Trainee Author: Lise Barbé, PhD
(Photo courtesy Dr. Barbé)
This paper was selected for the Trainee Paper Spotlight because it sheds light into the genetic mechanisms underlying myotonic dystrophy. This disease is caused by tri-nucleotide repeat expansions in the gene DMPK, which incompletely explain the large variation in disease severity observed in patients. The authors demonstrate that hypermethylation upstream of the maternally inherited allele correlates with a severe version of the disease, congenital myotonic dystrophy. Additionally, upstream methylation status predicts disease severity more accurately than repeat length alone. This study not only establishes a potential cellular mechanism responsible for disease, but also proposes a valuable prenatal diagnostic tool.
Training & Development Committee: Could you describe your research for us?
Dr. Barbé: The molecular mechanisms responsible for the onset and severity of repeat diseases, such as myotonic dystrophy and Huntington’s disease, are largely unknown. This paper shows that methylation rather than repeat size dictates disease severity in patients with myotonic dystrophy. However, we do not understand the exact mechanisms underlying this effect. During my postdoctoral training, I will unravel the mechanisms behind the methylation-driven onset and severity using cutting-edge techniques, such as robotic microscopy. While current research in the field of Huntington’s disease focuses mainly on HTT protein dysregulation, this mechanism cannot solve all disease-related questions. In my work, I will characterize how epigenetics and mutant RNA affect disease development and manifestation.
TDC: What are your career goals?
Dr. Barbé: I love to be on the verge of translational research and to discover disease mechanisms that may lead to new therapeutic targets. My long-term career goal is to lead a successful independent academic lab studying how epigenetic regulation contributes to normal biology and disease pathology, particularly in repeat diseases.
TDC: Why did you choose genetics as your field of study?
Dr. Barbé: Since a young age, I have been interested in science and understanding how nature works. During high school and my undergraduate studies, I was fascinated by genetic diseases, so I pursued a master’s degree in reproduction and genetics in Brussels, Belgium. During my graduate studies, I became interested in repeat diseases and the complex biology that determines their symptoms. I am still fascinated by how a repetitive DNA sequence can dysregulate the cell in so many different ways. This fascination drives my research.
TDC: Describe yourself in three words.
Dr. Barbé: Curious, Adventurous, Independent
The Trainee Paper Spotlight is a quarterly feature highlighting outstanding papers written by trainee members of ASHG.