Phillips' research on heme proteins and ligand affinity has provided insights into engineering strategies for physiological functions. He explored the impact of His64 in sperm whale myoglobin on ligand affinity, shedding light on structural changes induced by ligand binding and mechanisms of ligand discrimination in myoglobin. By measuring CO binding properties in various mutants and comparing them to mutant myoglobins, he elucidated how mutations influence CO affinity. In his 1994 study, he delved into how heme proteins like myoglobin and hemoglobin differentiate between oxygen (O2) and carbon monoxide (CO) binding at the atomic level. He investigated the role of nitric oxide in physiological functions by examining the kinetics of NO-induced oxidation in myoglobins and hemoglobins revealing insights into protein engineering strategies aimed at mitigating hypertensive events.