His wide-ranging studies of protein structure have contributed insights to viral architecture, DNA–protein recognition, and cellular signaling.
Harrison has made important contributions to structural biology, most notably by determining and analyzing the structures of viruses and viral proteins, by crystallographic analysis of protein–DNA complexes, and by structural studies of protein-kinase switching mechanisms. The initiator of high-resolution virus crystallography, he has moved from his early work on tomato bushy stunt virus (1978) to the study of more complex human pathogens, including the capsid of human papillomavirus, the envelope of dengue virus, and several components of HIV. He has also turned some of his research attention to even more complex assemblies, such as clathrin-coated vesicles.  He led the Structural Biology team at the Center for HIV/AIDS Vaccine Immunology (CHAVI) when it received National Institute of Allergy and Infectious Diseases (NIAID) funding  of around $300 million to address key immunological roadblocks to HIV vaccine development and to design, develop and test novel HIV vaccine candidates.