Moshe Szyf's PublicationsLong-term effects of stress early in life on microRNA-30a and its network: Preventive effects of lurasidone and potential implications for depression vulnerability 2020-12-21Exposure to early life stress can interfere with neurodevelopmental trajectories to increase the vulnerability for psychiatric disorders later in life. With this respect, epigenetic mechanisms play a key role for the long-lasting changes in brain functions that may elicit and sustain psychopathologic outcomes. Here, we investigated DNA methylation changes as possible epigenetic mechanism mediating the […]Enhanced Anticancer Effect of a Combination of S-adenosylmethionine (SAM) and Immune Checkpoint Inhibitor (ICPi) in a Syngeneic Mouse Model of Advanced Melanoma 2020-09-28Immune checkpoint inhibitors (ICPi) targeting the PD-1/PD-L1 pathway have shown marked success in patients with advanced melanoma. However, 60-70% of patients fail to respond, warranting a therapeutic intervention that could increase response rates. We and others have shown that S-adenosylmethionine (SAM), a universal methyl donor, has significant anticancer effects in numerous cancers previously; however, its […]S-adenosylmethionine in combination with decitabine shows enhanced anti-cancer effects in repressing breast cancer growth and metastasis 2020-07-29Abnormal DNA methylation orchestrates many of the cancer-related gene expression irregularities such as the inactivation of tumour suppressor genes through hypermethylation as well as activation of prometastatic genes through hypomethylation. The fact that DNA methylation abnormalities can be chemically reversed positions the DNA methylation machinery as an attractive target for anti-cancer drug development. However, although […]An enhanced chemopreventive effect of methyl donor S-adenosylmethionine in combination with 25-hydroxyvitamin D in blocking mammary tumor growth and metastasis 2020-07-28Therapeutic targeting of metastatic breast cancer still remains a challenge as the tumor cells are highly heterogenous and exploit multiple pathways for their growth and metastatic spread that cannot always be targeted by a single-agent monotherapy regimen. Therefore, a rational approach through simultaneous targeting of several pathways may provide a better anti-cancer therapeutic effect. We […]DNA methylation signatures of Prostate Cancer in peripheral T-cells 2020-06-25CONCLUSIONS: Results from the current study provide for the first-time a potential role of DNA methylation changes in peripheral T cells in PCa. This non-invasive methodology may allow for early intervention and stratification of patients into different prognostic groups to reduce PCa associated morbidity from repeat invasive prostate biopsies and design therapeutic strategy to reduce […]DNA methylation differences in stress-related genes, functional connectivity and gray matter volume in depressed and healthy adolescents 2020-06-02CONCLUSIONS: These findings suggest that previously observed associations between SLC6A4 and FKBP5 methylation and frontolimbic processes in adult depressed patients can be in part generalized to adolescent patients. Further, findings suggest that measuring peripheral methylation at these genes deserves further attention as potential markers of typical and atypical development.The transition from acute to chronic pain: dynamic epigenetic reprogramming of the mouse prefrontal cortex up to 1 year after nerve injury 2020-05-20Chronic pain is associated with persistent structural and functional changes throughout the neuroaxis, including in the prefrontal cortex (PFC). The PFC is important in the integration of sensory, cognitive, and emotional information and in conditioned pain modulation. We previously reported widespread epigenetic reprogramming in the PFC many months after nerve injury in rodents. Epigenetic modifications, […]Prenatal S-Adenosine Methionine (SAMe) Induces Changes in Gene Expression in the Brain of Newborn Mice That Are Prevented by Co-Administration of Valproic Acid (VPA) 2020-04-25In previous studies, we produced changes in gene expression in the brain of mice by early postnatal administration of valproic acid (VPA), with distinct differences between genders. The addition of S-adenosine methionine (SAMe) normalized the expression of most genes in both genders, while SAMe alone induced no changes. We treated pregnant dams with a single […]Genome-wide DNA methylation profiling identifies two novel genes in cervical neoplasia 2020-01-27DNA methylation analysis may improve risk stratification in cervical screening. We used a pan-epigenomic approach to identify new methylation markers along the continuum of cervical intraepithelial neoplasia (CIN) to cervical cancer. Physician-collected samples (54 normal, 50 CIN1, 40 CIN2 and 42 CIN3) were randomly selected from women at a single-center colposcopy clinic. Extracted DNA was […]The epigenetics of perinatal stress 2020-01-18Early life adversity is associated with long-term effects on physical and mental health later in life, but the mechanisms are yet unclear. Epigenetic mechanisms program cell-type-specific gene expression during development, enabling one genome to be programmed in many ways, resulting in diverse stable profiles of gene expression in different cells and organs in the body. […]Preliminary indications that the Attachment and Biobehavioral Catch-up Intervention alters DNA methylation in maltreated children 2019-12-20Maltreatment during development is associated with epigenetic changes to the genome. Enhancing caregiving may mitigate these effects. Attachment and Biobehavioral Catch-Up (ABC) is an intervention that has been shown to improve parent-child relationships and a variety of biological and behavioral outcomes among children that are involved in Child Protective Services. This preliminary study, using a […]Prenatal Glucocorticoid Exposure Results in Changes in Gene Transcription and DNA Methylation in the Female Juvenile Guinea Pig Hippocampus Across Three Generations 2019-12-05Synthetic glucocorticoids (sGC) are administered to women at risk for pre-term delivery, to mature the fetal lung and decrease neonatal morbidity. sGC also profoundly affect the fetal brain. The hippocampus expresses high levels of glucocorticoid (GR) and mineralocorticoid receptor (MR), and its development is affected by elevated fetal glucocorticoid levels. Antenatal sGC results in neuroendocrine […]Prenatal maternal stress is associated with increased sensitivity to neuropathic pain and sex-specific changes in supraspinal mRNA expression of epigenetic- and stress-related genes in adulthood 2019-12-02Exposure to prenatal maternal stress impacts adult behavioral outcomes and has been suggested as a risk factor for chronic pain. However, the neurobiological mechanisms implicated are not well-characterized. In this study, we analyzed the effect of a prenatal maternal stress on the development of neuropathic pain-related behaviours and gene expression in the frontal cortex and […]Gender Related Changes in Gene Expression Induced by Valproic Acid in A Mouse Model of Autism and the Correction by S-adenosyl Methionine. Does It Explain the Gender Differences in Autistic Like Behavior? 2019-10-27In previous studies we produced autism like behavioral changes in mice by Valproic acid (VPA) with significant differences between genders. S-adenosine methionine (SAM) prevented the autism like behavior in both genders. The expression of 770 genes of pathways involved in neurophysiology and neuropathology was studied in the prefrontal cortex of 60 days old male and […]Differential genome-wide DNA methylation patterns in childhood obesity 2019-03-27OBJECTIVE: Exposure to stress during pregnancy may program susceptibility to the development of obesity in offspring. Our goal was to determine whether prenatal maternal stress (PNMS) due to a natural disaster was associated with child obesity, and to compare the DNA methylation profiles in obese versus non-obese children at age 13½ years. Women and their […]A longitudinal, epigenome-wide study of DNA methylation in anorexia nervosa: results in actively ill, partially weight-restored, long-term remitted and non-eating-disordered women 2019-01-30CONCLUSION: Findings point to the possibility of reversible epigenetic alterations in anorexia nervosa, and suggest that an adequate pathophysiological model would likely need to include psychiatric, metabolic and immune components.Antenatal Glucocorticoid Exposure Results in Sex-Specific and Transgenerational Changes in Prefrontal Cortex Gene Transcription that Relate to Behavioural Outcomes 2019-01-26Synthetic glucocorticoids (sGC) are administered to women at risk for pre-term delivery to reduce respiratory distress syndrome in the newborn. The prefrontal cortex (PFC) is important in regulating stress responses and related behaviours and expresses high levels of glucocorticoid receptors (GR). Further, antenatal exposure to sGC results in a hyperactive phenotype in first generation (F(1)) […]Fetal glucocorticoid receptor (Nr3c1) deficiency alters the landscape of DNA methylation of murine placenta in a sex-dependent manner and is associated to anxiety-like behavior in adulthood 2019-01-19Prenatal stress defines long-term phenotypes through epigenetic programming of the offspring. These effects are potentially mediated by glucocorticoid release and by sex. We hypothesized that the glucocorticoid receptor (Gr, Nr3c1) fashions the DNA methylation profile of offspring. Consistent with this hypothesis, fetal Nr3c1 heterozygosity leads to altered DNA methylation landscape in fetal placenta in a […]DRD4 methylation as a potential biomarker for physical aggression: An epigenome-wide, cross-tissue investigation 2018-11-10Epigenetic processes that regulate gene expression, such as DNA methylation (DNAm), have been linked to individual differences in physical aggression. Yet, it is currently unclear whether: (a) DNAm patterns in humans associate with physical aggression independently of other co-occurring psychiatric and behavioral symptoms; (b) whether these patterns are observable across multiple tissues; and (c) whether […]P-Glycoprotein (P-gp)/ABCB1 plays a functional role in extravillous trophoblast (EVT) invasion and is decreased in the pre-eclamptic placenta 2018-09-27Dysregulation of trophoblast differentiation is implicated in the placental pathologies of intrauterine growth restriction and pre-eclampsia. P-glycoprotein (P-gp encoded by ABCB1) is an ATP-binding cassette transporter present in the syncytiotrophoblast layer of the placenta where it acts as a molecular sieve. In this study, we show that P-gp is also expressed in the proliferating cytotrophoblast […] READ MORE THAN 300 PUBLICATIONS ON PubMed®
