Laura's research investigates the roles of Nuclear Receptors in health and disease, with a particular focus on Nuclear Receptor crosstalk in cancer and inflammation.
Nuclear Receptors (NRs) are ligand-regulated transcription factors that are activated by hormones, lipid-soluble factors and metabolites. Upon ligand binding, NRs undergo a conformational switch which changes the protein interaction surface, exposing nuclear localization signals and driving translocation into the nucleus. Once in the nucleus NRs can bind chromatin directly or by tethering to other DNA bound transcription factors, then recruit coactivator or corepressor proteins and chromatin remodelers to activate or inhibit transcription.
NRs are master regulators of development, metabolism, reproduction and immunity. It is therefore not surprising that many diseases including diabetes, obesity, atherosclerosis, airway inflammation, inflammatory bowel disease and most types of cancer have altered NR activity. As NRs are ligand-activated transcription factors, their endogenous ligand provides the perfect template to design high affinity synthetic NR modulators, which makes them tractable drug targets for treating a range of diseases. Indeed, approximately 30% of all new drug leads target NRs.
Laura’s research aims to unravel the complex mechanisms by which NRs mediate their cellular effects, define how changes in NR function drives disease, and also how NR responses are modified by disease processes. Ongoing projects investigate:
- Mechanisms underlying integration of NR signals
- Regulators of tissue specific NR effects
- NR crosstalk in inflammation and cancer
- NR function in healthy ageing
- Therapeutic application of synthetic NR modulators
Using a combination of in vitro, pre-clinical in-vivo models and ex-vivo human tissues Laura’s research aims to transition from 'bench to bedside' to inform new therapeutic approaches to target NRs.