He received his undergraduate, medical and doctorate degrees from Brown University, Providence, USA. He began studying natural killer (NK) cells for his doctoral dissertation in the laboratory of Christine Biron. After completing training as a paediatrician at The Children's Hospital of Philadelphia, J. Orange trained in immunodeficiencies at Boston Children's Hospital, Boston, USA, with Raif Geha. He then performed postdoctoral work on the biochemistry and cell biology of NK cells with Jack Strominger at Harvard University, Boston, USA. Since 2003, he has been running his own laboratory focusing on the NK-cell immunological synapse and insights that can be obtained from human genetic immunodeficiencies.