User talk:Ericmilou

Education[edit]

He holds a PhD in Genetics and Molecular Biology from the University of Montpellier, Medical School (France).

Career[edit]

For over 8 years between 2004 and 2012, Dr. Ezzeddine worked in two different Universities such as Einstein, College of Medicine NYC and the University of Texas Medical School at Houston, in many divers project touching the RNA and their implication in different human diseases as Cancer. In 2012, Dr. Ezzeddine was recruited to the Institute for Personalized Cancer Therapy (IPCT), The University of Texas MD Anderson Cancer Center, as Research Scientist, to develop the Next generation Sequencing and the RNAseq technology to explore the genetic changes and their consequences at the DNA and RNA levels in cancer patients at MD Anderson. Over the span of his career, Dr. Ezzeddine has been the center of a long list of funded research projects of a wide variety of subjects in France and the United States. With 11 publications, Dr. Ezzeddine has authored papers in such prestigious journals as Proceedings of the National Academy of Sciences, Molecular Cell Biology, Journal of Cell Biol, Nucleic Acids, RNA… Dr. Ezzeddine has made significant contributions to the understanding of RNA stability and its contribution to several diseases such as cancer and other genetic diseases.

Here we’re going to develop some of his major projects over his career: 1998- 2003: Dr. Ezzeddine earned his Master and Ph.D. degrees from The University of the Mediterranean (Marseille) and the University of Montpellier I, College of medicine (Montpellier) in France. During these 5 years Dr. Ezzeddine was working on has been dedicated to an analysis of post-transcriptional regulation in Drosophila. At a specific time of the animal development, the expression of some mRNA is highly regulated by different elements located on the 3’UTR. At the maturation of the oocyte of the Xenopus, an element called the CPE (Cytoplasmic Polyadenylation Element) induces a translation activation of the mRNA after an elongation of the poly(A) tail on the 3’UTR. At the fertilization, there is a second element also located on the 3’UTR, called EDEN (Embryonic Deadenylation ElemeNt) UG/UA rich, but this sequence induces a translation repression after removing the poly(A) tail of the messenger. In this part, I have shown that the mechanism of EDEN element is conserved between Drosophila and Xenopus. For that, I cloned the Xenopus element downstream a b-galactosidase ORF into Drosophila and I generate a transgenic flies carrying EDEN element. I then checked the expression of the galactosidase by Western blot and X-gal staining and the stability of the reporter mRNA by Northern blot and in-situ hybridization. These experiments demonstrated that the mechanism of EDEN element is conserved between Xenopus and Drosophila. After that, I identified the Drosophila protein that binds EDEN element and we called it Bru-3 because of its homology with Bruno protein, and I proved it by gel shift and cross link experiments. This work has been published in “PNAS” where I was first author and in “Nucl Acids” where I was second author. 2004- 2005: At Albert Einstein College of Medicine of Yeshiva University (NYC)                             Department of Cardiology, working with Dr. Hanh Thi Nguyen, currently a Group Leader at the Dept. of Biology (Div. of Developmental Biology), University of Erlangen-Nürnberg, Erlangen. The main project was to study the generation and maintenance of functional skeletal and visceral muscles. In particular, they were using a combination of cellular, genetic and molecular approaches to define novel components and pathways that control the critical events in muscle formation and morphogenesis in the Drosophila embryo. In recent studies, they determined that the mind bomb 2 (mib2) gene, which codes for a protein with Ankyrin repeats and RING fingers, is critical for the survival of differentiated muscle fibers. In mib2 Drosophila mutant embryos, muscles are formed normally however they undergo detachment and apoptosis during late stages of embryogenesis.

2005- 2011: At the University of Texas Medical School at Houston, Department of Biochemistry & Molecular Biology. Project 1: Studying the mRNA stability in mammalian cells with Dr. Ann-Bin Shyu, currently Chair in Molecular Biology at the University of Texas Medical School at Houston. This work was divided into two essential parts. First part: I demonstrated that deadenylation is required for mammalian P-bodies formation and mRNA decay. By immunoprecipitation I showed that Pan2-Pan3 and Ccr4-Caf1 complexes interact with each other in-vivo. By Northern blot, I showed that Caf1 is required for deadenylation and can accelerate poly(A) shortening in mouse NIH3T3 cells. And finally, I showed that knocking down Caf1 or overexpressing a Caf1 catalytically inactive mutant impairs deadenylation and mRNA decay. This work has been published in “J Cell Biol” and I was co first author. Second part: In this work I showed that TOB, an anti-proliferative protein, capable to bind both poly(A)-binding-protein (PABP) and CAF1 simultaneously, enhances mammalian mRNA deadenylation in a PABP dependent manner. To further elucidate the mechanism by which TOB regulates deadenylation, I performed experiments to address the role of CAF1 in TOB-promoted deadenylation. Combining the transcriptional pulsing approach, the MS2-tethering strategy, and siRNA-mediated knockdown, I found that the deadenylation enhancing effect of TOB proteins requires CAF1. These results suggest that TOB promotes deadenylation through its interaction with the poly(A)-PABP complex by recruiting poly(A) nucleases, such as CCR4-CAF1, to the 3' poly(A) tail of an mRNA. This work is published in “Mol Cell Biol” where I was first author. Also another paper has been submitted in Mol Cell Biol. Project 2: Studying the snRNA biogenesis with Dr. Eric Wagner, currently Assistant Professor at the University of Texas Medical School at Houston. The work was focusing on small nuclear RNA and their implication in different human diseases using Drosophila as model study. The vast majority of human genes contain introns and that most pre-mRNAs undergo alternative splicing through the splicesome complex which contain up to 5 UsnRNA and over 100 proteins. It is essential for the cell to carry out precise snRNA processing as aberrant snRNAs may ultimately impact the fidelity of the spliceosome and lead to problems in gene expression. It is not surprising that disruption of normal splicing patterns can cause or modify human disease. During this work, Dr. Ezzeddine showed that IntS1 and IntS4 with IntS9 and IntS11 are the major important subunit of the Integrator complex in Drosophila; a complex required for the spliceosomal snRNA 3’ End Formation. Dr. Ezzeddine used the technology that Dr Wagner developed based on a cell reporter that monitors the 3’ end formation of snRNA in Drosophila cells through the gain in expression of GFP. So Dr. Ezzeddine used this reporter to determine requirements for U7 snRNA 3’ end formation and he find that not all of the biochemically purified Integrator subunits are required for U7 snRNA biosynthesis and that four subunits in particular are most critical. Moreover, depletion of Integrator proteins using RNAi in S2 cells results in significant increase in the levels of endogenous misprocessed spliceosomal snRNAs. Finally, Drosophila harboring a deletion of the Integrator 7 gene or P-element insertion within the Integrator 4 gene are both lethal at the third instar larval stage and have significantly increased levels of misprocessed snRNAs. This work has been published in “Moll Cell Bio” as well. Recently, Dr. Ezzeddine published a new fantastic work in RNA journal, titled An RNAi screen identifies additional members of the Drosophila Integrator complex and a requirement for cyclin C/Cdk8 in snRNA 3'-end formation.

20011- 2012: At the University of Texas Medical School at Houston, Department of Internal medicine, working with Dr. Xiaodong Zhou, currently Associate Professor at the Department of Internal Medicine, on a new exciting project to Reprogram Fibroblasts cells from Scleroderma patients into iPS Stem Cells. The work was focusing on the vasculopathy which is an early and major pathological feature of scleroderma. It significantly contributes to morbidity and mortality of SSC patients. Endothelial damage with defects in the neovascularization and vessel repair has been a major challenge in the treatment of SSC. Recent advent of human induced pluripotent stem (iPS) cell technologies enables generation of endothelial cells by reprogramming somatic cells, which is a major breakthrough in potential application of stem cell therapy for the treatment of vasculopathy. However before potential clinical application of iPS cells, Dr. Ezzeddine found the necessary to develop a safe and efficient method for use of iPS cells. Currently, commonly used methods for the induction of iPS cells rely on the use of viral vectors to express embryonic genes, which have risks of insertional mutagenesis and transgene reactivity. Dr. Ezzeddine work was dedicated to develop a new technique, viral free to reprogram human fibroblasts cells from skin biopsies of Scleroderma patients into iPS cells that can be further differentiated into endothelial cells. The methods that I am developing in the laboratory require DNA or RNA transfection of the fibroblasts cells, by expressing the embryonic genes Oct4, Sox2, Klf4, c-Myc, Lin28 and Nanog.

2012- present: At the Institute for Personalized Cancer Therapy (IPCT) at MD Anderson, working with Dr. Gordon Mills, Co-Director of the IPCT, Professor of Medicine and Immunology and Chair of the Department of Systems Biology at MD Anderson. This Center holds the responsibility for developing personalized molecular medicine at the MD Anderson Cancer Center. Specifically, this center will implement a series of novel technologies to for the first time, explore the genetic changes and their consequences at the DNA, RNA and protein levels in human tumors. This information will be used to identify patients at high risk for tumor development so they can be triaged to early screening and chemoprevention, identify markers to use in early screening, and to determine approaches to ensure that patients receive the most effective and least toxic therapies targeting the underlying genetic aberrations in tumors.

Ways to improve Nader Ezzedine
Hi, I'm Jbhunley. Ericmilou, thanks for creating Nader Ezzedine!

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Proposed deletion of Nader Ezzedine
Hello, Ericmilou. I wanted to let you know that I’m proposing an article that you started, Nader Ezzedine, for deletion because it's a biography of a living person that lacks references. If you don't want Nader Ezzedine to be deleted, please add a reference to the article.

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Nomination of Nader Ezzeddine for deletion
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