, Rueschoff, Josef, additional, Lee, Maxwell P., additional, Ried, Thomas, additional, Haaf, Thomas, additional, and Gaiser, Timo, additional

Published
2019
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39. The DNA methylation profile of human spermatogonia at single-cell- and single-allele-resolution refutes its role in spermatogonial stem cell function and germ cell differentiation

Author

Fend-Guella, Desiree Lucia, primary, von Kopylow, Kathrein, additional, Spiess, Andrej-Nikolai, additional, Schulze, Wolfgang, additional, Salzbrunn, Andrea, additional, Diederich, Stefan, additional, El Hajj, Nady, additional, Haaf, Thomas, additional, Zechner, Ulrich, additional, and Linke, Matthias, additional

Published
2019
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40. Cell Type and Species-specific Patterns in Neuronal and Non-neuronal Methylomes of Human and Chimpanzee Cortices

Author

Böck, Julia, primary, Remmele, Christian W, additional, Dittrich, Marcus, additional, Müller, Tobias, additional, Kondova, Ivanela, additional, Persengiev, Stephan, additional, Bontrop, Ronald E, additional, Ade, Carsten P, additional, Kraus, Theo F J, additional, Giese, Armin, additional, El Hajj, Nady, additional, Schneider, Eberhard, additional, and Haaf, Thomas, additional

Published
2018
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41. 183-P

Author

Khalaf, Roy A., Rayes, Roni, Ghasham, Mona, El Hajj, Nady, Sabbagh, Amira S., Mahfouz, Rami A., Khalaf, Roy A., Rayes, Roni, Ghasham, Mona, El Hajj, Nady, Sabbagh, Amira S., and Mahfouz, Rami A.

Abstract

Aim: This study represents the first report on KIR distribution among patients with Familial Mediterranean Fever (FMF). Samples and Methods: We studied 56 unrelated Lebanese FMF patients, had their DNA typed using Sequence Specific Primer (SSP) technique for the presence of 16 KIR gene and pseudogene loci and compared them to the general Lebanese population. Results: In addition to sharing common features with the general population, we the AA genotype was still the most frequent; however, with six new KIR profiles identified. Conclusions: There was no statistically significant distribution of the different KIR genes between the cases (FMF patients) and controls (Lebanese population); however, an increase in the BB genotype was noted leading to an interesting future research question of whether or not KIR genotype is involved in the predisposition to or pathogenesis of FMF. This is the first report that describes the KIR genotypic profile in this important clinical disease.

Published
2018

46. Natural Killer Cell Immunoglobulin-like Receptor (KIR) genotypes in Follicular Lymphoma patients

Author

Khalaf, Roy, Hoteit, Rouba, Yazbek, Soha, El Hajj, Nady, Otrock, Zaher, Khansa, Sarah, Sabbagh, Amira, Shammaa, Dina, Mahfouz, Rami, Khalaf, Roy, Hoteit, Rouba, Yazbek, Soha, El Hajj, Nady, Otrock, Zaher, Khansa, Sarah, Sabbagh, Amira, Shammaa, Dina, and Mahfouz, Rami

Abstract

Aims The Natural Killer Cell Immunoglobulin-like Receptor (KIR) genotype profiling in Follicular Lymphoma has not been reported before in the literature. Materials and methods DNA extracted from 20 Follicular Lymphoma patients and 62 healthy controls was analyzed for KIR genotyping using a polymerase chain reaction/sequence specific primers technique (PCR/SSP) for the presence of 16 KIR gene and pseudogene loci. Results The AA, AB, and BB genotype frequencies were, respectively, 20%, 60% and 20% with an A:B ratio of 1:1. KIR 2DL4, KIR 3DL2, KIR 3DL3, and KIR 3DP1*003 were presented in all individuals. No significant difference between patients and controls was detected. Conclusion KIR genotyping profile does not seem to be associated with Follicular Lymphoma. The results presented in this pilot research represent the first international report about this important clinical entity. Abbreviations KIR, Killer Cell Immunoglobulin-like Receptors; PCR, Polymerase chain reaction; SSP, Sequence specific primers; NHL, Non-Hodgkin's lymphoma; Ig, Immunoglobulin; FL, Follicular Lymphoma; NK, Natural killer; HLA, Human leukocyte antigens; MHC, Major histocompatibility complex; ITIM, Immunoreceptor tyrosine based inhibition motifs; HSTCL, Hepatosplenic T-cell lymphoma; UV, Ultraviolet

Published
2016

47. Killer Cell Immunoglobulin-Like Receptor (KIR) Genotypes in Patients with Recurrent Tonsillitis

Author

Khalaf, Roy, Bitar, Mohamad, Shamseddeen, Wael, El Hajj, Nady, Ibrahim, Georges, Greige, Layal, Zaatari, Ghazi, Khalaf, Roy, Bitar, Mohamad, Shamseddeen, Wael, El Hajj, Nady, Ibrahim, Georges, Greige, Layal, and Zaatari, Ghazi

Abstract

Aims: This study represents the first report on the distribution of killer cell immunoglobulin-like receptor (KIR) genotype among recurrent tonsillitis patients. We recruited 34 Lebanese pediatric patients diagnosed with recurrent tonsillitis and had their DNA typed using sequence-specific primer technique for the presence of 16 KIR loci. Results: We observed that 25 different KIR genotypes were present similar to the general control population with the same KIR gene content. There was no statistically significant difference in the distribution of the activating and inhibitory KIR genes between the two categories. Like in the general control population, we noted a predominance of the AB genotype; however, the KIR genotypic distribution among the tonsillitis patients was much more heterogeneous with even new genotypes not reported in the control group. Conclusions: Although the sample size is small, this first study observes an interesting heterogeneous KIR gene profile in recurrent tonsillitis that warrants larger and further research in the area for the true biological and clinical significance of this observation.

Published
2016

50. Epigenetic dysregulation in the developing Down syndrome cortex

Author

El Hajj, Nady, primary, Dittrich, Marcus, additional, Böck, Julia, additional, Kraus, Theo F. J., additional, Nanda, Indrajit, additional, Müller, Tobias, additional, Seidmann, Larissa, additional, Tralau, Tim, additional, Galetzka, Danuta, additional, Schneider, Eberhard, additional, and Haaf, Thomas, additional

Published
2016
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