Dr. Engelman for his Ph.D. studied the relationship between Abelson murine leukemia virus protein tyrosine kinase activity and pre-B cell transformation. For his postdoc he studied with Drs. Robert Craigie and Kiyoshi Mizuuchi at the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. This work determined that (1) HIV integrase cleaves and joins DNA via one-step transesterification reactions, (2) a protease resistant central domain of integrase, called the catalytic core domain (CCD), harbors an invariant D,D-35-E motif that comprises the enzyme active site, and (3) integrase functions as a multimer, with the N-terminal domain of one integrase molecule working in trans with the CCD of a separate integrase protomer within the multimer. Dr. Engelman has continued to focus on HIV integration since starting his DFCI/HMS laboratory, expanding approaches to include structural biology and genome-wide mapping of integration sites within cellular chromatin. Such efforts have yielded novel X-ray crystal, NMR, and single-particle cryo-EM structures, elucidated the roles of virus-host interactions in HIV-1 trafficking and integration targeting mechanisms, and shed light on the mechanisms of action of clinical integrase strand transfer inhibitors (INSTIs) and preclinical allosteric integrase inhibitors (ALLINIs)