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In Memoriam: Joseph Frederick Hoffman, PhD

June 06, 2022

Joseph Frederick Hoffman, PhD, Eugene Higgins Professor Emeritus of Cellular and Molecular Physiology, passed away on May 19, 2022 at age 97. He was a tireless and dedicated researcher of red blood cells who published papers until he was 93.

Hoffman was born on March 7, 1925, in Oklahoma City, Oklahoma, where, like his two older brothers, he achieved the rank of Eagle Scout. He graduated from the University of Oklahoma in 1948 after earning both bachelor's and master’s degrees. He was then admitted to the graduate school of Princeton University where he attained a second master’s degree (1951) and a doctoral degree in physiology (1952). After completing his studies, he joined the faculty of Princeton’s Department of Biology and conducted studies at the Brookhaven National Laboratory.

He left Princeton in 1956 to pursue research work at the University of Cambridge and, in 1957, he was hired by Robert Berliner (future dean of Yale School of Medicine) who then was serving as the director of the Laboratory of Kidney and Electrolyte Metabolism at the National Institutes of Health. Hoffman came to Yale in 1965 to join the faculty of the Department of Physiology, serving as the department’s chair from 1967–1968 and from 1973–1979.

While at Princeton, Hoffman began his studies of the membrane permeability properties of red blood cells, which became his central focus through more than six decades of research. He was intrigued by the roles of ATP-driven ion pumps and ion channels in defining the ionic composition of a cell’s cytoplasm and in regulating cell volume. During the time he spent at Brookhaven, Hoffman met and formed a lifelong friendship with Daniel Tosteson (who later served as the dean of Harvard Medical School). Hoffman and Tosteson became close scientific collaborators and, in 1960, published a landmark paper in the Journal of General Physiology that described their “pump-leak” model. This mathematical formulation provided a theoretical framework that explained in predictive detail how the fluxes through ion pumps, channels, and transporters account for the distributions of ions across a cell’s plasma membrane and for the maintenance of stable cell volume in spite of osmotic forces that might be expected to produce cell swelling and lysis.

During his time at Yale, Hoffman continued to explore mechanisms of membrane transport and their role in determining cell shape. Hoffman and colleagues created highly versatile light-activated chemical probes that could be used to label ion transport proteins and to study the kinetic properties of ion transport processes. Although he formally closed his laboratory and became an emeritus professor in 2003, he remained passionately involved in the biology of red blood cells. His final two research papers, which explored the mechanisms through which red blood cells maintain their intriguing biconcave disc shape, were published in the Proceedings of the National Academy of Sciences in 2016 and 2018, when he was 91 and 93 years old. For his many accomplishments as a scientist and as a leader, Hoffman received numerous honors, including election to the National Academy of Sciences in 1981 and the American Academy of Arts and Sciences in 1984. He served as the president of the Biophysical Society and of the Society of General Physiologists, and he edited numerous books and journals. Hoffman was a very active participant in the intellectual life and communal spirit of the Department of Cellular and Molecular Physiology until he fell ill in early April of this year.

Hoffman’s survivors include his nephew, Richard E. Hoffman, MD (Molly), of Denver, CO; his nieces, Patricia Ann McNichols of Milwaukee, WI, Jill E. Tiernan (Thomas) of Dallas, TX, and Claudia Citkovitz (John Barnard) of Shutesbury, MA; his sister-in-law, Evgenia Citkowitz; and six great-nieces, as well as cousins and in-laws. He was pre-deceased by Elena Citkowitz, MD (Yale ’83), his wife of 41 years, and his two brothers, Edmund Hoffman and Henry Hoffman Jr.

Submitted by Robert Forman on June 06, 2022