For a few months, Palade worked under Robert Chambers at New York University. Then he met Albert Claude at a lecture on electron microscopes and was invited to take up a two-year visiting investigator fellowship at the Rockefeller Research Institute.

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Here, Palade joined distinguished researchers like James Murphy, George Hogeboom, Walter Schneider, Keith Porter and Philip Siekevitz. He worked on cell fractionation, discovered techniques to break cell membranes and separate cell components using a centrifuge and to prepare specimens for study under the electron microscope. He studied the
mitochondria and the structure and function of ribosomes. Ribosomes were then known as microsomes and had earlier been identified by Albert Claude. Palade discovered that ribosomes were independent of the mitochondria, had a high content of
RNA and functioned as cell protein-producing power plants. This led to microsomes being renamed as ribosomes.
Palade took US citizenship in 1952. After 27 years at the Rockefeller Research Institute, he, in 1973, became Chairman of the Cell Biology Department at the Yale University Medical School. He spent the next 17 years researching how defective protein production in cells affected health.
In 1990, Palade moved to the University of California, San Diego (UCSD), where he was Professor of Medicine in Residence (Emeritus) in the Department of Cellular & Molecular Medicine. He was also a Dean for Scientific Affairs (Emeritus), in the School of Medicine at La Jolla, California, and a member of the UCSD Cancer Center Glycobiology Program.
He retired in 2001 at the age of 89, but remained a consultant (advisor) to the vice chancellor for Health Sciences and the dean of the UCSD School of Medicine until 2008. In his honor, there is a George E. Palade Endowed Chair at the UCSD.
Palade contributed articles to leading science journals and, apart from the Nobel Prize, received various other honors and awards.