SPOTLIGHT ON DR NICK MORELL
Affiliations:
BHF Professor of Cardiopulmonary Medicine
Director, Cambridge Heart and Lung Research Institute
Research focus:
Genomics, disease modelling, cell and molecular biology of the rare disease, pulmonary arterial hypertension (PAH); translational and experimental medicine in PAH; Transforming growth factor-b and bone morphogenetic protein function in vascular disease and endothelial biology.
Recent advance from the lab:
We created an MRC/BHF-funded cohort of 800 patients with PAH with detailed longitudinal clinical data, and initiated an international Consortium for Genetics in PAH. These cohorts are delivering novel insights into disease biology and revealing new therapeutic targets and biomarkers employing a highly collaborative multi-omics approach.
Nick Morell
- Swietlik, Greene, Zhu et al. Circ Genom Precis Med (2020)
- Zhu, Swietlik, Welch et al. Genome Med (2021)
- Kariotis, Jammeh, Swietlik et al. Nat Commun (2021)
- Rhodes, Christopher et al. Am J Respir Crit Care Med(2022)
Key challenge for the field:
Around 70% of patients with PAH still do not have a genetic diagnosis based on existing approaches. We are now interrogating the entire genomes of our cohorts to begin to identify the missing heritability in PAH, although the tools to do this are still in a state of evolution. Recognising that environmental and other factors are playing a role in PAH is a major challenge, further complicated by reduced gene penetrance in this condition. This is now being addressed through the longitudinal follow up of unaffected mutation carriers to try to identify the non-genetic triggers of disease.
Most exciting basic or clinical breakthrough in the past few years:
The major genetic cause of PAH was discovered over 20 years ago and only now are we seeing new therapeutic approaches targeting this pathway moving into clinical trials. The results are already looking promising and it will be exciting to see how these approaches impact on the mortality and morbidity of PAH.
Published February 2022