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).