Posted by Amanda Rickard on Apr 15, 2018
Dr. Anna Pakula studies FSHD and Duchenne’s Muscular Dystrophy as a postdoctoral researcher in Dr. Louis Kunkel’s lab at Boston Children’s Hospital. Her grant, titled “Understanding the Initiation and Progression of FSHD-1 Disease by use of Single Cell Transcriptomics,” was recently funded by Friends of FSH Research. We interviewed Dr. Pakula to learn more about her work and its implications for the development of an FSHD treatment.
What made you decide to study FSHD during your postdoctoral fellowship?
As a molecular biologist I was always interested in human anatomy, in particular muscle structure and physiology. Muscles constitute around 40% of the human body and without them body locomotion would be impossible. FSHD, which I learned about during my PhD, is the most prevalent muscular dystrophy and is complex and heterogeneous (Note: “heterogeneous” means that the disorder varies a lot from patient to patient) . Unfortunately, there is no cure for FSHD1 or FSHD2. Since so many FSHD patients suffer from the disease, I think there is an urgent need for finding a treatment.
Why is it important to measure the RNA of FSHD muscle cells?
Measurement of RNA from FSHD cells gives us information about what exactly is happening inside cells before other events like translation occur (RNA gets translated into protein). This means we will be able to trace the early steps of disease initiation by looking at RNA level. In these studies we are interested in looking at DUX4 RNA levels by using a technology called single cell transcriptomics. We will also follow what happens later on, on the protein level by performing DUX4 immunostaining (Note: researchers can use specific antibody probes connected to dyes in order to stain and visualize proteins, called “immunostaining”).
How can single cell RNA analysis be especially helpful for understanding FSHD, compared to previously published studies of FSHD RNA?
This single cell analysis will help us in classifying primary muscle cells in particular into subgroups of cells expressing DUX4 (double homeobox 4) - a well known disease player. Information coming from these particular cells may help us to understand the initiation of the disease whereas analyzing non-DUX4 cells will give us an idea about the disease progression.
Previous RNA studies were performed on pooled groups of FSHD cells, whereas in this project we will analyze cells one by one.
How do you think that your research will contribute to our quest for a treatment for FSHD?
I believe that grouping FSHD cells and comparing them to non-FSHD cells will give us insights into molecular pathways involved in disease initiation and progression. These studies will help us to select molecular pathways that should be considered for further research. We hope that selecting them and then targeting them using drugs (in mice) will lead to identification of targeted treatments.