He began his research career at the University of Buenos Aires, in the laboratory of Eduardo de Robertis, a founder of modern cell biology, where he developed skills in electron microscopy.
His early work studied co-translational targeting of ribosomes to the endoplasmic reticulum and helped establish the hypothesis that signal peptides direct protein traffic to cellular compartments.
With a group of young associates (Nica Borgese, Mark Adelman, and Gert Kreibich), collaborating with Gunter Blobel, he continued research on the mechanism that ensures the co-translational translocation and vectorial discharge of nascent polypeptides into and across the endoplasmic reticulum membrane.
For a discussion of the genesis and evolution of the signal hypothesis see LaBonte, 2017[14] In the 1971 paper, Blobel and Sabatini proposed that “all mRNAs to be translated on bound ribosomes have a common feature, such as several codons near their 5’ end, not present in mRNAs which are to be translated on free ribosomes” and that “the resulting common sequence of amino acids near the N-termini of the nascent chains, or a modification of it, would then be recognized by a factor mediating the binding to the membrane."
[18][19][20] In 1972, Sabatini moved his laboratory to the New York University School of Medicine to become the chair of the Department of Cell Biology,[21] where he assembled a group that focused on the study of membrane and organelle biogenesis.
He was awarded the Charles Leopold Mayer Prize (1986) and the Grande Médaille (2003) by the French Academy of Sciences, and in 2006 he was named a Chevalier de la Légion d’honneur.