James E. Hall
Professor, Physiology & Biophysics
School of Medicine
PH.D., University of California, Riverside, 1968
B.A., Pomona College, 1963, Astronomy
Phone: (949) 824-5835, 6676
Fax: (949) 824-3143
University of California, Irvine
D337 MED SCI I
Mail Code: 4560
Irvine, CA 92697
Structure and function of junctional channels; Reconstitution of channel proteins in lipid bilayers. Gap junctions. Aquaporins. Lens.
We're trying to understand fluid balance in the lens. This is scientist-speak for how cataracts form. The lens is a slow-living low-energy organ that uses very little oxygen. After all it just has to sit there and let you see! The down side of this is that the lens has no energy reserves available to correct things that go wrong, even little things. Most of the things that can go wrong with fluid balance result in cataracts.
Our aim is to understand the mechanisms which normally operate in the lens to produce proper fluid balance. Our hope and belief is that this will lead us to better methods for preventing or removing cataracts. Interestingly there are no known tumors of the lens.
The overall goal of our research is to understand the role of water channels and gap junction channels in the fluid balance of the ocular lens. The lens must remain transparent, refractile and flexible in order to focus an image on the retina and provide for accommodation. These requirements impose severe restrictions on the physiology of the lens the most obvious of which is a lack of blood vessels. Absence of vascular circulation in turn requires that the lens itself somehow generate an internal circulation, as diffusion is not sufficient to supply its metabolic needs. How this circulation is generated and regulated is the subject of our research. We are concentrating on AQP0, a water channel protein found only in the lens Defects in AQP0 cause cataracts in both mice and humans. Our lab has found that AQP0 water permeability is controlled by changes in pH and Ca2+ and we are attempting to demonstrate the physiological relevance of this sort of regulation using a transgenic mice lacking regulation competent protein.
Amyloid beta protein has long been investigated as the major suspect as a causative agent for Alzheimer’s disease, but the mechanisms by which it may act have proven illusive, multiple and confusing. Recent collaborative experiments between Charlie Glabe’s lab and Jim Hall’s lab suggest there may be a way out of this dilemma. Glabe’s lab has developed techniques for synthesizing amyloid beta protein and, more importantly, methods for isolating the particular physical aggregation and conformational states of the peptide in pure form. In preliminary blind experiments, Yuri Sokolov in Hall’s lab found that only one state of the peptide, the micelle form, induces a conductance in planar lipid bilayers. This micellar species also seems to be the physical form actually responsible for the early pathology of the disease. Soluble monomers and fibrils, have no effect. In addition, antibodies specific to the micelle physical form prevent the conductance increase.
Our conductance measurements suggest that amyloid oligomers exert their toxic effects by reducing the dielectric barrier for ions to cross the lipid bilayer, and recent neutron reflectometry data support this view. If it proves correct, it should open the way to investigating several novel avenues for Alzheimer’s treatments.
Kayed,R.; Sokolov,Y.; Edmonds,B.; McIntire,T.M.; Milton,S.C.; Hall,J.E.; Glabe,C.G. Permeabilization of Lipid Bilayers Is a Common Conformation-dependent Activity of Soluble Amyloid Oligomers in Protein Misfolding Diseases. J. Biol. Chem. 279: 46363- 46366 (2004)
Karinne Németh-Cahalan, Kati Kalman and James E. Hall. Molecular basis of pH and Ca2+ regulation of aquaporin water permeability. Journal of General Physiology. 123: 573-580 (2004)
Derek L. Beahm and James E. Hall, Opening Hemichannels In Non-Junctional Membrane Stimulates Gap Junction Formation. Biophys. J., 86:781-796 (2004).
Rickey L. Rivers, Robert M. Dean, Grischa Chandy, James E. Hall, Daniel M. Roberts and Mark L. Zeidel. Functional analysis of Nodulin 26, an Aquaporin in soybean root nodule. J. Biol. Chem. 272:16256-16261 (1997)
Chandy, Grischa, Guido A. Zampighi, Michael Kreman, and James E. Hall. Comparison of the water transporting properties of MIP and AQP1. J. Membrane Biol. 159:29-39 (1997)
Alan Miller and James E. Hall. Junctional permeability measurements in the embryonic chick lens. Experimental Eye Research 62:339-49 (1996)
Jayashree Aiyar, Jane M. Withka, James P. Rizzi, David H. Singleton, Glen C. Andrews, Wen Lin, James Boyd, Doug Hanson, Mariella Simon, Brent Dethlefs, Chao-Lin Lee, James E. Hall, George Gutman, George Chandy. Topology of the pore region of a K+ Channel revealed by the NMR-derived structures of scorpion toxins. Neuron 15:1169-1181 (1995)
Guido A. Zampighi, Michael Kreman, Kathyrn J. Boorer, Donald D. F. Loo, Francisco Bezanilla, Grischa Chandy, James E. Hall, and Ernest M. Wright. A method for determining the unitary functional capacity of cloned channels and transporters expressed in Xenopus laevis oocytes. J. Memb. Biol. 148:65-68 (1995)
Society of General Physiologists
Structural Biology and Molecular Biophysics
Cellular and Molecular Biosciences