Name: Dr. Marek Napierala
Where do you work? My laboratory is located at the University of Alabama at Birmingham, Department of Biochemistry and Molecular Genetics.
How long have you been working on FA and who was the first fellow FA researcher you met? I have been working on repeat expansion diseases for the past ~ 25 years and focusing on FA for the past 18 years. The first researcher I met in the field was Dr. Robert D. Wells, who then was heading the Center of Genome Research Institute of Biosciences and Technology Texas A&M University in Houston. He was working on various repeat sequences, including GAA repeats. At the time (1995), we did not know that these repeats are expanded in the FXN gene in people with FA.
What got you interested in FA research? I was interested in repetitive DNA elements even prior to the discovery that expanded GAA repeats are the mutation causing FA. The mechanism of how unstable repeat sequences expand from a few repeats to hundreds and even thousands intrigued me when I was a graduate student and during my early career as a postdoc. Then, this interest evolved into a fascination with understanding the connection between expanded DNA and decreased frataxin expression (i.e. mechanism of epigenetic silencing). This was certainly influenced by a collaboration between my mentor at the time (Dr. Wells) and Dr. Joel Gottesfeld (Scrippts Institute), whose group discovered and defined epigenetic changes at the FXN gene.
What question or challenge were you setting out to address when you started this work? When I started as a postdoc working on FA, we did not know the mechanism causing the transcriptional block in FA. We knew that the atypical DNA shape adopted by long GAA repeats was a part of it, but we also suspected that this was not the only reason. We were, and still are, puzzled by the unusual properties of these repetitive DNA sequences that enable them to grow (i.e. increase number of repeats).
What research topics or questions are you currently focused on? My lab works on several aspects of FA, with three major groups of projects. The first addresses the basic biology underlying FA, focusing on mechanisms causing GAA repeat expansions, how these repeats lead to reduced levels of frataxin and how to shorten them. A second part of my group works on translational projects related to potential therapeutic approaches for FA. These approaches are tested in patient cells that we hold in a repository and in animal models of the disease. The third line of research in my laboratory is related to a subgroup of FA caused by a combination of a GAA repeat expansion and a point mutation affecting the frataxin gene.
What do you hope to achieve or what excites you in FA research? The mission of our laboratory is to contribute to the development of therapies and a cure for Friedreich’s Ataxia by elucidating molecular mechanisms causing the disease, developing novel cellular and animal models of FA, identifying disease, biomarkers and testing novel therapeutic approaches.
If you have met someone living with FA, please tell us about that interaction. Did it have an impact on your work? Personally, I have met many people with FA, some of whom I consider my friends. The first person I met was Kyle Bryant on his first rideATAXIA when I was working in Houston. Shortly after establishing my laboratory at UAB, I initiated interactive symposia in which small groups of FA patients and their families are invited to spend a day in our laboratory at UAB. These visits allow our guests to become familiar with current FA research being conducted by our group through short talks presented by my lab members in lay terms followed by an open question/answer period and round-table conversation. A highlight of the day is a tour of the laboratory where they can see for themselves how we visualize molecular features of the disease (e.g. GAA repeat size), they can view different cell culture models being used in our research and for testing potential drug candidates. These symposia also allow the members of my laboratory to realize the impact FA has on peoples’ lives. This gives all people in my group additional motivation to work even harder to answer our research questions.
You serve voluntarily on FARA's Scientific Advisory Board. Please tell us what you see as FARA's key role in the research process. This is a difficult question to answer as FARA plays instrumental roles in many aspects of our fight to find a cure for FA. From a research perspective, I think the most important role of FARA is connecting people – connecting scientists with other scientists, connecting research groups, connecting pharma/biotech with academia and facilitating interactions, exchanges of information and ideas between all researchers. This is a critical role allowing research to move at a significantly faster pace.
Tell us more about yourself and/ or your journey with FA research. As our laboratory continues to change and grow, our focus on FA research remains constant. This journey towards a cure for FA would not be possible without the support and commitment of Dr. Jill Napierala, my wife and partner in running our laboratory. Together, we oversee all aspects of our research program and will continue our dedicated approach to finding a cure for FA.