Shinozaki receives $3.1 million grant for study on epigenetics of psychiatric disorders

Gen Shinozaki, MD, University of Iowa associate professor of psychiatry and neurosurgery, was awarded a five-year, $3.1 million grant from the National Institute of Mental Health (NIMH) to study the correlation of epigenetic marks between human brain tissue and peripheral tissues.

Recent advances in molecular genetics have shown the advantages of using epigenetics to provide valuable information about the underlying brain biology of psychiatric disorders.

Shinozaki’s lab focuses on epigenetic mechanisms, specifically DNA methylation, to study conditions such as post-traumatic stress disorder (PTSD), depression, and delirium. While genetic information is static, epigenetic factors are influenced by stressors, trauma, infection, or inflammation and may provide more dynamic information about psychiatric diseases that change or develop in response to environmental factors.

“The pathophysiology of mental illness resides in the brain, and unfortunately in most cases, there is no access to brain tissue in a living human being,” Shinozaki said. “So, we largely rely on peripheral tissues to examine epigenetic status.”

Peripheral tissues, such as blood or saliva, are used most often to assess epigenetics, but this poses a challenge for interpreting data because epigenetic status varies depending on the tissue type. It is not known how accurately DNA methylation changes in blood and saliva reflect changes in the brain.

For scientists to continue using peripheral tissues as a surrogate for what is happening in the brain, it is important to compare the epigenetic marks in both tissue types, Shinozaki says.  

Through collaborations with colleagues in the Departments of Neurosurgery and Pathology, Shinozaki’s lab will conduct a genome-wide DNA methylation analysis using live human brain tissue samples. These samples will be collected during neurosurgery procedures and pathological autopsies. Blood, saliva, and buccal (cheek swab) samples will be collected at the same time, in order to compare the two sources of epigenetic information.

Shinozaki plans to develop a database that will allow other researchers to identify genomic regions where epigenetic marks are highly correlated between both tissue types, or to select the best surrogate tissue for their genes of interest.

Shinozaki is the principal investigator on the grant. Other members of the UI team include Marco Hefti, MD, in the Department of Pathology, as well as Hiroto Kawasaki, MD, and Matt Howard, MD, in the Department of Neurosurgery.