University of Wisconsin–Madison

Cynthia Czajkowski, PhD

Vilas Distinguished Achievement Professor, Department of Neuroscience

cmczajko@wisc.edu

608-265-5863

9503 Wisconsin Institutes for Medical Research
1111 Highland Avenue
Madison, WI 53705

Cynthia Czajkowski

Research Interests

The major focus of the lab is on understanding the function and structure of the GABA-A receptor. GABA-A receptors are the major inhibitory neurotransmitter gated-ion-channels in the brain. While GABA controls the opening of the anion-conducting channel, GABA-A receptor function is modulated by a variety of clinically important classes of drugs, including benzodiazepines, barbiturates, volatile anesthetics, neuroactive steroids and alcohol. Clinically, benzodiazepines, barbiturates and neuroactive steroids are used in the treatments of epilepsy, anxiety and panic disorders as well as other psychiatric illnesses. Recently, mutations in the GABA-A receptor have been linked to human epilepsy. Using computational modeling, protein chemistry, electrophysiology and molecular biological approaches, we are mapping and identifying the amino acid residues that form the binding sites for GABA as well as for therapeutic drugs that bind to the receptor. In addition, we are examining how mutations associated with human epilepsies alter GABA-A receptor function. We are also interested in examining the assembly and trafficking of the receptor and how interactions with other proteins modulate GABA-A receptor function.

Honors & Awards

  • 2012 University of Wisconsin- Vilas Distinguished Achievement Professor
  • 2008 Dr. Brenda Pfaehler Award of Excellence, TRIO program for mentoring undergraduate students from underrepresented backgrounds
  • 2004 College de France:Distinguished Lecturer
  • 2001 The National Alliance for Research on Schizophrenia and Depression, Independent Investigator Award
  • 1996 Burroughs Wellcome Fund, New Investigator Award

Selected Publications

(Find further publications on PubMed)

  • Laha, K.T., Ghosh, B and CZAJKOWSKI, C. (2013) Macroscopic Kinetics of Pentameric Ligand Gated Ion Channels: Comparisons between Two Prokaryotic Channels and One Eukaryotic Channel. PLoS ONE 8(11): e80322. doi:10.1371/journal.pone.0080322
  • Dellisanti CD, Ghosh B, Hanson SM, Raspanti JM, Grant VA, Diarra GM, Schuh AM, Satyshur K, Klug CS and CZAJKOWSKI C (2013). Site-directed spin labeling reveals pentameric ligand-gated ion channel gating motions. PLoS Biol 11(11): e1001714. (Paper highlighted in editor’s weekly pick)
  • Ghosh B and CZAJKOWSKI C (2013). Propofol binding to the resting state of theGloeobacter violaceusligand gated ion channel (GLIC) induces structural changes in the inter and intra-subunit trans-membrane domain (TMD) cavities.J. Biol. Chem. 288: 17420-17431.
  • Venkatachalan SP and CZAJKOWSKI C (2012). A structural link between the GABA-A receptor’s agonist binding site and innerb-sheet governs channel activation and allosteric drug modulation.J. Biol. Chem. 287: 6714-6724 PMCID: PMC3307325
  • Dellisanti CD, Hanson SM, Chen L and CZAJKOWSKI C (2011). Packing of the extracellular domain hydrophobic core has evolved to facilitate pentameric ligand-gated ion channel function.J. Biol. Chem. 286: 3658-3670.PMCID: PMC3030369