Research
We study how early and late experience-driven brain activity shapes the epigenome and the 3D- chromatin architecture, in both healthy and diseased states.
The environment can have a long-lasting effect on the organisms’ biology, physiology and behavior. While some environmental conditions can be beneficial, others can result in maladaptive responses and lead to pathologies. Over the years, many studies have shown that gene expression programs can be predisposed by environmentally induced epigenetic changes that may alter the phenotypes of the organism.
Our lab examines how different environmental stimuli shapes the brain epigenome and regulates 3D- chromatin organization. We are interested to understand how this process leads to long-lasting changes in gene expression, neuronal activity, physiology, and behavior. A secondary goal is to understand whether epigenetic programming in the early stages of development can affect the behavioral-physiological phenotype of the adult organism and how these changes can pass onto future generations.
Delineate the principals of activity-dependent spatial genomic organization in the brain.
Non-coding regulatory elements (ncREs) are short regions of DNA that bind transcription factors (TFs) to either promote or repress transcription of distal genes. Although these regions comprise a large percent of all mammalian genome, our knowledge of these elements remain surprisingly incomplete.
A functional hallmark of regulatory elements is that they act independent of the distance or orientation to their target genes, and can bypass thousands of
base pairs of the linear genome by forming three dimensional (3D) DNA loops, thus posing a challenge to map these elements to their respective genes. New approaches such as chromosome conformation capture (3C) techniques, allow us to map 3D -chromatin contacts on a genome-wide scale and elucidate the exact targets of ncREs.
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We are particularly interested to map and decipher the role of these regulatory elements in major brain function and in a cell type specific resolution. Furthermore, we aim to understand how regulatory elements interact with TFs and other epigenetic modifications to control and promote important transcriptional programs, in both healthy and diseased states.
Uncovering the genome-wide effects of intermittent fasting on chromatin modulation and transcriptional programs to improve brain health and cognitive performance
Intermittent fasting (IF) regimens possess various brain’ health benefits. Despite IF being criticized as a fad, accumulating evidence shows that this dietary regimen increases physical performances, decrease oxidative stress, attenuate inflammation and reduce risk factors for various neurological disorders. However, rigid fasting regimes are notoriously difficult to sustain for prolonged periods of time, therefore it is vital to understand whether these alterations also trigger stable adaptive molecular modifications that will carry over, long–after the fasting period is over. Furthermore, to what extent these beneficial effect is contributed by chromatin modulation, needs further investigation.
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Our main goal is to uncover the epigenetic mechanisms that mediate the brain’ health benefits of IF and test whether these effects are stable and last over long periods of time (even after the fasting period. We specifically interested in understanding the close interaction between the main ‘fuel’ product of IF –ketone bodies, chromatin conformation and genomic stability.