Andrew Lewis

Research Project Title: Investigating non-myocyte regulators of mitochondrial health in failing hearts

Research Project Summary: 

Non-myocyte cells are emerging as key regulators of cardiac mitochondrial health, though little is known about the key pathways in disease. Over the course of this BHF CRE Intermediate Clinical Transition Fellowships, I will combine advanced multinuclear magnetic responance spectroscopic techniques (ultra-high field ³¹P and hyperpolarized ¹³C techniques) with single cell and spatial transcriptomics of failing human myocardium to define the role of non-myocytes in the regulation of cardiac mitochondrial structure and function.

The project involves technology development and clinical translation of new non-invasive molecular imaging tools for human cardiac energetic status. We will develop new software tools for acquisition and post-processing of imaging assessments of mitochondrial substrate metabolism as well as high energy phosphorus metabolism to probe human cardiac energetics in unprecedented scope and detail. In addition to roles in studying biological mechanisms of disease, these tools may have future applications for the clinical development of new medicines targeting cardiac mitochondria.

 We have known for almost 30 years that the energetics of failing human hearts are compromised. However, proximate mechanisms responsible for mitochondrial dysfunction in heart failure remain elusive.  The overall aim of this work is to define new targets which could be prosecuted to restore mitochondrial health and energy supply to failing hearts.

Biography:

During my doctoral studies in the Neubauer, Tyler, and Rider groups, I developed new applications for hyperpolarized 13C magnetic resonance (MR) and drove the clinical translation of this technique. The DPhil ignited my interests in collaborative, interdisciplinary cardiovascular science with a clinical focus and my career goal is to become an independent clinician-scientist, leading an innovative and high-performing programme in translational cardiovascular medicine research.

The concept for my programme is to integrate advances in clinical and molecular imaging with discovery biology techniques, in order to study the systems biology of common cardiovascular diseases in humans.

Alongside this growing research programme, I practice clinically as a Cardiologist at the Oxford Heart Centre.