Michael Fedkenheuer, Ph.D., has trained as a research scientist for the past 15 years. His career started with an undergraduate research fellowship in 2008 at James Madison University. Dr. Fedkenheuer worked with the dengue virus envelope protein to study its effects on inflammation in cartilage. Following this, he earned his master's in biochemistry and his doctoral degree in plant pathology at Virginia Tech. Dr. Fedkenheuer published several papers during this time and won awards for his protein structure and flavin biochemistry work. While studying plant pathology, he worked with a team to map resistance genes and breed them into commercial lines.
After obtaining his Ph.D., Dr. Fedkenheuer completed an IRTA traineeship at the NIH/NIAMS in the Lymphocyte Nuclear Biology Group. Using cutting-edge techniques, he studied the role of genome architecture in the DNA repair process. This high-impact work has taken many years and led to the discovery of the mechanism by which loop extrusion impacts classical end joining. Through his research, he gained knowledge and experience and developed valuable, highly engineered cell lines, forming a platform for future studies into DNA damage and genome architecture.
Defects in DNA double-strand break (DSB) repair can lead to outcomes such as cancer, immunological conditions, and developmental defects. The three-dimensional genomic architecture of a cell is known to impact DNA repair, but the mechanism is poorly understood. Our research aims to determine the role loop extrusion plays in DSB repair.
Our research shows that cohesin rings are recruited to DNA breaks, leading to enhanced loop extrusion. We have developed novel cell lines by combining an inducible DNA DSB system with an inducible cohesin depletion system. Our work shows that the complete loss of genome loops leads to multiple DNA repair defects. In the future, we will explore these repair defects relating to cancer and immunology in animal models.