Richard E. Pagano passed away recently at age 66. Pagano was known for his innovative application of lipid biophysics and imaging technology to understanding the molecular organization of cell membrane lipids.
Photo credit: David Marks
Richard E. “Dick” Pagano, a pioneer scientist in lipid cell biology, recently died at the age of 66. At the time, he was the head of a vibrant and productive laboratory in the department of biochemistry and molecular biology at the Mayo Clinic College of Medicine in Rochester, Minn. An overarching theme of Dick’s research for the past 45 years was the innovative application of lipid biophysics and imaging technology to understanding the molecular organization of cell membrane lipids.
Dick trained with Thomas E. Thompson at the University of Virginia, where he received his doctoral degree in biophysics, studying ion permeability in model membranes. He continued to work with model membrane systems during his postdoctoral work with Norman L. Gershfeld at the National Institutes of Health and then with Israel R. Miller at the Weizmann Institute. During a brief fellowship in Dennis Chapman’s lab at the University of Sheffield, Dick performed some of the first direct measurements confirming that gel and liquid phases could coexist in the same membrane.
Dick started his own lab in 1972 at the Carnegie Institution department of embryology in Baltimore, Md., where he worked for more than two decades before moving to the Mayo Clinic. It was at Carnegie that Dick first applied his experience using model membranes to addressing the central and largely unanswered questions in the cell biology of membrane lipids. The combination of lipid biophysical and cell biological approaches proved extremely fruitful. Dick’s initial work elucidated mechanisms of interaction between artificial membrane vesicles and cells, which has relevance to the pharmacologic use of liposomes. His work also provided an early method of introducing labeled lipids into the outer leaflet of the plasma membrane. Ultimately, the creative use of lipid probes incorporated into cell membranes to study lipid metabolism and trafficking would become the signature of Dick’s scientific career.
Dick pioneered the use of lipids in which a native acyl chain was replaced with a short chain fluorescent analogue that readily incorporated into cell membranes and faithfully mimicked the behavior of the natural lipid equivalent. The Pagano lab created dozens of fluorescent lipid probes, which enabled several key advances, including tracking membrane lipid transport, labeling the Golgi apparatus of living cells, identifying intracellular compartments involved in sphingolipid metabolism, measuring transbilayer movement of aminophospholipids and demonstrating that sphingolipids regulate several membrane transport pathways.
Among these milestones, a fluorescent lactosylceramide analogue enabled the Pagano lab to discover a common mechanism of action that underlies sphingolipid storage diseases, namely, that cholesterol accumulation diverts internalized sphingolipids from the Golgi recycling pathway to lysosomes where they accumulate. This allows fluorescent lactosylceramide to be used as a sensitive diagnostic tool to identify patients with defects in sphingolipid metabolism. Dick’s work in this area also led to the identification of several potential therapeutic options for treatment of sphingolipidoses, which have been verified to reverse the trafficking defect in vitro and in animal models of Niemann-Pick disease, type C.
During his career, Dick trained more than 50 students and postdoctoral fellows, many of whom are current leaders in the field of lipids that he pioneered. He successfully trained scientists largely by example since, in demeanor and practice, Dick was first and foremost a bench scientist. The environment in the Pagano laboratory was one where spirited discussion was encouraged, where everyone’s opinion was considered and each piece of data scrutinized. Discussions occasionally became heated, but this was tempered by Dick’s dry humor and desire to get the story right. Dick appreciated the joy of discovery, including the rigor and creativity that are needed to be an outstanding scientist. He is deeply missed by colleagues, friends and family.
Michael Koval (email@example.com) is an associate professor of medicine and cell biology at the Emory University School of Medicine.