P. Casaccia
Advanced Science Research Center at GC-CUNY NeurosciencePatrizia Casaccia trained at Cornell Weill Medical Center and at the Skirball Institute at NYU, after receiving her MD in Rome and PhD from SUNY. She joined Rutgers University Medical School as Assistant Professor and later moved to Icahn School of Medicine at Mount Sinai, where she was member of the Leadership team of the Friedman Brain Institute and Professor of Genomics and Neurology. She retains an affiliation with the Medical School as Professor of Neuroscience and Co-Director of the Inter-Institutional CUNY-Mount Sinai Center for Glial Biology. In August 2016 she moved to CUNY to direct the Neuroscience Initiative at the ASRC. Dr. Casaccia’s work adopts molecular and cellular techniques to study the effect of environmental and lifestyle variables on brain health, with an emphasis on epigenomics, lipidomics and metabolomics as tools for regenerative strategies. Dr. Casaccia has been the recipient of several awards, including the Excellence in Teaching for Medical Students, the Master Educator Medal for Excellence in Graduate Education, the US congressionally mandated 2012 Javits Investigator Merit Award in Neuroscience and the NIH 2019 Outstanding Investigator Award from the National Institute of Neurological Disorders and Stroke. Currently she serves on several National and International grant review and programmatic panels and maintains a vibrant research program and commitment to development and training of young scientists.
Author Of 1 Presentation
PS08.01 - The Epigenome and Multiple Sclerosis
Abstract
Abstract
Epigenome in Multiple Sclerosis
P. Casaccia1,2; K. Castro1; A. Ntranos3; S. Moyon1; B. Inbar1D.; Marechal1; I. Katz Sand3
1Neuroscience Initiative, CUNY Advanced Science Research Center at The Graduate Center, New York, NY; 2Neuroscience, 3Neurology, Icahn School of Medicine at Mount Sinai, New York, NY
Background: Multiple Sclerosis results from the interaction of genetic predisposition and environmental exposure. Epigenetics refers to the molecular mechanisms by which cells “interpret” external signals, and modulate gene expression. These mechanisms are unique for each cell type and age-dependent. This presentation is focused on DNA methylation.
Objectives: We previously reported differences in the genome-wide distribution of DNA methylation in the normal appearing white matter in post-mortem brains from Multiple Sclerosis patients compared to healthy controls. We generated a mouse model to test the functional relevance of those genes initially identified as hypermethylated in MS brains. In addition, I will review our epigenomic studies conducted in peripheral cells isolated from peripheral blood of RRMS patients.
Methods: DNA methylation was conducted using Illumina bead chip on monocytes from 54 relapsing-remitting therapy-naïve female patients with low or high body mass and in CD4+ lymphocytes, from 47 therapy naive patients, 35 on dimethylfumarate (DMF) and 16 glatiramer acetate (GA) . Functional characterization of novel mouse models generated to test the functional relevance of genes hypermethylated in MS brains will be presented.
Results: DNA methylation in monocytes from RRMS patients differed between high and low BMI groups. Functionally, high BMI correlated with high ceramide levels which induced DNA hypermethylation, affected gene expression and increased the number of circulating monocytes. In patients at the 2 year follow up, the high BMI group showed worsening disability, an effect that could be reproduced in animal models. The study in CD4+ lymphocytes, highlighted the effect of DMF on hypermethylation on the microRNA MIR- 21, which is critical for the differentiation of T helper-17 cells.
Conclusions: External factors, such as disease state, BMI or therapy, affect the behavior of distinct cell types by creating cell-specific DNA methylation patterns in the CNS and in the periphery. These epigenomic changes impact T cell differentiation, modulate the number of circulating monocytes and also affect the ability of oligodendrocyte progenitors to form new myelin after demyelination. Together with additional ongoing studies in mouse models, our results underscore the importance of the epigenome as mediator of the effect of external variables and life style factors on distinct cell types, eventually modulating MS disease course.
Presenter Of 1 Presentation
PS08.01 - The Epigenome and Multiple Sclerosis
Abstract
Abstract
Epigenome in Multiple Sclerosis
P. Casaccia1,2; K. Castro1; A. Ntranos3; S. Moyon1; B. Inbar1D.; Marechal1; I. Katz Sand3
1Neuroscience Initiative, CUNY Advanced Science Research Center at The Graduate Center, New York, NY; 2Neuroscience, 3Neurology, Icahn School of Medicine at Mount Sinai, New York, NY
Background: Multiple Sclerosis results from the interaction of genetic predisposition and environmental exposure. Epigenetics refers to the molecular mechanisms by which cells “interpret” external signals, and modulate gene expression. These mechanisms are unique for each cell type and age-dependent. This presentation is focused on DNA methylation.
Objectives: We previously reported differences in the genome-wide distribution of DNA methylation in the normal appearing white matter in post-mortem brains from Multiple Sclerosis patients compared to healthy controls. We generated a mouse model to test the functional relevance of those genes initially identified as hypermethylated in MS brains. In addition, I will review our epigenomic studies conducted in peripheral cells isolated from peripheral blood of RRMS patients.
Methods: DNA methylation was conducted using Illumina bead chip on monocytes from 54 relapsing-remitting therapy-naïve female patients with low or high body mass and in CD4+ lymphocytes, from 47 therapy naive patients, 35 on dimethylfumarate (DMF) and 16 glatiramer acetate (GA) . Functional characterization of novel mouse models generated to test the functional relevance of genes hypermethylated in MS brains will be presented.
Results: DNA methylation in monocytes from RRMS patients differed between high and low BMI groups. Functionally, high BMI correlated with high ceramide levels which induced DNA hypermethylation, affected gene expression and increased the number of circulating monocytes. In patients at the 2 year follow up, the high BMI group showed worsening disability, an effect that could be reproduced in animal models. The study in CD4+ lymphocytes, highlighted the effect of DMF on hypermethylation on the microRNA MIR- 21, which is critical for the differentiation of T helper-17 cells.
Conclusions: External factors, such as disease state, BMI or therapy, affect the behavior of distinct cell types by creating cell-specific DNA methylation patterns in the CNS and in the periphery. These epigenomic changes impact T cell differentiation, modulate the number of circulating monocytes and also affect the ability of oligodendrocyte progenitors to form new myelin after demyelination. Together with additional ongoing studies in mouse models, our results underscore the importance of the epigenome as mediator of the effect of external variables and life style factors on distinct cell types, eventually modulating MS disease course.
Invited Speaker Of 1 Presentation
PS08.01 - The Epigenome and Multiple Sclerosis
Abstract
Abstract
Epigenome in Multiple Sclerosis
P. Casaccia1,2; K. Castro1; A. Ntranos3; S. Moyon1; B. Inbar1D.; Marechal1; I. Katz Sand3
1Neuroscience Initiative, CUNY Advanced Science Research Center at The Graduate Center, New York, NY; 2Neuroscience, 3Neurology, Icahn School of Medicine at Mount Sinai, New York, NY
Background: Multiple Sclerosis results from the interaction of genetic predisposition and environmental exposure. Epigenetics refers to the molecular mechanisms by which cells “interpret” external signals, and modulate gene expression. These mechanisms are unique for each cell type and age-dependent. This presentation is focused on DNA methylation.
Objectives: We previously reported differences in the genome-wide distribution of DNA methylation in the normal appearing white matter in post-mortem brains from Multiple Sclerosis patients compared to healthy controls. We generated a mouse model to test the functional relevance of those genes initially identified as hypermethylated in MS brains. In addition, I will review our epigenomic studies conducted in peripheral cells isolated from peripheral blood of RRMS patients.
Methods: DNA methylation was conducted using Illumina bead chip on monocytes from 54 relapsing-remitting therapy-naïve female patients with low or high body mass and in CD4+ lymphocytes, from 47 therapy naive patients, 35 on dimethylfumarate (DMF) and 16 glatiramer acetate (GA) . Functional characterization of novel mouse models generated to test the functional relevance of genes hypermethylated in MS brains will be presented.
Results: DNA methylation in monocytes from RRMS patients differed between high and low BMI groups. Functionally, high BMI correlated with high ceramide levels which induced DNA hypermethylation, affected gene expression and increased the number of circulating monocytes. In patients at the 2 year follow up, the high BMI group showed worsening disability, an effect that could be reproduced in animal models. The study in CD4+ lymphocytes, highlighted the effect of DMF on hypermethylation on the microRNA MIR- 21, which is critical for the differentiation of T helper-17 cells.
Conclusions: External factors, such as disease state, BMI or therapy, affect the behavior of distinct cell types by creating cell-specific DNA methylation patterns in the CNS and in the periphery. These epigenomic changes impact T cell differentiation, modulate the number of circulating monocytes and also affect the ability of oligodendrocyte progenitors to form new myelin after demyelination. Together with additional ongoing studies in mouse models, our results underscore the importance of the epigenome as mediator of the effect of external variables and life style factors on distinct cell types, eventually modulating MS disease course.