Mojgan Rastegar

Mojgan Rastegar
University of Manitoba | UMN · Department of Biochemistry and Medical Genetics

PhD, DEA, MSc, BSc

About

97
Publications
22,710
Reads
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2,552
Citations
Citations since 2016
43 Research Items
1554 Citations
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
Introduction
Epigenetics, DNA methylation, Neurodevelopmental disorders, Stem cells, Brain development, Gene therapy, Rett Syndrome, Brain tumur, Transgenic mice, Drug re-purposing
Additional affiliations
April 2021 - present
University of Manitoba
Position
  • Professor (Full)
March 2015 - March 2021
University of Manitoba
Position
  • Professor (Associate)
January 2009 - March 2015
University of Manitoba
Position
  • Professor (Assistant)
Description
  • Assistant Professor
Education
September 2008 - December 2008
University of Manitoba
Field of study
  • Epigenetics
May 2000 - June 2001
Indiana University-Purdue University Indianapolis
Field of study
  • Pharmacology and Toxicology

Publications

Publications (97)
Article
DNA‐based analytical techniques have provided an advantageous sensing assay in the realm of biotechnology. Bio‐inspired fluorescent nanodots are a novel type of biological staining agent with excellent optical properties widely used for cellular imaging and diagnostics. In the present research, we successfully synthesized bio‐dots with excellent op...
Article
Eukaryotic gene expression is controlled at multiple steps that work in harmony to ensure proper maintenance of cellular morphology and function. Such regulatory mechanisms would include transcriptional gene regulation, which is in turn controlled by chromatin remodeling, distinct topologically associating domains of the chromatin structure, cis-re...
Article
Full-text available
Eukaryotic gene expression is controlled at multiple levels, including gene transcription and protein translation initiation. One molecule with key roles in both regulatory mechanisms is methyl CpG binding protein 2 (MeCP2). MECP2 gain- and loss-of-function mutations lead to Rett Syndrome and MECP2 Duplication Syndrome, respectively. To study MECP2...
Article
Gastric cancer (GC) results from deregulated cell growth in the stomach. Despite significant efforts and recent advancements in the treatment of gastric cancer, it remains a life-threatening disease. This is in part due to the chemotherapy failure resulting from multi-drug resistance (MDR) in the associated Gastric cancer cells (GCC). These cells c...
Article
Full-text available
Methyl CpG binding protein 2 (MeCP2) is the main DNA methyl-binding protein in the brain that binds to 5-methylcytosine and 5-hydroxymethyl cytosine. MECP2 gene mutations are the main origin of Rett Syndrome (RTT), a neurodevelopmental disorder in young females. The disease has no existing cure, however, metabolic drugs such as metformin and statin...
Article
Fluorescence resonance energy transfer (FRET)-based biosensors are effective analytical tools extensively used in fields of biomedicine, pharmacology, toxicology, and food sciences. Ratiometric imaging of substantial cellular processes, molecular components, and biological interactions is widely performed by these biosensors. A variety of FRET-base...
Article
Full-text available
Rett Syndrome (RTT) is a severe, rare, and progressive developmental disorder with patients displaying neurological regression and autism spectrum features. The affected individuals are primarily young females, and more than 95% of patients carry de novo mutation(s) in the Methyl-CpG-Binding Protein 2 (MECP2) gene. While the majority of RTT patient...
Article
Full-text available
Rett Syndrome (RTT) is a rare and progressive neurodevelopmental disorder that is caused by de novo mutations in the X-linked Methyl CpG binding protein 2 (MECP2) gene and is subjected to X-chromosome inactivation. RTT is commonly associated with neurological regression, autistic features, motor control impairment, seizures, loss of speech and purp...
Article
The ubiquitin proteasome system regulates key cellular processes in normal and in cancer cells. Herein, we review published data on the role of ubiquitin ligases in the four major subgroups of medulloblastoma (MB). While conventional literature serves as an initial source of information on cellular pathways in MB, large publicly available datasets...
Article
Introduction and objectives Rett Syndrome (RTT) is a neurodevelopmental disorder caused by Methyl CpG Binding Protein 2 (MECP2) gene mutations. Previous studies of MeCP2 in the human brain showed variable and inconsistent mosaic‐pattern immunolabelling, which has been interpreted as a reflection of activation‐state variability. We aimed to study po...
Article
Full-text available
Prenatal alcohol exposure (PAE) is considered as a risk factor for the development of fetal alcohol spectrum disorders (FASD). Evidence indicates that PAE affects epigenetic mechanisms (such as DNA methylation) and alters the normal differentiation and development of neural stem cells (NSC) in the fetal brain. However, PAE effects depend on several...
Article
Full-text available
Medulloblastoma is a common pediatric brain tumor and one of the main types of solid cancers in children below the age of 10. Recently, cholesterol-lowering “statin” drugs have been highlighted for their possible anti-cancer effects. Clinically, statins are reported to have promising potential for consideration as an adjuvant therapy in different t...
Article
Full-text available
Methyl CpG binding protein-2 (MeCP2) isoforms (E1 and E2) are important epigenetic regulators in brain cells. Accordingly, MeCP2 loss- or gain-of-function mutation causes neurodevelopmental disorders, including Rett syndrome (RTT), MECP2 duplication syndrome (MDS), and autism spectrum disorders (ASD). Within different types of brain cells, highest...
Article
Full-text available
We have previously reported the deregulatory impact of ethanol on global DNA methylation of brain-derived neural stem cells (NSC). Here, we conducted a genome-wide RNA-seq analysis in differentiating NSC exposed to different modes of ethanol exposure. RNA-seq results showed distinct gene expression patterns and canonical pathways induced by ethanol...
Article
Full-text available
Rett syndrome (RTT) is a severe and rare neurological disorder that is caused by mutations in the X-linked MECP2 (methyl CpG-binding protein 2) gene. MeCP2 protein is an important epigenetic factor in the brain and in neurons. In Mecp2-deficient neurons, nucleoli structures are compromised. Nucleoli are sites of active ribosomal RNA (rRNA) transcri...
Data
Primary omission control for murine cerebellum. Primary antibody omission in wild-type male and female (A,C) and mutant homozygote (B) or heterozygote (D) mice.
Data
Quantification of nuclear histone H3 and H3 di-acetylation at K9–K14 (H3AC) and cytoplasmic S100 normalized to GAPDH in Rett syndrome cerebellum and controls. (A,B) Western blot (WB) quantification of nuclear cell extracts of controls and RTT patients individually and in combination, respectively. The data are shown with the following samples in th...
Data
Detection of nucleolin protein in the cerebellum of R255X Rett syndrome (RTT) patients. (A,B) Microscopic images of post-mortem human cerebellum for nucleolin (red) and DAPI signals (white) in two female controls (a–c), and primary omission (d,e). (C,D) Microscopic images of post-mortem human cerebellum for nucleolin (red) and DAPI signals (white)...
Data
The mTOR and P70S6K signaling molecules in Rett syndrome. Representative Western blots (WB) with total cell extract of a human control and a G451T RTT cerebellum with indicated antibodies (mTOR, phosphorylated mTOR at Serine 2481 or 2448, G-Beta-L as the common component of mTOR complexes, Raptor as part of mTORC1, and Rictor as part of mTORC2), P7...
Data
Brain sample characteristics for rett syndrome (RTT) patients and controls.
Data
Secondary antibodies used for Western blot (WB) or immunohistochemistry (IHC).
Data
Primary antibodies used for Western blot (WB) or immunohistochemistry (IHC).
Chapter
Epigenetic mechanisms regulate cellular identity and organ morphology via controlling the gene expression program of specific cell types. Such mechanisms are not directly controlled by genomic DNA sequences and can be largely influenced by environmental factors. Epigenetic mechanisms include modification of DNA and DNA-bound proteins (histones), ac...
Article
Mother-infant contact has a critical role on brain development and behavior. Experiencing early-life adversities (such as maternal separation stress or MS in rodents) results in adaptations of neurotransmission systems, which may subsequently increase the risk of depression symptoms later in life. In this study, we show that Oxytocin (OT) exerted a...
Article
Adolescence is a pivotal period of brain development during lifespan, which is sensitive to stress exposure. Early social isolation stress (SIS) is known to provoke a variety of psychiatric comorbidities as well as seizure risk. Psychiatric comorbidities present challenging dilemmas for treatment and management in people with seizure disorders. In...
Chapter
Epigenetics refer to processes such as histone post-translational modifications (PTMs), DNA methylation and RNA that regulate gene activity and expression but are not dependent on alterations in DNA sequence. Herein, we review histone PTMs, histone variants and DNA modifications in the functioning of the nucleosome as an epigenetic signalling modul...
Article
Recent evidence indicates the involvement of inflammatory factors and mitochondrial dysfunction in the etiology of psychiatric disorders such as anxiety and depression. To investigate the possible role of mitochondrial-induced sterile inflammation in the co-occurrence of anxiety and depression, in this study, we treated adult male mice with the int...
Article
Early-life stress adversely affects the development of the brain, and alters a variety of behaviors such as pain in later life. In present study, we investigated how early-life stress (maternal separation or MS) can affect the nociceptive response later in life. We particularly focused on the role of oxytocin (OT) in regulating nociception in previ...
Article
Oxidative damage and aggregation of cellular proteins is a hallmark of neuronal cell death after neurotrauma and chronic neurodegenerative conditions. Autophagy and ubiquitin protease system are involved in degradation of protein aggregates, and interruption of their function is linked to apoptotic cell death in these diseases. Oxidative modificati...
Article
Amphetamine withdrawal (AW) is accompanied by diminished pleasure and depression which plays a key role in drug relapse and addictive behaviors. There is no efficient treatment for AW-induced depression and underpinning mechanisms were not well determined. Considering both transient receptor potential cation channel, subfamily V, member 1 (TRPV1) a...
Article
Tropisetron, a 5-HT3 receptor antagonist widely used as an antiemetic, has been reported to have positive effects on mood disorders. Adolescence is a critical period during the development of brain, where exposure to chronic stress during this time is highly associated with the development of depression. In this study, we showed that 4 weeks of juv...
Article
Prenatal alcohol (ethanol) exposure (PAE) is the underlying cause for a variety of birth defects and neurodevelopmental deficits referred to as "Fetal Alcohol Spectrum Disorders (FASD)". The more visible phenotypes caused by PAE include growth retardation, and characteristic craniofacial abnormalities associated with functional and structural damag...
Article
Mother-infant interactions are known to be associated with the psychological well-being of an individual in adulthood. It is well accepted that emotional stress in early life, such as maternal separation (MS), leads to alterations in the neurotransmission systems of various brain regions, especially the mesolimbic dopaminergic system, and subsequen...
Article
Methyl CpG Binding Protein 2 (MeCP2) is an important epigenetic factor in the brain. MeCP2 expression is affected by different environmental insults including alcohol exposure. Accumulating evidence supports the role of aberrant MeCP2 expression in ethanol exposure-induced neurological symptoms. However, the underlying molecular mechanisms of ethan...
Article
Full-text available
Methyl CpG Binding Protein 2 (MeCP2) is an important epigenetic factor in brain. MeCP2 expression is affected by different environmental insults including alcohol exposure. Accumulating evidence supports the role of aberrant MeCP2 expression in ethanol exposure-induced neurological symptoms. However, the underlying molecular mechanisms of ethanol-i...
Article
Methyl CpG Binding Protein 2 (MeCP2) is an important epigenetic factor in the brain. MeCP2 expression is affected by different environmental insults including alcohol exposure. Accumulating evidence supports the role of aberrant MeCP2 expression in ethanol exposure-induced neurological symptoms. However, the underlying molecular mechanisms of ethan...
Article
Full-text available
The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestr...
Chapter
Methyl CpG Binding Protein 2 (MeCP2) is an important epigenetic factor in the brain. MeCP2 expression is affected by different environmental insults including alcohol exposure. Accumulating evidence supports the role of aberrant MeCP2 expression in ethanol exposure-induced neurological symptoms. However, the underlying molecular mechanisms of ethan...
Article
Full-text available
Epigenetics refers to a variety of processes that have heritable effects on gene expression programs without changes in DNA sequence. Key players in epigenetic control are chemical modifications to DNA, histone, and non-histone chromosomal proteins, which establish a complex regulatory network that controls genome function. Methylation of DNA at th...
Article
Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT OMIM 312750). Alternative inclusion of MECP2/Mecp2 exon 1 with exons 3 and 4 encodes MeCP2-e1 or MeCP2-e2 protein isoforms with unique amino termini. While most MECP2 mutations are located in exons 3 and 4 thus affecting both isoforms, MECP2 exon 1 mutations but not exon 2...
Article
Rett syndrome (RTT) is a severe and progressive neurological disorder, which mainly affects young females. Mutations of the methyl-CpG binding protein 2 (MECP2) gene are the most prevalent cause of classical RTT cases. MECP2 mutations or altered expression are also associated with a spectrum of neurodevelopmental disorders such as autism spectrum d...
Article
Full-text available
MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of...
Article
Full-text available
The role of epigenetics in human disease has become an area of increased research interest. Collaborative efforts from scientists and clinicians have led to a better understanding of the molecular mechanisms by which epigenetic regulation is involved in the pathogenesis of many human diseases. Several neurological and non neurological disorders are...
Article
Full-text available
Epigenetics refers to a variety of processes that have heritable effects on gene expression programs without changes in DNA sequence. Key players in epigenetic control are chemical modifications to DNA, histone, and non-histone chromosomal proteins, which establish a complex regulatory network that controls genome function. Methylation of DNA at th...
Article
Full-text available
Aberrant MeCP2 expression in brain is associated with neurodevelopmental disorders including autism. In the brain of stressed mouse and autistic human patients, reduced MeCP2 expression is correlated with Mecp2/MECP2 promoter hypermethylation. Altered expression of MeCP2 isoforms (MeCP2E1 and MeCP2E2) is associated with neurological disorders, high...
Article
Full-text available
Rett Syndrome (RTT) is a severe neurological disorder in young females, and is caused by mutations in the X-linked MECP2 gene. MECP2/Mecp2 gene encodes for two protein isoforms; MeCP2E1 and MeCP2E2 that are identical except for the N-terminus region of the protein. In brain, MECP2E1 transcripts are 10X higher, and MeCP2E1 is suggested to be the rel...
Data
Controls for MeCP2 overexpression in NIH3T3 cells. A) Absence of MeCP2 and C-MYC signals in non-transfected NIH3T3 cells. B) Absence of signals in primary omission controls with Rhodamine Red and FITC in MECP2E1 transfected NIH3T3 cells. Images are taken at the same exposure time as in Figure 1E. Scale bars represent 10 µm. (TIFF)
Data
Controls to verify the specificity of MeCP2E1 immunolabelling within the adult murine brain. A) The negative control IgY did not generate any signals in Mecp2tm1.1Bird y/+ mice. B) Pre-incubation of the newly generated anti-MeCP2E1 with the antigenic peptide resulted in absence of specific labelling in Mecp2tm1.1Bird y/+ mice. Scale bars represent...
Data
Nuclear localization of MeCP2 and heterochromatin marks in primary neurons. A) MeCP2 signals in embryonic primary cortical neurons display overlapped signals with constitutive heterochromatin marks; H3K9me3 and H4K20me3. B) MeCP2 displays minimal overlap with facultative heterochromatin marks; H3K27me3 and H3K9me2. Scale bars represent 2 µm. (TIFF)
Article
The term "chromatin" was first referred to the darkly stained DNA in the nucleus in early 1880s. Over the past century, much meaning has been added to the term chromatin with regard to its structure, organization and function. During the last two decades the field of chromatin has evolved in an incredible pace with the utilization of high throughpu...
Article
Full-text available
Epigenetic changes occur throughout life from embryonic development into adulthood. This results in the timely expression of developmentally important genes, determining the morphology and identity of different cell types and tissues within the body. Epigenetics regulate gene expression and cellular morphology through multiple mechanisms without al...
Article
Full-text available
HLTF (Helicase-like Transcription Factor) is a DNA helicase protein homologous to the SWI/SNF family involved in the maintenance of genomic stability and the regulation of gene expression. HLTF has also been found to be frequently inactivated by promoter hypermethylation in human colon cancers. Whether this epigenetic event is required for intestin...
Data
Hltf -/-/Apcmin/+ mice frequently developed invasive intestinal adenocarcinomas. Several additional Haematoxylin-eosin stained images demonstrate the formation of invasive intestinal adenocarcinomas (indicated by arrows) in Hltf -/-/Apcmin/+ mice.
Data
Full-text available
List of genes that showed expression changes between Hltf +/+ and Hltf -/- mouse ES cells and in HCT116 cells with and without HLTF knockdown. The microarray expression assays were carried out by the Center for Applied Genomics at the Toronto Hospital for Sick Children. Three independent cell lines from each group were analyzed. The changes with th...
Data
Loss of Hltf function does not affect the differentiation of epithelial cells in small intestine and colon. The small intestines and colons from 2-month old Hltf +/+ and Hltf -/- mice were analyzed using several intestinal cell-lineage markers. The Goblet cells were determined by staining with Alcian blue and periodic acid-Schiff (PAS). The enteroe...
Data
Full-text available
List of PCR primers that were applied in this study.
Data
Full-text available
Loss of Hltf function does not affect the cellular proliferation in small intestine and colon. The small intestines and colons collected from 2-month old Hltf +/+ and Hltf -/- mice were stained with Haematoxylin-eosin and anti-Brdu antibody. Both Hltf +/+ and Hltf -/- intestine and colon displayed normal morphology and a similar number of BrdU posi...
Article
Full-text available
Epigenetics refer to inheritable changes beyond DNA sequence that control cell identity and morphology. Epigenetics play key roles in development and cell fate commitments and highly impact the etiology of many human diseases. A well-known link between epigenetics and human disease is the X-linked MECP2 gene, mutations in which lead to the neurolog...
Chapter
IntroductionChromatin Structure and Histone ModificationsDNA MethylationAnalyses of Epigenetic EventsEpigenetic Control of Stem Cell PluripotencyChromatin Structure in ES CellsPolycomb and Trithorax ProteinsDna Methylation and PluripotencyEpigenetics and Cellular ReprogrammingConclusion References
Article
The process of mammalian development is established through multiple complex molecular pathways acting in harmony at the genomic, proteomic, and epigenomic levels. The outcome is profoundly influenced by the role of epigenetics through transcriptional regulation of key developmental genes. Epigenetics refer to changes in gene expression that are in...
Data
Generation and maintenance of NSCs from Mecp2tm1.1Bird+/− female mice. A) Mecp2tm1.1Bird+/− female mouse displayed RTT symptoms such as hind limb clasping and small brain (inset, scale bar 5 mm). B) Neurospheres were generated from Mecp2tm1.1Bird+/− female brain. NSCs were maintained up to 21 passages for non-infected control (left), and 20 passage...
Data
NSC migration into the brain microenvironment in ex vivo culture. EGFP expressing NSCs (infected with Retro-EF1α -EGFP) were injected into brain slices of wild-type mouse, and EGFP expressing cells were detected by live imaging at the indicated days after injection. (1.46 MB EPS)
Data
MeCP2 isoforms were detected by WB in NSCs after lentiviral vector infection. NSCs were infected with indicated lentiviral vectors and whole-cell lysates were extracted from 1st sphere (1st Sph.) and 5th sphere (5th Sph.). Expression of MeCP2 isoforms was detected by WB using anti Myc-tag antibody from the EF1α promoter, but not from the MeP promot...