R. L. Williams

Pharmacogenomic synthetic lethal screens reveal hidden vulnerabilities and new therapeutic approaches for treatment of NF1-associated tumors

This study identifies 23 compounds that selectively kill NF1-deficient Schwann cells and shows their efficacy in vivo, with synergy when combined with Selumetinib.

Multifocal, multiphenotypic tumours arising from an MTOR mutation acquired in early embryogenesis

The paper traces the origin of four synchronous renal tumours in a child to an early embryonic MTOR mutation, showing its role in tumour development and clinical implications.

Paradoxical dominant negative activity of an immunodeficiency-associated activating PIK3R1 variant

The paper investigates an activating PIK3R1 variant linked to immunodeficiency and finds it acts as a dominant negative, reducing p110 signaling and explaining overlapping phenotypes.

Molecular basis for differential activation of p101 and p84 complexes of PI3Kγ by Ras and GPCRs

This study identifies molecular differences between p110γ-p84 and p110γ-p101 complexes that explain their differential activation by GPCRs and Ras.

Bipartite binding and partial inhibition links DEPTOR and mTOR in a mutually antagonistic embrace

This study investigates the interaction between DEPTOR and mTORC1, revealing DEPTOR as a partial inhibitor that is more effective against activated mTORC1, with mutual antagonism mediated by phosphorylation and structural interactions.

Metabolic multi-stability and hysteresis in a model aerobe-anaerobe microbiome community

The paper shows that multi-stability and hysteresis explain shifts to and persistence of aerobe-anaerobe microbiome states under changing oxygen and nutrient conditions.