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Featured Scientist - 2016-2017

FDr Matt Hierschey Dr. Matt Hirschey

By Eileen O’Connor

Matt Hirschey’s favorite grade school class involved what he de- scribes as “crazy logic puzzles” in which you try to problem solve and restore the order of things. For as long as he can remember he has been drawn to the challenge of problem solving – and to- day it is this passion to answer some of the most challenging ques- tions in the field of Molecular Physiology that motivates Hirschey in his work at Duke University Medical Center, where he is lead- ing a team in FA research.

Dr. Hirschey, an Associate Professor in the Departments of Medi- cine and Pharmacology, traces his interest in physiology and drive to understand how the body works to his background as a com- petitive athlete. A lifelong runner and track and field competi- tor at the University of Vermont, he has always been fascinated by how the body metabolizes and produces energy. Originally Hirschey intended to pursue a medical degree, but his passion for research and problem solving led him to earn a PhD in chemis- try, which he received from the University of California in Santa Barbara.

As an athlete and father of two young children, Hirschey has an intimate understanding and appreciation for how a body func- tions in optimal health – and what it can and must be like to feel and to see a healthy body begin to fail. Over the past few years Hirschey has had the opportunity to meet patients and families living with FA and describes how these interactions help to keep him focused. “As a father it’s tough to meet and to see these par- ents – to know how hard it must be. Hard doesn’t even come close,” he quickly added.

Last year Hirschey and some of his colleagues attended the FA international meeting in Windsor, England and this past summer met FARA staff and FA ambassadors at an event in North Caro- lina. “I think it (these interactions) matters. We are in the lab tin- kering away with models and biochemical reactions and it’s hard because science is slow. We try to be rigorous and meeting actual patients helps us to stay motivated.”

In his five years at Duke, Hirschey has become a leading research- er on the process of acetylation of proteins in mitochondria, which fortuitously for the FA community, led to a partnership with cardiologist and FA researcher, Dr. Mark Payne. Four years ago Hirschey came across a paper detailing Payne’s research and findings about an FA mouse model that was accumulating these tags or markers on cardiac proteins at a higher rate than normal. This did not make sense to Hirschey and his colleagues.

“With FA we found an interesting problem – which was scream- ing ‘we don’t understand how this works!’” said Hirschey. As the FA ‘puzzle’ presented itself, Hirschey, immediately was hooked. Hirschey and Payne wrote a grant to FARA to study the process of acetylation in mitochondria as it relates to heart disease. Their work has shown promising results. Given this writer’s very lim- ited scientific sensibilities, Hirschey tried to explain their findings in as simple a language possible:

“The markers are controlled by a protein called Sirtuin. There are seven different Sirtuin proteins in different parts of the cell that perform the same type of enzymatic activity. In FA patients at least one of the Sirtuins is inactive. The way to activate Sirtuin is to give a boost. A boost that has been identified as effective in this way is called NAD. NAD (an acronym for nicotinamide ad- enine dinucleotide) is like a vitamin. When you give the vitamin, you boost NAD and can shift metabolism and make disease states better. When FA mouse models are given a NAD precursor, early data show the amelioration of cardiac conditions, and it appears to offset cardiac problems that the mouse develops.”

Simply put: “There is emerging data showing the positive effects of NAD therapy in FA.”

When asked what he is most excited by in his current FA research, Hirschey immediately identifies these findings: “That the pre- clinical trials on NAD supplements show that a decline in heart function slows – and the fact that these findings could impact sev- eral other diseases – diabetes, obesity, heart failure and the effects of aging. Hirschey also notes that a paper published recently in Cell Metabolism that shows another ataxia (Ataxia Telangiecta- sia, A-T) significantly improved with NAD supplement therapy (https://www.ncbi.nlm.nih.gov/pubmed/27732836).

While the intricacies of scientific research may not always resonate with everyone, this writer is convinced that with the imagination and passion of a scientist like Hirschey, tremendous strides and breakthroughs are not only possible – but very probable indeed.

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