School of Medicine

Wayne State University School of Medicine

Dr. Krawetz team cracks secret of genome, nuclear matrix interaction

Stephen A. Krawetz, Ph.D.

Stephen A. Krawetz, Ph.D.

A team of Wayne State University School of Medicine researchers has unraveled the secret of interactions between the human genome and the nuclear matrix, a finding that could lead to genetic treatments for myriad diseases and disorders. The findings were published in and featured on the cover of the journal Human Molecular Genetics.

The authors of the findings are Stephen A. Krawetz, Ph.D., the Charlotte B. Failing professor of Fetal Therapy and Diagnosis; director of Translational Reproductive Systems, Department of Obstetrics and Gynecology, Center for Molecular Medicine and Genetics, and the Institute for Scientific Computing; Amelia Linnemann, Ph.D., of the Center for Molecular Medicine and Genetics; and Adrian Platts, of the Department of Obstetrics and Gynecology and the Center for Molecular Medicine and Genetics.

Dr. Krawetz’s laboratory tries to understand how the genome is organized in the three-dimensional space of the nucleus to orchestrate gene activity. Using rapid large scale genomic techniques, the researchers defined key context dependent interactions of genes with specific regions of the nuclear matrix organizer. The interaction between the two played a role in gene expression. The finding may lead to methods that switch on or switch off genes that are at the root of diseases or disorders.

The research and resulting published paper formed the cornerstone of Ms. Linnemann’s doctoral thesis. Mr. Platts is the lab’s primary biosystems informatician. Initially trained as a physicist, he is “naturally quite at home developing novel analytical tools suited to this voluminous data and the statistical rigors that are required for these large scale projects,” Dr. Krawetz said.

“The contribution of these individuals highlight the breadth, yet focused nature of my research program, which, since its inception, has been dedicated to using Systems Approaches to develop self-help therapeutics,” Dr. Krawetz explained. “My laboratory strives to realize bench-to-beside personalized medicine at Wayne State University.

“For some time now the majority of the human genetic code has been known,” Dr. Krawetz said. “But how this information is used by the body -- to choose which genes within the cell to activate or leave dormant -- still remains largely unknown. In this recent work we have shown that structures within the cell's nucleus partner with the DNA in the functional regulation of the genome.”

Understanding how DNA is switched between active and dormant states, he explained, “opens a new door to the mechanism by which cells acquire their distinct specializations.” The knowledge provides the structural “mechanistic link to genome reprogramming,” essential in a healthy child and life.

“This opens up new possibilities for indirect (epigenetic) treatment therapies for diseases, including, dystrophies, premature aging, several types of cancers and reproductive fitness,” Dr. Krawetz said.

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