Drug Discovery & Delivery

Overview

There is a continued need to grow the pipeline of new therapies for cardiovascular disease, to provide paired diagnostics for rational stratification, and to accelerate the translation of these discoveries into new treatments. The vision for the BHF Oxford CRE’s Drug Discovery & Delivery theme is to integrate emerging new targets, mechanistically informative biomarkers with state-of-the-art physical science technologies in probe and drug development, imaging modalities and drug delivery capabilities.

Using large scale patient datasets and single-cell multi-omics from human tissue, we will triage new therapeutics targets. This theme, together with the integrated sub-themes, will deliver:

i) A deeper molecular-level understanding of disease biology
ii) Specific and sensitive disease biomarkers, and companion diagnostic technologies 
iii) New probe and drug candidate identification
iv) State-of-the-art drug delivery technologies.

Sub-themes reflect our established and emerging world leading expertise and methodologies (Enabling Technologies), and emerging areas for new therapeutic discoveries (Metabolic Signalling and Immunomodulation & Memory). Through open-innovation science, industry partnerships and spinouts, this theme will innovate next generation therapies for CVD.

Sub-Theme 1: Enabling Technologies (Lead: Stevens)

We have pioneered a close integration between physical sciences and cardiovascular science through our previous CREs. Under this sub-theme we will build on this, particularly through the Human Models Systems sub-theme of the Repair and Regeneration [LINK] theme. Our research areas include catalysing the application of cutting edge ultra-high resolution analytical methods to bring new capabilities cardiovascular and metabolic disease biology, building on foundational nanoscience technologies for new biomarker and diagnostic discovery, development of new chemical probes and drug candidates, and new drug delivery technologies.

Sub-theme 2: Metabolic signalling (Lead: Hodson)

Metabolic signalling sits at the interface between metabolic regulators and cellular processes. Changes in signalling can impact on inter-organ crosstalk and dysregulation is linked to increased risk of cardiometabolic diseases (e.g. type 2 diabetes (T2D), metabolic dysfunction- associated steatotic liver disease (MASLD) and CVD); all are associated with obesity. This sub-theme builds on and aims to integrate work from investigators focussing on mechanisms linking adipose tissue (AT) with hepatic and cardiovascular disease. 

Sub-theme 3: Immunomodulation and memory (Lead: Choudhury)

The overarching concept for this sub-theme derives from an appreciation that cells that have been associated with “immune” function are in fact responsible for broad aspects of tissue homeostasis. By extension, disruption of these homeostatic functions can lead to disease processes that are relevant to the cardiovascular system [and beyond]. This homeostatic regulation is subject to influence from a number of metabolic cues such as glucose, hyperlipidemia, pH, and lactic acid, that are directly relevant to cardiac disease and risk. These immunometabolic influences exist in addition to, and alongside, more conventional immunologic cues (chemokines; cytokines; DAMPs; PAMPs).  This sub-theme cultivates the work of investigators configured around relevant clinical challenges and opportunities and enabled by access to state-of-the-art technologies, new models and international collaboration.