Department of Pharmacology
What we do:
My lab studies the cell biology and physiological effects of ion channel regulation.
How we got here:
While I was a post-doc, my colleagues and I were the first to discover that a voltage gated channel (Kv1.2) could be regulated by tyrosine phosphorylation. This innovative finding, published in Cell, was the first to link voltage gated channel regulation with many of the cellular mechanisms previously thought to not be significant players in the regulation of voltage gated ion channels. Indeed, this insight led directly to the discoveries that are at the foundation of my lab’s current focus on understanding the links between the molecular and cell biology of ion channel regulation with the effects of that regulation on neurophysiology and ultimately on behavior.
Where we are:
I started my lab in 1999, we pursued the idea that Kv1.2 regulation by tyrosine kinases involved the cytoskeleton. That led to our first publication identifying the action binding protein cortactin as a key regulator of Kv1.2. That novel finding was important because cortactin’s role in protein trafficking hinted at the possibility that endocytosis might be involved in regulating Kv1.2. My lab was subsequently the first to report that a voltage gated potassium channel’s function is regulated by its endocytic trafficking at the plasma membrane. Since then we have used a range of techniques, including flow cytometry, microscopy, biochemistry, molecular biology, and mass spectrometry, to characterize many of the molecular and cellular mechanisms of Kv1.2 regulation using model cell systems such as HEK293 cells.
The discovery that Kv1.2 is regulated by endocytosis was an important scientific finding, but it also conferred a tremendous technical advantage for studying Kv1.2 trafficking in the brain. We have therefore embarked on a new research effort to understand how native Kv1.2 is regulated in the brain. Our focus has been on the cerebellum because Kv1.2 is expressed to its highest levels in this part of the brain, and because the cellular anatomy of the cerebellum as well as the extensive body of research on cerebellar mediated learning makes it particularly well suited for studying how Kv1.2 regulation affects brain function and ultimately behavior.
What it means for you:
I am dedicated to offering the best possible training experience for my graduate students. My previous students have gone on to post-doctoral positions in prestigious labs at Stanford University and the Vollum Institute, careers in industry and faculty positions of their own. Because we study trafficking of ion channels in neurons, our work is a mix of cell biology and neuroscience.
Students in my lab therefore have the opportunity immerse themselves in a wide range of scientific areas while having the chance to learn many cutting edge techniques. For example, one project in my lab that might interest a rotation student is our effort to, for the first time; quantitatively identify stimulus induced monoubiquitylation of specific sites within Kv1.2 using the rat brain slice preparation and mass spectrometry. Another involves quantification of Kv1.2 trafficking of Kv1.2 at single synapses in rat brains using brain slices and multi photon microscopy. I am also committed to nurturing independence and creativity, so if you come up with an interesting experiment of your own relating to our work, you would be encouraged to try it.
Last modified December 05 2012 03:57 PM