Northwestern University Feinberg School of Medicine

Paul DeCaen Lab

Research

The DeCaen lab is located on the fifth floor of the Searle building in the Northwestern University Feinberg School of Medicine. Our facility houses several electrophysiology and state-of-the-art microscopes, along with various biochemistry and molecular biology equipment. We utilize these instruments with genetic tools to study ion channel function. In addition, our group has access to the core facilities at Northwestern, including the Nikon imaging facility.

Current Projects

We study the biophysics, pharmacology and physiology of ion channels. Currently we are focused on two divergent groups: voltage gated sodium channels (Nav) and Polycystin channels (also called Polycystic Kidney Disease Proteins, PKDs). Aside from these foci, we actively explore novel ion channels found in prokaryotic and eukaryotic cells with the goal of understanding their function in cell physiology.

Voltage Gated Sodium Channels

Navs conduct sodium ions into excitable cells like muscle and neurons, causing the cell membrane to depolarize on the microsecond time scale, a process essential for rapid communication in multicellular organisms. Potentially fatal conditions such as forms of epilepsy and cardiac arrhythmias arise when Navs are mutated.

With our collaborators, we continue to examine key questions:

  1. How do these transmembrane proteins sense electrical potential and change from nonconductive to conductive states?
  2. How do these transmembrane proteins select for sodium ions and not allow passage of the other ions present?
  3. What are the mechanisms of action of clinically relevant drugs such as Valproate and Lamotrigine, and where are their receptor sites?

Polycystin Channels and Primary Cilia

Mutations in PKD1 and PKD2 are associated with Autosomal Dominant Kidney Disease (ADPKD). ADPKD is one of the most common monogenetic diseases in mankind where progressive cyst formation results in kidney failure. Several members of the polycystins (PKD1, PKD1-L1, PKD2 and PKD2-L1) have been found in the primary cilia from cells of various tissues besides the kidney. The primary cilium is a solitary, small (5-15 mM in length) protuberance from the apical side of polarized cells.

With help from our collaborators, our research is directed to answer key questions:

  1. How do ADPKD mutations alter PKD2 function? Do some mutations ‘turned on’ while others ‘turn off ’ the PKD2 channel?
  2. How does PKD1/2 channel dysfunction result in cyst formation? Or conversely, what normal function do they serve for the primary cilium and how do PKDs maintain cell polarity?
  3. What are the receptor sites within PKD2s that can modulation its ion channel function and are they drug-able?

Publications

For a list of publications from this lab, see the principal investigator’s faculty profile.