A5102866352- Soybean genetics and cultivation
- Epigenetics and DNA Methylation
- Genetics, Aging, and Longevity in Model Organisms
- Genetics and Neurodevelopmental Disorders
- Plant Molecular Biology Research
- Plant nutrient uptake and metabolism
- Sirtuins and Resveratrol in Medicine
- Birth, Development, and Health
- Circadian rhythm and melatonin
- Nutrition, Genetics, and Disease
- Genomics and Chromatin Dynamics
- Biochemical effects in animals
- Genetic Mapping and Diversity in Plants and Animals
- Health and Well-being Studies
- Legume Nitrogen Fixing Symbiosis
- Neuroethics, Human Enhancement, Biomedical Innovations
- Biochemical and Molecular Research
- Retinoids in leukemia and cellular processes
- Immunotherapy and Immune Responses
- Pluripotent Stem Cells Research
- Evolution and Genetic Dynamics
- Photosynthetic Processes and Mechanisms
- ATP Synthase and ATPases Research
- CAR-T cell therapy research
- Wheat and Barley Genetics and Pathology
Harvard University
2018-2024
Boston VA Research Institute
2019-2024
Scripps Research Institute
2012-2022
New York University
2019
University of Georgia
2016-2018
Harvard University Press
2018
A hallmark of eukaryotic aging is a loss epigenetic information, process that can be reversed. We have previously shown the ectopic induction Yamanaka factors OCT4, SOX2, and KLF4 (OSK) in mammals restore youthful DNA methylation patterns, transcript profiles, tissue function, without erasing cellular identity, requires active demethylation. To screen for molecules reverse rejuvenate human cells altering genome, we developed high-throughput cell-based assays distinguish young from old...
The evolution of gene body methylation (gbM), its origins, and functional consequences are poorly understood. By pairing the largest collection transcriptomes (>1000) methylomes (77) across Viridiplantae, we provide novel insights into gbM relationship to CHROMOMETHYLASE (CMT) proteins.CMTs evolutionary conserved DNA methyltransferases in Viridiplantae. Duplication events gave rise what now referred as CMT1, 2 3. Independent losses 2, 3 eudicots, CMT2 ZMET monocots monocots/commelinids,...
The nonmethylable cytosine analogs, 5-azacytidine and zebularine, are widely used to inhibit DNA methyltransferase activity reduce genomic methylation. In this study, whole-genome bisulfite sequencing is construct maps of methylation with single base pair resolution in Arabidopsis thaliana seedlings treated each demethylating agent. We find that both inhibitor treatments result nearly indistinguishable patterns genome-wide had a slightly greater effect at higher concentrations across the...
To gain insight into how researchers of aging perceive the process they study, we conducted a survey among experts in field. While highlighting some common features aging, exposed broad disagreement on foundational issues. What is aging? causes it? When does it begin? constitutes rejuvenation? Not only was there no consensus these and other core questions, but none questions received majority opinion-even regarding need for itself. Despite many believing understand their understanding...
SUMMARY Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family defensive deacylases. During aging, levels NAD + can decrease by up to 50% some tissues, repletion which provides range health benefits both mice humans. Whether or not precursor nicotinamide mononucleotide (NMN) extends lifespan mammals known. Here we investigate effect long-term administration NMN on...
Abstract The number of rachis nodes (spikelets) on a wheat spike is component grain yield that correlates with flowering time. genetic basis regulating in cereals well understood, but there are reports time can be modified at high frequency by selective breeding, suggesting it may regulated both epigenetic and mechanisms. We investigated the role DNA methylation spikelet treating semi‐spring demethylating agent, Zebularine. Three lines heritable increase were identified. molecular for...
SUMMARY All living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. As budding yeast cells age, changes result in cell identity sterility, both hallmarks aging. In mammals, is also lost time, but what causes it to be whether cause or consequence aging not known. Here we show that the transient induction genomic instability, form low number non-mutagenic DNA breaks, accelerates many chromatin tissue seen during aging, including erosion...
SUMMARY There are numerous hallmarks of aging in mammals, but no unifying cause has been identified. In budding yeast, is associated with a loss epigenetic information that occurs response to genome instability, particularly DNA double-strand breaks (DSBs). Mammals also undergo predictable changes age, including alterations methylation patterns serve as “age” clocks, what drives these not known. Using transgenic mouse system called “ICE” (for inducible c hanges the e pigenome), we show...
All living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. As budding yeast cells age, changes result in cell identity sterility, both hallmarks aging. In mammals, is also lost time, but what causes it to be whether cause or consequence aging not known. Here we show that the transient induction genomic instability, form low number non-mutagenic DNA breaks, accelerates many chromatin tissue seen during aging, including erosion...
ABSTRACT Background The evolution of gene body methylation (gbM), its origins and functional consequences are poorly understood. By pairing the largest collection transcriptomes (>1000) methylomes (77) across Viridiplantae we provide novel insights into gbM relationship to CHROMOMETHYLASE (CMT) proteins. Results CMTs evolutionary conserved DNA methyltransferases in Viridiplantae. Duplication events gave rise what now referred as CMT1, 2 3. Independent losses 3 eudicots, CMT2 ZMET monocots...
Abstract Epigenetic “clocks” based on DNA methylation (DNAme) have emerged as the most robust and widely employed aging biomarkers, but conventional methods for applying them are expensive laborious. Here, we develop T agmentation-based Indexing M ethylation Seq uencing (TIME-Seq), a highly multiplexed scalable method low-cost epigenetic clocks. Using TIME-Seq, applied multi-tissue tissue-specific clocks to over 1,600 mouse samples. We also discovered novel approach age prediction from...
There are numerous hallmarks of aging in mammals, but no unifying cause has been identified. In budding yeast, is associated with a loss epigenetic information that occurs response to genome instability, particularly DNA double-strand breaks (DSBs). Mammals also undergo predictable changes age, including alterations methylation patterns serve as "age" clocks, what drives these not known. Using transgenic mouse system called "ICE" (for inducible the epigenome), we show tissue's non-mutagenic...
Abstract Cancer cells, aging and cells from patients with the developmental disorder Immunodeficiency, C entromeric instability, F acial anomalies (ICF) syndrome frequently display a striking loss of DNA methylation (hypomethylation) that is accompanied by increased damage chromosomal rearrangements. Despite robust link, mechanism which hypomethylation leads to genomic instability poorly understood. We report human pericentromeric repeat sequence Satellite 2 (SAT2) poses challenges...
Abstract We have shown that members of the non-muscle myosin II (NMII) family molecular motors are non-redundant drivers both invasion and proliferation in glioblastoma (GBM), consistent with canonical roles NMII isoforms play cell motility cytokinesis. However, we also found has a non-canonical role by regulating oncogenic signaling pathways relevant to GBM pathogenesis. This unexpected finding led us identify characterize MT-125, highly specific small molecule inhibitor two predominant...
All living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. In yeast, changes result in cell identity sterility, both hallmarks yeast aging. mammals, is also lost time, but what causes it to be whether cause or consequence aging not known. Using transgenic mouse system called "ICE" (for Inducible Changes the Epigenome), we show that process repairing non-mutagenic DNA breaks accelerates age-related physiological, cognitive, molecular...
Abstract The non-methylable cytosine analogs, 5-azacytidine and zebularine, are widely used to inhibit DNA methyltransferase activity reduce genomic methylation. In this study, whole-genome bisulfite sequencing is construct maps of methylation with single base pair resolution in Arabidopsis thaliana seedlings treated each demethylating agent. We find that both inhibitor treatments result nearly indistinguishable patterns genome-wide had a slightly greater effect across the genome at higher...
Epigenetic “clocks” based on DNA methylation (DNAme) are the most robust and widely-used aging biomarkers, but prevailing clock methods expensive laborious. Here, we describe Tagmentation-based Indexing for Methylation Sequencing (TIME-Seq), a highly-scalable approach low-cost epigenetic clocks. With TIME-Seq, predict age in 3,556 human mouse samples from nine tissue- cell-types. We show that TIME-Seq clocks accurate robust, enriched Polycomb Repressive Complex 2 (PRC2)-regulated loci,...
Abstract The nuclear receptor RORγ has been shown to play an essential role in the development of Th17 cells. Previously, it was reported that potent and selective inverse agonist SR2211 effective at modulating activity cell culture. More recently we demonstrated can repress expression production inflammatory cytokines cells LPS stimulated RAW264.7 Here present vivo efficacy experimental model arthritis, murine collagen induced arthritis or CIA model. Significantly reduced Joint scores were...