Zheng Fan Homepage

Zheng Fan Ph.D.
Professor

Department of Physiology

TELEPHONE:

(901) 448-2872
FAX: (901) 448-7126
E-MAIL: zfan@physio1.utmem.edu

Education

Ph.D., Tokyo Medical and Dental University, Japan, 1992

Postdoctoral Training, University of Chicago, Illinois, 1992-3

Research Background and Overview

ATP plays a pivotal role in the energy economy of the cell. Additionally, in many cell types such as islet b -cells of pancreas and muscle cells, ATP has important roles in transducing cellular signals which involve a particular type of potassium channel called ATP-sensitive potassium channel. In islet b -cells, for example, insulin release which occurs in response to hyperglycemia is mediated by a remarkable inhibition of ATP-sensitive potassium channel. My laboratory is currently working on several interrelated projects concerned with improving our understanding of the molecular basis for the biophysical activity of this channel, as well as increasing our appreciation of how energy metabolism interfaces with cellular processes through this channel under physiologic and pathophysiologic circumstances. The second focus of our research is on the regulatory roles of membrane phospholipids in modulating inwardly rectifying potassium channels including ATP-sensitive potassium channel. This research was built on our previous pioneering studies in this area. Currently we are interested in the cellular and molecular processes associated with, or dependent upon, this regulatory mechanism, and their physiologic relevance. Particular interest has been given to the role of this regulation in cardiac ischemia and myocardial protection.

Current Techniques Utilized

1. Methods of Electrophysiology: Patch-clamp recordings (whole-cell/single-channel configurations), voltage-clamp of Xenopus oocytes expressing ion channels translated from injected cRNA, single-channel recording in planar lipid bilayer, fluorescent measurement of cross-membrane ion flex.

2. Methods of Molecular Biology: Site-directed mutagenesis, cloning of cDNA, analysis of mRNA expression using Northern blotting/quantitative RT-PCR/RNAase protection.

3. Methods of Protein Biochemistry: Chromatography purification of membrane proteins, detection of proteins using immunoblotting/immunoprecipitation, reconstitution of membrane proteins into planar lipid bilayer/protoliposomes.

4. Methods of Lipid Biochemistry: Thin layer chromatography

5. Methods of Cell Biology: Cell culture, transfection/infection of mammalian cells/insect cells, immunostaining and confocal visualization of protein distribution in cultured cells.

Current Funding Status

2003-2007 Principal Investigator on RO1 from National Institute of Heart, Blood and Lung. “Phosphoinositides and ATP-Sensitive K+ Channels in Heart”

Selected Recent Publications

1. Gao L., Mi X., Paajanen V., Wang K., and Fan Z. (2005) From the Cover: Activation-coupled inactivation in the bacterial potassium channel KcsA. Proc Natl Acad Sci U S A. (via track II) 102:17630-17635

2. Gosmanov A.R., Fan Z., Mi X., Schneider E.G., and Thomason D.B. (2004) ATP-sensitive potassium channels mediate hyperosmotic stimulation of NKCC in slow-twitch muscle. Am. J. Physiol (Cell Physiol) 286:C586-595

3. Yang Y., Cui Y., Wang W., Zhang L., Bufford L., Sasaki S., Fan Z., Nishimura H. (2004) Molecular and functional characterization of a vasotocin-sensitive aquaporin water channel in quail kidney. Am. J. Physiol. (Regul Integr Comp Physiol) 287:R915-924

4. Fan Z., Gao L., and Wang W. (2003) Phosphatidic acid stimulates cardiac KATP channels like phosphatidylinositols, but with novel gating kinetics. Am. J. Physiol (Cell Physiol). 284: C94-C102

5. Wang C., Wang K., Wang W., Cui Y., and Fan Z. (2002) Compromised ATP binding as a mechanism of phosphoinositide modulation of ATP-sensitive K+ channels. FEBS Lett. 532:177-182

6. Cui Y., and Fan Z. Mechanism of Kir6.2 channel inhibition by sulfhydryl modification: pore block or allosteric gating? (2002) J. Physiol. 540: 731-741

7. Cui Y., Wang W., and Fan Z. (2002) Cytoplasmic vestibule of the weak inward rectifier Kir6.2 potassium channel. J. Bio. Chem. 277: 10523-10530

8. Nishimura H., Fan Z., and Zheng L. (2001) Renal handling of water in vertebrates. Perspective in Comparative Endocrinology: Unity and Diversity. Goos H.J.Th et al (Ed.) 733-742

9. Fan Z., and Neff, R.A. (2000) Susceptibility of native and cloned ATP-sensitive K+ channel to cell stress as examined by photoirradiation. J. Physiol. 529:707-721

10. Chutkow, W.A., Makielski J.C., Nelson, D.J., Burant C.F., and Fan Z. (1999) Alternative splicing of sur2 Exon 17 regulates nucleotide sensitivity of the ATP-sensitive potassium channel. J. Bio. Chem. 274:13656-13665

Revised 07/06