Dalton Cardiovascular Research Center

University of Missouri

Silvia G. Bompadre, PhD

Research Interests

Structure, dynamics and function of CFTR channels

Research Description

The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that is regulated by phosphorylation and gated by ATP binding and hydrolysis. Mutations in the gene coding for CFTR result in the genetic disease cystic fibrosis (CF). CF is manifested by a defective chloride transport across the epithelial cells in various tissues such as respiratory, gastrointestinal, hepatobiliary, and reproductive tracts.

Dr. Bompadre research focuses on understanding how CFTR works at the molecular level and how mutations in CFTR cause defective functions. The final goal is to apply the acquired knowledge in therapeutic design for CF.  Combining patch-clamp (a single-molecule technique to study the function of ion channels in their native environment) with fluorescence spectroscopy techniques, such as single-molecule FRET, and molecular modeling studies are set to advance our understanding of the relationship between structure, dynamics and function for these channels.

Recently, Dr. Bompadre's studies focused on the mechanisms responsible for the dysfunction of the two most common disease-associated mutants, G551D-CFTR and ΔF508-CFTR.

Professional Background

• Obtained PhD in Physics from the University of Washington.
• Performed postdoctoral training in Physics at the University of Florida.
• Completed postdoctoral training in Electrophysiology at the University of Missouri-Columbia.
• Obtained funding from the National Institutes of Health (NIDDK) and the Cystic Fibrosis Foundation.

Selected Publications

• Jih K-Y., Li, M., Hwang T.-C., and Bompadre S.G. 2011.  “The most common cystic fibrosis associated mutation destabilizes the dimeric state of the nucleotide binding domains of CFTR”. J. Phys.  Under review. 
• Cai Z, Sohma Y, Bompadre SG, Sheppard DN, Hwang TC. Application of high-resolution single-channel recording to functional studies of cystic fibrosis mutants. Methods Mol Biol. 2011;741:419-41. (2011) 
• Yu YC, Miki H, Nakamura Y, Hanyuda A, Matsuzaki Y, Abe Y, Yasui M, Tanaka K, Hwang TC, Bompadre SG, Sohma Y.,Curcumin and genistein additively potentiate G551D-CFTR., J Cyst Fibros. 2011 Jul;10(4):243-52. Epub 2011 Mar 26., PMID: 21441077
• Miki, H., Zhou, Z., Li, M., Hwang, T.-C, and Bompadre, S.G. Potentiation of disease-associated CFTR mutants by hydrolyzable ATP analogs. J. Biol. Chem. 285:19967-19975 (2010).
• Wang X., Bompadre S.G., Li, Min, and Hwang T.-C. Mutations at the signature sequence of CFTR create a Cd(2+)-gated chloride channel. J Gen Physiol. 133(1):69-77 (2009).
• Bompadre S.G., Li, M. and Hwang T.-C.  Mechanism of G551D-CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) Potentiation by a High Affinity ATP Analog. J. Biol. Chem. 283: 5364-5369 (2008).
• Bompadre SG, and Hwang TC. CFTR: a chloride channel gated by ATP binding and hydrolysis. Acta Physiologica Sinica. 59 (4): 431-442. (2007).
• Bompadre, SG, Sohma, Y., Li, M., and Hwang, T.-C.G551D and G1349D, two CF-associated mutations in the signature sequence of CFTR, exhibit distinct gating defects. J. Gen. Physiol. 129, 285-298. (2007).
• Bompadre SG, Cho JH, Wang X, Zou X, Sohma Y, Li M, and Hwang TC.CFTR Gating II: Effects of nucleotide binding on the stability of open states. J.Gen. Physiol. 125: 377-394 (2005).
• Bompadre SG, Ai T, Cho JH, Wang X, Sohma Y, Li M, and Hwang TC.  CFTR Gating I: Characterization of the ATP-dependent gating of a phosphorylation-independent CFTR channel (DR-CFTR). J.Gen. Physiol. 125: 361-375 (2005).
• Ai T, Bompadre SG, Sohma Y, Wang X, Li M, Hwang TC. Direct effects of 9-anthracene compounds on cystic fibrosis transmembrane conductance regulator gating. Pflugers Arch. 449: 88-95 (2004).
• Ai T, Bompadre SG, Wang X, Hu S, Li M, and Hwang TC. Capsaicin potentiates wild-type and mutant cystic fibrosis transmembrane regulator chloride-channel currents. Mol Pharmacol 65:1415-1426 (2004).