Harriet Keane

Harnessing advances in science and technology can deliver transformative therapies faster while reducing the socioeconomic burden of disease.

At the dawn of a new decade, we take stock of advances and unmet needs in the oncology pharmaceutical market. What will it take to deliver innovation to patients over the next ten years?

Five key trends are driving growth in oncology. To be successful in oncology, a focus on capabilities is critical—both the ones in place today and the ones needed to stay competitive.

Innovations in biomedical sciences and technology fuel the opportunity to transform R&D for new-drug development holistically—500 days faster, better tailored to patient needs, and 25 percent cheaper.

As innovation reshapes the pharma landscape, pharma companies will need to revisit their R&D operating models to thrive.

Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson's disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic… Show more

Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson's disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases. Show less

The cyclisation of alkynyl amido- and amino-malonates in the presence of manganese(III) acetate gives exo-alkylidene pyrrolidinones and pyrrolidines with a preference for the (Z)-alkene product isomer.