Professor Hughes had a significant leadership role in the establishment of the molecular response criteria and kinase domain mutation screening guidelines that are used world-wide to monitor response and resistance in chronic myeloid leukaemia (CML). He has been a principal investigator on many of the key Global and Australian CML trials that have shaped the way tyrosine-kinase inhibitors (TKI's) are selected and sequenced. He has been a leader in the area of treatment-free remission (TFR) and influential in the recent recommendations to make TFR a mainstream goal of therapy. He has published over 300 papers with over 54,000 citations.

In recognition of his outstanding contributions to the field, Professor Hughes was awarded an L3 Investigator Grant from the NHMRC (2022-2026) for his project "A curative approach for chronic myeloid leukaemia".