Summary

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.

Research Statement

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. 

Scientific Publications

Characterization and clustering of kinase isoform expression in metastatic melanoma.

Holland DO, Gotea V, Fedkenheuer K, Jaiswal SK, Baugher C, Tan H, Fedkenheuer M, Elnitski L
PLoS Comput Biol.
2022 May;
18(5).
doi: 10.1371/journal.pcbi.1010065
PMID: 35560144

Arg279 is the key regulator of coenzyme selectivity in the flavin-dependent ornithine monooxygenase SidA.

Robinson R, Franceschini S, Fedkenheuer M, Rodriguez PJ, Ellerbrock J, Romero E, Echandi MP, Martin Del Campo JS, Sobrado P
Biochim Biophys Acta.
2014 Apr;
1844(4).
doi: 10.1016/j.bbapap.2014.02.005
PMID: 24534646

Structural insight into the mechanism of oxygen activation and substrate selectivity of flavin-dependent N-hydroxylating monooxygenases.

Franceschini S, Fedkenheuer M, Vogelaar NJ, Robinson HH, Sobrado P, Mattevi A
Biochemistry.
2012 Sep 11;
51(36).

Dual role of NADP(H) in the reaction of a flavin dependent N-hydroxylating monooxygenase.

Romero E, Fedkenheuer M, Chocklett SW, Qi J, Oppenheimer M, Sobrado P
Biochim Biophys Acta.
2012 Jun;
1824(6).
doi: 10.1016/j.bbapap.2012.03.004
PMID: 22465572

Education

Virginia Tech
Ph.D., Plant Pathology (2016)

Virginia Tech
M.S., Biochemistry (2012)

James Madison University
B.S., Biotechnology (2010)

Experience

Research Fellow
NIH/NIAMS (2023-present)

IRTA Postdoctoral Fellow
NIH/NIAMS (2018-2022)

Laboratory and Research Specialist
Virginia Tech (2016-2018)

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