In Memoriam: James E. Hall, PhD

James E. Hall, PhD, a former professor of physiology and biophysics at UC Irvine, died on Dec. 26, 2025, at the age of 84.

Hall received his bachelor's degree in astronomy from Pomona College, his master's degree and PhD in physics in 1970 under Leon Bruner at UC Riverside, and postdoctoral training under Professors Carver Mead and Max Delbruck at the California Institute of Technology. His research, spanning five decades, ranged from the first recordings of single-ion channel activity in lipid bilayer membranes to the fundamental properties of ion channels and water transport through cell membranes. Hall moved to Duke University in 1974 and established a reputation as an expert in the emerging field of ion channels. He then joined the faculty at UC Irvine in 1978, playing an important role in shaping the teaching and research programs in the School of Medicine.

Throughout his career, Hall made pivotal contributions to the mechanisms of 20-amino acid peptide antibiotic, alamethicin, which induced a strongly voltage-dependent conductance in both lipid bilayers and in cell membranes. His approach using synthetic variants of the naturally occurring peptide to investigate structure-function relations presaged the later method of site-directed mutagenesis, which has proven fruitful in dissecting voltage-gating mechanisms in mammalian sodium and potassium ion channels that underlie action potentials. Hall’s work was also influential in establishing a paradigm for biophysical approaches to studying channel proteins. During this early period of his research, he received an NIH research career development award and served on the Ion Channels NIH study section. 

His biophysical intuition and approaches led to numerous collaborative publications supported by multiple grants from NIH, the Alzheimer’s Association and the Hillblom Foundation. Among his collaborators were:

• Michael Cahalan (UC Irvine) inactivation of alamethicin incorporated into cell membranes; 
• Guido Zampighi (UCLA) properties of gap junction proteins reconstituted into lipid bilayers; 
• Anne Warner (University College, London) gap junctions in development; 
• Bernie Gilula (The Scripps Research Institute) gap junctions in keratinocyte differentiation; 
• The late Harry Haigler (UC Irvine) function of annexins to modulate the lipid properties of cells;
• Charles Glabe (UC Irvine) conductance effects of soluble amyloid oligomers; 
• Tom Schilling (UC Irvine) aquaporin water transport and adhesion in zebrafish lens; and
• Doug Tobias (UC Irvine) molecular dynamics simulation of water transport in Aquaporin 0.

Hall’s lab investigated the role of AQP0, a water channel in lens fiber cells, in the development of the ocular lens and the maintenance of its transparency. His group was the first to show that AQP0 water permeability is not fixed, but can be modulated by extrinsic changes in ionic composition and by calmodulin. The Hall lab found that changes in pH or in Ca2+ concentration alter the water permeability of AQP0. Subsequent experiments demonstrated that external histidines are responsible for the pH modulation and internal calmodulin for the Ca2+ modulation of AQP0 water permeability. Hall’s lab was able to make the normally pH-independent water permeability of AQP1 respond to pH by adding histidines in locations analogous to the positions in which histidines are found in AQP0. Importantly, the modulation of AQP0 water permeability may be associated with human cataract. The Hall lab showed that a defective form of AQP0 found in a strain of mouse that has a congenital cataract eliminates Ca2+ regulation when co-expressed with normal AQP0 in Xenopus oocytes, the best evidence available to date that Ca2+ modulation of AQP0 water permeability is important in the development of the lens. Hall’s lens work was continuously funded for 25 years by NIH grant EY05661-25, Structure and Function of Lens Channels.

Hall was a pioneer and recognized leader in the fields of ion and water transport across cell membranes. He was highly influential in applying the fundamental principles of physics to understand biological mechanisms. The faculty of the Department of Physiology and Biophysics have benefited greatly over the years from his generosity and scientific insight. Hall will long be remembered by his colleagues and by generations of medical and graduate students for his enthusiastic lectures on sensory physiology, electronics for biologists and the biophysics of ion channels. His unique style was designed to promote engagement and lifelong learning. Above all, Hall is remembered fondly as a warm and generous human being whose spirit enriched the lives of many. Apart from his many contributions to science, he had a full repertoire of jokes, limericks, and stories that brightened up many a faculty gathering. He will be deeply missed as a brilliant scientist, a dear friend and a wonderful colleague.

— Stephen H. White, PhD, and Michael D. Cahalan, PhD
Department of Physiology & Biophysics, UC Irvine School of Medicine