Cynthia Czajkowski, Ph.D. Professor Department of Physiology czajkowski@physiology.wisc.edu Czajkowski's home page

Research Description:

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.

Selected Publications: Articles on Pubmed

• Hanson SM and Czajkowski C. (2008). Structural mechanisms underlying benzodiazepine modulation of the GABA-A receptor. J Neurosci. 28:3490-3499.
  
  
• Mercado J and Czajkowski C. (2008). GABA and pentobarbital induce different conformational rearrangements in the GABA-A receptor alpha1 and gamma 2 pre-M1 regions. J Biol Chem. 283:15250-15257.
  
  
• Sharkey LM and Czakowski C. (2008). Individually monitoring ligand-induced changes in the structure of the GABA-A receptor at benzodiazepine binding site and non-binding site interfaces. Mol Pharmacol. 74:1-10.
  
  
• Venkatachalan S and Czajkowski C. (2008). A conserved salt-bridge critical for GABA-A receptor function and loop C dynamics. PNAS. In press.
  
  
• Kloda JH and Czajkowski C. (2007). Agonist-, antagonist-, and benzodiazepine-induced structural changes in the alpha1 Met113-Leu132 region of the GABAA receptor. Mol Pharmacol. 71:483-493. PMID 17108261
  
  
• Sancar F, Ericksen SS, Kucken AM, Teissere JA, and Czajkowski C. (2007). Structural determinants for high-affinity zolpidem binding to GABA-A receptors. Mol Pharmacol. 71:38-46. PMID 1701261
  

View More Publications

Lab Members:

• Andrew Boileau, Ph.D., Associate Research Scientist
  
• Lisa Sharkey, B. S. Graduate Student in Neuroscience Training Program
  
• Feyza Sancar, B. S., Graduate Student in Neuroscience Training Program
  
• Jose Mercado, B.S., Graduate Student in Neuroscience Training Program
  
• Amy Kucken, B. S., Research Specialist
  
• Jeremy Bushman, Undergraduate Research
  
• Whitney Pafford, Undergraduate Research
  

Past lab members:
Post-doctoral Trainees:

• Nicholas Cozzi, Ph.D., Currently: Asst. Prof., Dept. of Pharmacology, School of Medicine East Carolina University, Greenville, NC 27858
  
• David Wagner, Ph.D., Currently: Asst. Prof. at Marquette University, Milwaukee, WI
  
• Glen Newell, Ph.D., Currently: Postdoctoral Trainee in the lab of Dr. Bev Orser, University of Toronto, Canada

Pre-doctoral Trainees:

• Jeremy Teissere (1997-2001) Currently: Postdoctoral trainee in the lab of Dr. Randy Hall (Emory University), Asst. Prof. at Muhlenberg College, NJ starting 9/1/03.
  
• Jessica Holden Kloda (1998-2003) Previously: Postdoctoral trainee
  Currently: Postdoctoral trainee at NIH, (Maryland)