- Our research is focused on pulmonary hypertension and is patient orientated. We have established a cohort of patients with clinical data and an associated tissue bank for biomarker studies. We have used this in national and international studies to identify genetic risk factors for pulmonary hypertension and accessible biomarkers that inform prognosis and response to treatment. Among our recent successes are the identification of common genetic variants (Rhodes et al Lancet Resp Medicine 2019), a panel of circulating proteins that predict survival (Rhodes et al Lancet Resp Med 2017), the description of the plasma metabolome linked to pulmonary arterial hypertension (Rhodes et al Circulation 2017) and genetic determinants of response to dichloroacetate (Michelakis et al Science Translational Med 2017).
- We have an active interest in hypoxia-induced pulmonary hypertension. We reported that the zinc transporter, ZIP12, has a critical role in the pulmonary vascular response to hypoxia and is upregulated in the remodelled pulmonary vessels in other presentations of pulmonary arterial hypertension (Zhao et al Nature 2015). We study inhabitants of high altitude environments, in the Kyrgyz Republic and Tibet, to better understand genetic factors that confer adaptation; the hypothesis is that these will signpost molecular pathways that can be exploited pharmacologically.
- Past studies from our lab identified phosphodiesterase type 5 as a therapeutic target for pulmonary arterial hypertension (PAH) using cell and animal models and clinical trials (Zhao et al Circulation 2001; Sebkhi et al Circulation 2003; Wilkins et al AJRCCM 2005; Francis et al ERJ 2010). The phosphodiesterase type 5 inhibitor, sildenafil, was approved for the treatment of PAH by the FDA in May 2005.
- Our studies have demonstrated that iron deficiency in PAH is associated with poor survival (Rhodes et al JACC 2011). We have a BHF funded programme grant to investigate iron replacement in PAH, using haemodynamics and exercise testing as outcome measures (Howard et al Pulm Circ 2012). We expect to publish the results of our clinical study in 2019.