Professor Lye has held more than SGD$13million in research grant as principal investigator to date. His research interests are in COVID-19, dengue and antimicrobial resistance. He has published more than 350 peer-reviewed manuscripts in journals such as NEJM, Lancet, JAMA, JAMA Oncology, Lancet Respiratory Medicine, Lancet Infectious Diseases, Lancet Microbe, Lancet Global Health, Annals Internal Medicine as well as Science, Nature Biotechnology, Nature Reviews Immunology, Nature Microbiology, Nature Communications, Science Translational Medicine, Journal Clinical Investigation and Journal Experimental Medicine.