BBI Faculty Conversations: Dr. Lisa Maves

Dr. Maves is an Associate Professor in the Center for Developmental and Regenerative Medicine at Seattle Children’s Research Institute (SCRI)


Dr. Lisa Maves Dr. Lisa Maves: The ultimate goal would be to have our work inform a therapy that could help delay or in some way slow the devastating progressive muscle degeneration before the damage is done.

BBI: Can you tell us about your journey to science and your eventual research focus?

Dr. Maves: Starting way back, my dad was a veterinarian and had a microscope in his clinic. I became obsessed with looking at anything I could under that microscope. By the time I got to college, I got involved in doing undergraduate lab research. I remember realizing how much I enjoyed the independence of lab work, and that I especially enjoyed developmental biology.

I did my graduate work in drosophila (or fruit flies) and loved the way we could manipulate turning on and off genes using techniques that at the time were quite new. For my post-doctoral work, I switched to zebrafish because of the ability to watch embryogenesis under the microscope. I was lucky to start my lab around the time CRISPR methods were becoming available. Now with CRISPR, we have the tools to design essentially any gene manipulation we want in zebrafish, and this is the main model we use in my lab.

BBI: What has your work focused on in Zebrafish since then?

Dr. Maves: When I started my lab here at Children’s, I wanted our work to start taking a disease-model focus. Two of our main projects are using Zebrafish as a model for Duchenne Muscular Dystrophy (DMD) and as a model for studying congenital heart defects. In our work on DMD, we are using the Zebrafish to understand the developmental biology of that disease, including its earliest phenotypes and effects. Muscular Dystrophy is caused by a loss of the gene dystrophin that helps keep muscle cells intact. Duchenne’s impacts young boys and causes what is usually devastating and progressive muscle loss of function. We are beginning to see evidence that very early treatment can aid in ameliorating the progressive deterioration that happens later. We are trying to use Zebrafish, as well as collaboration with Dr. David Mack’s lab at the Institute for Stem Cell and Regenerative Medicine, to use multiple Duchenne disease models to understand the very earliest phenotypic manifestations of DMD.

BBI: How has your work intersected with BBI?

Dr. Maves: Dr. Mack and I had been working on a grant proposal related to this work to the NIH. We received a BBI Catalytic Collaborations Grant in 2019 to help get the collaboration going and get some preliminary data. That BBI grant really helped propel our collaboration forward and, I believe, helped make possible the R01 NIH grant we have now.

BBI: Congratulations! How has this research progressed since then?

Dr. Maves: We now have some single cell RNA sequencing in the Zebrafish model as well as in Dr. Mack’s human cell models. We are hoping to use that to help us understand the earliest effects of the disease. The hope is we can compare the data between our two disease models and understand the earliest conserved effects of DMD at a cellular level. We believe this will give us some clues to what might be some of the earliest beneficial targets for therapies in this terrible disease. There is a long way to go, but the ultimate goal would be to have our work inform a therapy that could help delay or in some way slow the devastating progressive muscle degeneration before the damage is done.

BBI: On that note, where do you think this work goes next?

Dr. Maves: I’d like to think that our work will help guide some of the therapies that are in progress for the disorder, in particular CRISPR gene therapies that are being explored. Our data could one day help guide how and when those therapies are deployed in affected individuals. Right now, this disease is generally diagnosed at approximately age 3 to 4 years in boys when they begin to show symptoms. This work could support even earlier genetic testing and identification of affected boys with the disorder for possible treatment before they begin to show symptoms.

BBI: Thank you for taking the time to speak with us today and congratulations again!