While still at the graduate school, to support his studies, Novikoff worked as a part-time instructor at the new
Brooklyn College. His initial research focused on
experimental embryology, and soon his interest shifted to cell biology under the influence of Arthur Pollister. In 1938 he was awarded his PhD. He was not on good terms with the other teachers and the administration at Brooklyn College, such that his promotion was delayed for a year even after his new degree. He did a post-doc at the University of Wisconsin in 1946–1947. The two met at
Central Park in New York City to discuss their results. In 1955, now confident that the membranous particles were cell organelles, de Duve gave a hypothetical name "
lysosomes" to reflect their
digestive properties. That same year, after visiting de Duve's laboratory, using his own histochemical protocol Novikoff successfully produced the first real images (
electron micrographs) of the new organelle. In 1965 with de Duve, he confirmed the location of the
hydrolytic enzymes of lysosomes. Novikoff further established the importance of lysosomes in diseases. "It is largely due to Novikoff's bold and imaginative use of morphological techniques," de Duve praised him, "that lysosomes have come to be recognized in a broader biological context." de Duve went on to win the
Nobel Prize in Physiology or Medicine in 1974 for the discovery of lysosomes, but Novikoff's contributions were forgotten. It was at the
Ciba Foundation Symposium on Lysosomes held in London on 12–14 February 1963, that he explained this phenomenon in which organelles such as
endoplasmic reticulum,
ribosomes, mitochondria and other cell debris were degraded by
autolysis in the cytolysomes. Then the following speaker de Duve correctly identified that these organelles were lysosomes, and named them
autophagic vacuoles, and he introduced the term "
autophagy" for the process of such intracellular digestion. In 1962 he established for the first time the functional relationship between ER, Golgi and lysosomes. He specifically showed that smooth-surfaced derivatives of the ER fused with the Golgi membranes and the Golgi membranes in turn fused with lysosomes. He was the first to show that this GERL is responsible vesicular transport during synthesis and sorting of proteins. He gave this functional organisation an acronym GERL, for
Golgi-
endoplasmic
reticulum-
lysosome. Novikoff's further works became a milestone in understanding the importance of autophagy in diseases such as
cancer. He was the first to establish the type of
liver tumour, now known in his honour as "Novikoff hepatoma". In 1961 with Sidney Goldfischer, Novikoff developed a staining method for the
Golgi body using the enzyme nucleosidediphosphatase, by which they described the enzymatic property of the organelle for the first time. In 1969 they developed a staining technique (alkaline diaminobenzidine, or DAB) by which they studied the structure of another new organelle,
peroxisome, for the first time. In 1969 he gave the first clear-cut distinction between lysosomes and peroxisomes. In 1972, he and his wife discovered a new type of peroxisomes from the intestinal epithelium of rat, which they named "microperoxisome". His works in cell biology are best summed up in a textbook he wrote with his student Eric Holtzman,
Cells and Organelles, first published in 1970. ==Novikoff Affair==