Moshe Szyf's PublicationsValidation of novel DNA methylation markers in cervical precancer and cancer 2023-08-22We have recently identified, using a genome-wide approach, new methylation markers which were evaluated among various cervical intraepithelial neoplasia (CIN) grades and cervical cancer. We herein validate the methylated state of these genes in independent study populations, based on histology ascertained outcomes regardless of human papillomavirus status. CA10, DPP10, FMN2 and HAS1 (discovery set: 54 […]Methyl-CpG binding domain 2 (Mbd2) is an epigenetic regulator of autism-risk genes and cognition 2023-07-13The Methyl-CpG-Binding Domain Protein family has been implicated in neurodevelopmental disorders. The Methyl-CpG-binding domain 2 (Mbd2) binds methylated DNA and was shown to play an important role in cancer and immunity. Some evidence linked this protein to neurodevelopment. However, its exact role in neurodevelopment and brain function is mostly unknown. Here we show that Mbd2-deficiency […]A high-throughput test enables specific detection of hepatocellular carcinoma 2023-06-07High-throughput tests for early cancer detection can revolutionize public health and reduce cancer morbidity and mortality. Here we show a DNA methylation signature for hepatocellular carcinoma (HCC) detection in liquid biopsies, distinct from normal tissues and blood profiles. We developed a classifier using four CpG sites, validated in TCGA HCC data. A single F12 gene […]Increasing Specificity of Targeted DNA Methylation Editing by Non-Enzymatic CRISPR/dCas9-Based Steric Hindrance 2023-05-27As advances in genome engineering inch the technology towards wider clinical use-slowed by technical and ethical hurdles-a newer offshoot, termed "epigenome engineering", offers the ability to correct disease-causing changes in the DNA without changing its sequence and, thus, without some of the unfavorable correlates of doing so. In this review, we note some of the […]The PROTECTOR strategy employs dCas orthologs to sterically shield off-target sites from CRISPR/Cas activity 2023-02-09Off-target mutagenesis of CRISPR/Cas systems must be solved to facilitate safe gene therapy. Here, we report a novel approach, termed "PROTECTOR", to shield known off-target sites by directing the binding of an orthologous nuclease-dead Cas protein to the off-target site to sterically interfere with Cas activity. We show that this method reduces off-target mutation rates […]S-adenosylmethionine blocks tumorigenesis and with immune checkpoint inhibitor enhances anti-cancer efficacy against BRAF mutant and wildtype melanomas 2023-01-13Despite marked success in treatment with immune checkpoint inhibitor (CPI), only a third of patients are responsive. Thus, melanoma still has one of the highest prevalence and mortality rates; which has led to a search for novel combination therapies that might complement CPI. Aberrant methylomes are one of the mechanisms of resistance to CPI therapy. […]Co-Targeting Luminal B Breast Cancer with S-Adenosylmethionine and Immune Checkpoint Inhibitor Reduces Primary Tumor Growth and Progression, and Metastasis to Lungs and Bone 2023-01-08Breast cancer (BCa) is the most prevalent cancer in females and has a high rate of mortality, especially due to increased metastasis to skeletal and non-skeletal sites. Despite the marked clinical accomplishment of immune checkpoint inhibitor (CPI) therapy in patients with several cancers, it has had limited success in luminal subtypes of BCa. Accordingly, recent […]Enzyme-free targeted DNA demethylation using CRISPR-dCas9-based steric hindrance to identify DNA methylation marks causal to altered gene expression 2022-10-07DNA methylation involves the enzymatic addition of a methyl group primarily to cytosine residues in DNA. This protocol describes how to produce complete and minimally confounded DNA demethylation of specific sites in the genome of cultured cells by clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9 and without the involvement of an epigenetic-modifying enzyme, the purpose […]Author Correction: [<sup>11</sup>C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer's disease 2022-10-03No abstractThe role of DNA demethylation in liver to pancreas transdifferentiation 2022-09-16CONCLUSIONS: Transdifferentiation is associated with global DNA hypomethylation, and with increased expression of specific demethylated genes. A combination of epigenetic modulators may be used to increase chromatin accessibility of the pancreatic transcription factors, thus promoting the efficiency of the developmental process.Epigenetic perspectives of COVID-19: Virus infection to disease progression and therapeutic control 2022-08-24COVID-19 has caused numerous deaths as well as imposed social isolation and upheaval world-wide. Although, the genome and the composition of the virus, the entry process and replication mechanisms are well investigated from by several laboratories across the world, there are many unknown remaining questions. For example, what are the functions of membrane lipids during […]Correction for: Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial 2022-07-30No abstract[<sup>11</sup>C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer's disease 2022-07-19Alzheimer's disease (AD) is characterized by the brain accumulation of amyloid-β and tau proteins. A growing body of literature suggests that epigenetic dysregulations play a role in the interplay of hallmark proteinopathies with neurodegeneration and cognitive impairment. Here, we aim to characterize an epigenetic dysregulation associated with the brain deposition of amyloid-β and tau proteins. […]Modulation of DNA methylation and protein expression in the prefrontal cortex by repeated administration of D-lysergic acid diethylamide (LSD): Impact on neurotropic, neurotrophic, and neuroplasticity signaling 2022-07-01CONCLUSIONS: LSD affects DNA methylation, altering gene expression and protein expression related to neurotropic-, neurotrophic- and neuroplasticity signaling. This could represent a core mechanism mediating the effects of psychedelics.DNA methylation in people with anorexia nervosa: Epigenome-wide patterns in actively ill, long-term remitted, and healthy-eater women 2022-06-15CONCLUSIONS: Findings corroborate earlier results suggesting reversible DNA methylation alterations in AN, and point to particular genes at which epigenetic mechanisms may act to shape AN phenomenology.Building knowledge, optimising physical and mental health and setting up healthier life trajectories in South African women (<em>Bukhali</em>): a preconception randomised control trial part of the Healthy Life Trajectories Initiative (HeLTI) 2022-04-22INTRODUCTION: South Africa's evolving burden of disease is challenging due to a persistent infectious disease, burgeoning obesity, most notably among women and rising rates of non-communicable diseases (NCDs). With two thirds of women presenting at their first antenatal visit either overweight or obese in urban South Africa (SA), the preconception period is an opportunity to […]Corrigendum to "Pharmacological inhibition of DNA methylation induces proinvasive and prometastatic genes in vitro and in vivo" [Neoplasia 10/3 (2008) 266-278] 2022-04-02No abstractThe epigenetics of early life adversity and trauma inheritance: an interview with Moshe Szyf 2021-12-08In this interview, Professor Moshe Szyf speaks with Storm Johnson, Commissioning Editor for Epigenomics, on his work to date in the field of social epigenetics. Szyf received his PhD from the Hebrew University and did his postdoctoral fellowship in genetics at Harvard Medical School, joined the Department of Pharmacology and Therapeutics at McGill University in […]Epigenetic signature of chronic low back pain in human T cells 2021-11-08CONCLUSION: This study reveals sex-specific DNA methylation signatures in human T cells that discriminates chronic LBP participants from healthy controls.Unraveling the functional role of DNA demethylation at specific promoters by targeted steric blockage of DNA methyltransferase with CRISPR/dCas9 2021-09-30Despite four decades of research to support the association between DNA methylation and gene expression, the causality of this relationship remains unresolved. Here, we reaffirm that experimental confounds preclude resolution of this question with existing strategies, including recently developed CRISPR/dCas9 and TET-based epigenetic editors. Instead, we demonstrate a highly effective method using only nuclease-dead Cas9 […] READ MORE THAN 300 PUBLICATIONS ON PubMed®
