Alharfoush, Enmar: Epigenetic of Adenosine

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Title: Epigenetic of Adenosine

Name: Enmar Alharfoush

Major: Cell Biology and Neuroscience

School affiliation: School of Arts and Sciences

Programs: Aresty – Research or Conference Funding Recipient

Other contributors: Detlev Boison

Abstract: Epigenetics is an emerging research area. Recent studies have shown that pathological changes to histone modifications are implicated in the progression and development of pathological conditions such as cancer and epilepsy. It has been previously shown that adenosine kinase (ADK) can act as an epigenetic regulator that biochemically affects the DNA methylation pathway by effectively removing adenosine. I hypothesize that, in addition to DNA methylation, ADK also regulates histone methylation, a new potential role of ADK which has not yet been studied. The goal of this study was to test a mechanistic relationship between ADK and histone methylation by using engineered cell lines expressing different isoforms of ADK at different levels as well as pharmacological inhibition of ADK.
The expression of ADK isoforms in different genetically engineered cell lines was assessed and an experimental paradigm using pharmacological intervention with the ADK inhibitor 5-iodotuburicidin was optimized. DNA and histone methylation status were quantified under those conditions. Preliminary experiments show that pharmacological inhibition of ADK can modify histone methylation patterns.
The outcome of this study is the initial characterization of a novel epigenetic mechanism for the regulation of histone methylation. This could potentially lead to the development of treatments for several conditions in which pathological histone modifications are involved.