Last year, the PVRI awarded two fellowship grants of £50,000GBP each per annum, to two young and up and coming scientists (with MD or PhD degrees), in the field of pulmonary vascular diseases (PVD). Following a rigorous selection process, Bradley Wertheim and Katharine Clapham were awarded the grants. Below is an update on their progress.
Bradley Wertheim - Brigham and Women's Hospital, Harvard, USA
As a 2017 PVRI Basic Science Fellowship awardee, I study the pathophysiological and pathobiological differences between early and advanced stage pulmonary arterial hypertension (PAH), under the mentorship of Dr Bradley Maron. The overarching objective of this project is to identify treatment targets for PAH patients early in the course of the disease. My project has converging aims:
- Describe the impact of mild elevation in pulmonary artery pressure on right ventricle-pulmonary vascular function and morphology, and
- Identify and validate novel transcriptomic mediators of endothelial dysfunction that are unique to early-stage PAH.
In an abstract that we plan to present at the 2019 PVRI Congress, we show that mild elevation in pulmonary artery pressure is associated with fibrotic remodelling of pulmonary arterioles and RV myocardium, as well as RV-PA uncoupling in the monocrotaline rat model of PAH. We also report a novel method our group developed for isolating high-quality mRNA from rat pulmonary microvascular endothelial cells without tissue culture to explore the biological basis of these observations experimentally. We found that early PAH is associated with a unique endothelial transcriptomic profile, over 2,000 differentially-expressed genes compared to advanced disease. Currently, we are using systems biology to predict novel mediators of early endothelial dysfunction from the transcriptomic data.
The PVRI Basic Science Fellowship provided the support for critical training in advanced haemodynamic analysis and experimental biology. The experience, preliminary data, and publications stemming from this Fellowship will advance my career as a physician-scientist with clinical and scientific expertise in pulmonary vascular disease. In addition, I have also enjoyed learning from other PVRI investigators through scientific collaboration and meetings. I look forward to validating the results of my endothelial transcriptomic analyses at the bench top and presenting our preliminary findings at future PVRI Annual World Congresses.
Bradley Wertheim, MD
Katharine Clapham, Yale, Connecticut, USA
I am very grateful to the PVRI for their funding support of my research project, “Novel Mechanisms of EndoMT in Pulmonary Arterial Hypertension.” Under the guidance of Dr Hyung Chun at Yale University, we have been investigating the role of disrupted BMP and TGFβ signalling components and resultant pulmonary arterial hypertension in a mouse model. I have been further exploring the relevance of this signalling pathway in human disease by investigating the functional significance of rare mutations identified in a cohort of individuals with PAH.
With the start of my postdoctoral training after completion of my clinical cardiology training, I have found it rewarding to now begin investigation of PAH at the bench. It is humbling and fascinating to explore the complex molecular mechanisms that underpin the pulmonary vascular disease I have seen in my patients. After my PVRI Fellowship, I hope to continue research in this area while also caring for patients with pulmonary hypertension.