From 2007-2011 he coordinated an EC FP6 project on Approaches to Control multi-resistant Enterococci (ACE) and from 2011-2015 he was principal investigator and coordinator of the EC FP7 project designated Evolution and Transmission of Antibiotic Resistance (EvoTAR). His research group aims to unravel the genetic evolution, population and functional genomics of Enterococcus faecium and Enterococcus faecalis as well as E. faecium host-pathogen interactions. His group was the first that identified structure in the E. faecium population and described that strains from hospitalized patients were genetically distinct from animal isolates and human commensal isolates. He also published the first comparative genomics paper on E. faecium using comparative genomic hybridizations as well as whole genome sequencing that revealed that E. faecium has an open genome capable for frequently incorporating new DNA in its genome. Currently, his group is focussing on genome based epidemiology of multidrug-resistant pathogens, with a special focus reconstructing and tracking the spread of plasmids based on genome and metagenome sequence data. Furthermore, his group aims to decipher the processes and molecular mechanisms that contribute to colonization resistance against high density colonization of antibiotic-resistant Enterobacteriaceae and enterococci and the consequences of intestinal outgrowth of these multidrig resistant opportunistic pathogens on pathogen-host cross-talk. Finally, his group performs microbiome-based analysis to decipher the role of the microbiome in health and disease. Dr. Willems has authored more than 200 peer-reviewed papers and book chapters.