My lab focuses on channelopathies – inherited diseases linked to mutations in ion channels. We’re most interested in mutations in two voltage-gated Na+ channel genes, SCN1A and SCN1B, that cause pediatric epilepsies like Dravet syndrome, a severe epileptic encephalopathy that includes developmental delay and mental retardation. These children also have a high risk of Sudden Unexplained Death in Epilepsy (SUDEP) that may be caused by cardiac arrhythmia.
I am fascinated by the idea that combined defects in cell-cell adhesion and cellular excitability resulting from mutations in Na+ channel genes may lead to abnormal brain and heart development that ultimately result in devastating pediatric diseases. Interacting closely with Dravet syndrome patient families conveys the urgency and importance of this translational work to everyone in my lab.
Dravet Syndrome is largely intractable – meaning that there are few drugs that effectively treat this disease. Our experiments, especially those using human-induced pluripotent stem cell neurons from patients with Dravet Syndrome (in collaboration with Jack Parent and Miriam Meisler), will hopefully lead to the development of novel therapeutics.
I’m proud to be the mother of two wonderful and successful daughters. We also have two crazy Schnoodles who think they’re our children.
Right after I first started my lab at U-M, I did a BLAST search via the National Center for Biotechnology Information (NCBI) for cDNAs that were similar to one of our newly cloned Na+ channel beta subunits. This was during the very early years of NCBI when you had to submit your search request manually to a person at a window who ran it and handed you back a printout the next day. My printout came back with a long list of genes that belonged to the immunoglobulin superfamily of cell adhesion molecules. No ion channel genes were present. I took a look at the results, immediately thought that I had mistyped something (obviously, a Na+ channel subunit could not be a cell adhesion molecule), and planned to redo the search the next day. In the middle of the night, I suddenly sat up in bed with a eureka revelation! Long story short, Na+ channel beta subunits are cell adhesion molecules and this discovery opened up a new field in ion channel biology. It just goes to show you – keep your mind open to ideas that are “impossible!”
I’m very fortunate to have a number of fantastic mentors. Two really stand out. The first is my postdoctoral mentor, Dr. Bill Catterall, at the University of Washington. He is truly the greatest scientific thinker, innovator, speaker, and writer that I’ve ever known. The second is our own Dr. Miriam Meisler at U-M. She is a true role model and mentor in every sense of the word and has had a tremendous influence on my scientific success and ability to balance work with family life.
My dad is a retired surgeon and, naturally, that’s exactly what I wanted to be. I worked in his medical office, made rounds in the hospital, and watched surgeries in the OR (of course, this was before HIPAA laws!). However, as a pre-med at Washington University, I had the opportunity to do undergraduate research in a biochemistry lab – and I was hooked!! I changed trajectories and went to graduate school. I’m not sure that my dad has ever gotten over it.