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Michael Trimarchi, PhD Candidate

Award Name TL1

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Changes in the DNA methylome and endometrial cancer

The Wexner Medical Center at The Ohio State University’s Center for Clinical and Translational Science has awarded a TL1 Award to Michael Trimarchi, PhD Candidate, for his research on ‘Changes in the DNA methylome and their impact on tumor recurrence in endometrial cancer using next-generation sequencing.’

“In the past, investigators typically assessed the DNA gene by gene or one chromosomal position at a time,” said Trimarchi. “The novelty of our approach is that we are assessing the whole genome at the same time, without cherry-picking our favorite loci, by taking advantage of the advances in next-generation sequencing.”

Trimarchi started out as a bench scientist. To analyze the project’s large datasets, he taught himself basic computer programming and statistics with the help of group members and his computational mentor. He also interacts frequently with his mentorship team, including an expert in methylation sequencing, a biologist, and a clinician. He hopes the bioinformatic techniques he learns from this project, combined with his experience as a bench scientist, will aid him in future multidisciplinary research.

DNA methylation is an important modification that can control gene expression and is believed to affect cell differentiation and organism development. In biology, protein structure determines function. This concept may also be applicable to DNA. Modifications made to DNA may cause the DNA to be arranged differently in the cell, affecting which genes (and therefore, proteins) are expressed.

“My core purpose for this research is to find biomarkers that correlate with tumor recurrence in endometrial cancer patients,” said Trimarchi. “If I could identify signaling pathways impacted by methylation that might be a target for therapeutics, that would be great as well—but our study design is better suited to find correlation rather than causation.”

To perform their analysis, Trimarchi and his colleagues extract the DNA from patient tumors, enrich for methylated DNA fragments and sequence them. Next, they match the methylated fragments to their positions in the genome, adjust for technical biases and count the fragments to compute the “methylation signal” across the genome. They compare the methylation signal between patient samples to find genomic regions that are methylated in some patients but not in others.

A portion of Trimarchi’s research has recently been accepted for presentation at the International Conference on Intelligent Biology and Medicine in Nashville, Tennessee and is in review for publication in a Biomedical Central journal later this year.

Trimarchi has high hopes for his research, which could eventually lead to a panel of biomarkers that could be used to identify patients with poor outcomes so they can be more aggressively treated.

“I’m hoping that my research will help improve the stratification and the treatment of patients with endometrial cancer,” Trimarchi said. “Perhaps some of the themes I identify will be helpful in other cancers as well.”

By Lauren Sheridan, Thursday, July 5, 2012

Related Pages

Awardee Profiles
Mentored Research Training Program (TL1)
Acknowledging CTSA grant support in publications

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