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Research Publications - College of Medicine and Health Science

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Department <strong>of</strong> Biochemistry<br />

10<br />

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Phenomena.<br />

We focused on using complex network analysis<br />

tools to study biological processes such as human<br />

consanguinity <strong>and</strong> congenital disorders,<br />

disease spread in the population using HIV/<br />

AIDS as an example, <strong>and</strong> RNA structure analysis.<br />

These studies have resulted in three MS theses<br />

(two as co-supervisor) <strong>and</strong> one publication.<br />

Sequence comparison <strong>of</strong> MMTV-like fragments amplified out <strong>of</strong> human tissues<br />

compared to MMTV strain Mtv-8 <strong>and</strong> the endogenous human retrovirus HERV-K.<br />

Overall, these sequences revealed over 90% homology with MMTV, but less<br />

than 50% homology with HERV-K. Additionally, the various samples showed<br />

slight differences in their sequence between each other, ruling out any possible<br />

contamination with a laboratory strain <strong>of</strong> MMTV or otherwise.<br />

Mechanisms <strong>of</strong> transcriptional regulation by<br />

chromatin-modifying complexes (Dr. A.H.<br />

Al-Marzouqi)<br />

The research in my laboratory is focused on<br />

underst<strong>and</strong>ing the mechanisms <strong>of</strong> action <strong>of</strong> the<br />

protein complexes that regulate gene expression<br />

by modifying the structure <strong>of</strong> chromatin.<br />

In eukaryotes, the compaction <strong>of</strong> DNA into the<br />

nucleus inhibits the access <strong>of</strong> factors to DNA<br />

which leads to the repression <strong>of</strong> many important<br />

cellular processes required for maintenance<br />

<strong>and</strong> growth <strong>of</strong> the cell. To access the DNA <strong>and</strong><br />

the genes, the nucleoprotein structure, called<br />

chromatin, which consists <strong>of</strong> DNA, histones, <strong>and</strong><br />

non-histone proteins needs to be opened up or<br />

altered. This is accomplished as a result <strong>of</strong> DNA<br />

<strong>and</strong> histone modifications or by DNA binding<br />

proteins. Many studies in the past few years<br />

have described conserved protein complexes<br />

whose function is to modulate the access <strong>of</strong><br />

transcription factors to regulatory regions <strong>of</strong><br />

genes relieving chromatin-mediated repression.<br />

The action <strong>of</strong> these complexes that are able to<br />

overcome the repressive effects <strong>of</strong> chromatin is<br />

an important step in the regulation <strong>of</strong> eukaryotic<br />

gene expression.<br />

Specifically, the overall goals <strong>of</strong> my research<br />

are to underst<strong>and</strong> how certain proteins can<br />

regulate gene expression by modifying the<br />

structure <strong>of</strong> chromatin or interacting with its<br />

components. We are interested in how different<br />

types <strong>of</strong> chromatin modifying proteins work<br />

in turning genes on or <strong>of</strong>f. This is an important<br />

question to be addressed since gene regulation<br />

can determine the amount <strong>of</strong> protein production<br />

required for important functions <strong>of</strong> all cells.<br />

This is also important since many subunits <strong>of</strong><br />

these chromatin-modifying proteins in humans<br />

have been implicated in the initiation <strong>of</strong> various<br />

diseases. It is likely that errors in the function <strong>of</strong><br />

these protein complexes can result in alterations<br />

in the life cycle <strong>of</strong> the cell that may lead<br />

to the development <strong>of</strong> cancer. Thus, we are also<br />

interested in studying how chromatin misregulation<br />

contributes to cancer development <strong>and</strong><br />

could be helpful in finding potential cures for it<br />

in the future.<br />

<strong>Research</strong> highlights<br />

The three areas <strong>of</strong> research focus in my laboratory<br />

during 2011 were:<br />

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the various chromatin-modifying complexes.<br />

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dependent chromatin remodeling complexes.<br />

������������������� in vivo functions <strong>of</strong> chromatin<br />

remodelers <strong>and</strong> their roles in gene silencing<br />

Neuro-modulation <strong>of</strong> the immune response<br />

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My main research interest is to investigate the<br />

mechanism by which organophosphorus compounds<br />

(OPCs) modulate the immune response.<br />

It has been well described that the toxic effects<br />

<strong>of</strong> the OPCs are due to inhibition <strong>of</strong> acetylcholinesterase<br />

(AChE) in the central <strong>and</strong> peripheral<br />

nervous systems, with a consequent increase in<br />

the levels <strong>of</strong> the neurotransmitter acetylcholine<br />

(ACh) which leads to cholinergic hyperstimulation.<br />

We have recently demonstrated that<br />

subchronic doses <strong>of</strong> paraoxon, the bioactive<br />

metabolite <strong>of</strong> the OPC parathion, prepared the

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