University of Southern California

USC Neuroscience

Robert A. Farley

Professor Physiology and Biophysics, Biochemistry and Molecular Biology

Research Topics

  1. Transport protein biophysics
  2. Na, K-ATPase
  3. Neurotransmitter transport
  4. Peptide transport
  5. Protein structure
  6. Membrane proteins
  7. Molecular dynamics simulations

Research Overview

The primary interest of our lab is to understand the mechanisms that cells have developed to move ions and small molecules across cell membranes. Ion gradients of sodium and potassium underlie all electrical activity in cells, and in one project we are concerned with the structure and mechanism of Na,K-ATPase, the protein that catalyzes the active transport of these ions and establishes and maintains their transmembrane electrochemical potential gradients. In another line of investigation, we are studying the mechanisms of serotonin and GABA transport by neuronal serotonin and GABA transporters. These transporters are members of a class of proteins that couple neurotransmitter uptake to the transport of sodium ions, and often other ions as well, and we are working to understand how interactions among these different substrates and the proteins lead to their transport. The serotonin transporter, in particular, also exhibits characteristics of both an alternating access transporter and an ion channel, and we are interested to know how this observation can be explained. A third area of interest in our lab is the transport of small peptides across the intestinal epithelium. The transporter for these peptides, PepT1, recognizes and transports all combinations of di- and tri-peptides, but does not transport individual amino acids. Because PepT1 also transports certain peptide-drug conjugates and some small antibiotics, it is an attractive target for prodrug development designed to facilitate the convenient oral delivery of pharmaceuticals.

Our research into the structure and mechanisms of transport of each of these transporters has historically used techniques of membrane protein biochemistry, spectroscopy, electrophysiology, and molecular biology. As more atomic level structures of transport proteins have become available, however, we have moved primarily to using molecular dynamics simulations of these transporters as a tool to elucidate mechanistic details that are defined by and constrained by the protein structures.

Contact Information

Web Site:
Farley lab at USC
E-mail:
rfarley@usc.edu
Office Location:
MMR 250
Office Phone:
(323) 442-1240
Lab Location:
MMR 218
Lab Phone:
(323) 442-1241
Fax:
(323) 442-2283

Education

  • B.A., Hofstra University, 1970.
  • Ph.D., University of Rochester, 1975.

Research Images

Research Image Research Image

Selected Publications

View a complete PubMed search

View a complete Google Scholar search

Pyrko P, Kardosh A, Liu YT, Soriano N, Xiong W, Chow RH, Uddin J, Petasis NA, Mircheff AK, Farley RA, Louie SG, Chen TC, Schonthal AH. (2007) Calcium-activated endoplasmic reticulum stress as a major component of tumor cell death induced by 2,5-dimethyl-celecoxib, a non-coxib analogue of celecoxib. Mol Cancer Ther. 6(4):1262-75. -PubMed

Nagy AK, Kane DJ, Tran CM, Farley, RA, and Faller LD. (2005) Evidence calcium pump binds magnesium before inorganic phosphate. J. Biol. Chem. 280: 7435-7443. -PubMed

Xu G, Kane DJ, Faller LD, and Farley RA. (2004) The role of loop 6/7 in folding and functional performance of Na,K-ATPase. J. Biol. Chem. 279: 45594-45602. -PubMed

Faller LD, Nagy AK, Kane DJ, and Farley RA. (2003) Mechanism of phosphoryl group transfer. Ann. N.Y. Acad. Sci. 986: 275-277. -PubMed

Li M, Farley RA, and Lester HA. (2002) Voltage-dependent transient currents of human and rat 5-HT transporters (SERT) are blocked by HEPES and ion channel ligands. FEBS Lett. 513: 247-252. -PubMed

Muller-Ehmsen J, Juvvadi P, Thompson CB, Tumyan L, Croyle M, Lingrel JB, Schwinger RH, McDonough AA, and Farley RA. (2001) Ouabain and substrate affinities of human Na,K-ATPase alpha(1)beta(1), alpha(2)beta(1), and alpha(3)beta(1) when expressed separately in yeast cells. Am. J. Physiol. Cell Physiol. 281: C1355-C1364. -PubMed

Wang J, Velotta JB, McDonough AA, and Farley RA. (2001) All human Na(+)-K(+)-ATPase alpha subunit isoforms have a similar affinity for cardiac glycosides. Am. J. Physiol. Cell Physiol. 281: C1336-C1343. -PubMed

Farley RA, Elquza E, Muller-Ehmsen J, Kane DJ, Nagy AK, Kasho VN, and Faller LD. (2001) 18O-exchange evidence that mutations of arginine in a signature sequence for P-type pumps affect inorganic phosphate binding. Biochemistry 40: 6361-6370. -PubMed

Farley RA, Schreiber S, Wang SG, and Scheiner-Bobis G. (2001) A hybrid between Na(+)-K(+)-ATPase and H(+)-K(+)-ATPase is sensitive to palytoxin, ouabain, and SCH28080. J. Biol. Chem. 276: 2608-2615. -PubMed

Li M, Farley RA, and Lester HA. (2000) An intermediate state of the gamma-aminobutyric acid transporter GAT1 revealed by simultaneous voltage clamp and fluorescence. J. gen. Physiol. 115: 491-508. -PubMed