Paula Leandro research interests have been centred on the study of the Biochemical and Molecular Basis of Inherited Metabolic Disorders (IMD). During her PhD she focused on the study of phenylketonuria (PKU). Her work led to the identification of the mutational spectrum of the Portuguese PKU population and to the development of expression systems to produce and characterize the associated variant proteins. In this field she extended her scientific interests to the study of the mechanisms underlying negative interallelic complementation, observed in compound heterozygous patients, having demonstrated the assembly of hybrid proteins with functional/structural properties deviating from their homomeric counterparts. The experience acquired in the area of protein characterization allowed expanding these studies to other IMD, namely to deficiencies in cystathionine β-synthase, galactose-1-phosphate-uridyl-transferase, pyruvate dehydrogenase and medium-chain acyl-CoA dehydrogenase. As for the majority of IMDs, dietetic approaches are the main available treatments, in recent years she has been using biochemical and biophysical tools to study the effect of small molecules on the rescue of enzyme activity/conformation in order to develop pharmacological therapies. In addition, aiming the development of enzyme replacement therapies she has been interested in optimizing formulation conditions that promote enzyme stabilization with maintenance of protein activity/structure (biopharmaceutical development). The acquired skills in the area of “Protein Biochemistry”, and particularly in the field of protein functional/structural characterization, led to the establishment of several collaborations aiming protein characterization and biopharmaceutical development in areas beyond the scope of IMDs.