Imperial College London

Professor Martin Wilkins

Faculty of MedicineNational Heart & Lung Institute

Professor of Clinical Pharmacology
 
 
 
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Contact

 

+44 (0)20 3313 6101m.wilkins Website

 
 
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Assistant

 

Mrs Elizabeth O'Brien +44 (0)20 3313 6101

 
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Location

 

NIHR Imperial Clinical Research FacilityICTEM buildingHammersmith Campus

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Summary

 

Research Summary

  • 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 rare genetic variants (Graf et al Nat Comms 2018) and common genetic variants underlying pulmonary arterial hypertension - PAH - (Rhodes et al Lancet Resp Medicine 2019), unmasked the heterogeneity of PAH from blood transcriptomes profiles (Kariotis et al Nat Comms 2021), a panel of circulating proteins that predict survival in PAH (Rhodes et al Lancet Resp Med 2017; Rhodes et al AJRCCM 2022) and highlight molecular drivers of PAH (Harbour et AJRCCM 2022), the description of the plasma metabolome linked to PAH (Rhodes et al Circulation 2017), and genetic determinants of response to dichloroacetate (Michelakis et al Science Translational Med 2017). 
  • Through an active interest in hypoxia-induced pulmonary hypertension, including the study inhabitants of high altitude environments in the Kyrgyz Republic and Tibet, to better understand genetic factors that confer adaptation, we have identified a key role for the zinc transporter, ZIP12 (Zhao et al Nature 2015). This transporter is upregulated in the remodelled pulmonary vessels in PAH. We have exploited the observation that over activity of ZIP12 contributes to pulmonary vascular remodelling pharmacologically through the generation of a monoclonal antibody that inhibits ZIP12 and this has now entered clinical trials. 
  • Past studies from our lab identified phosphodiesterase type 5 as a therapeutic target for 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). Through BHF funding we have evaluated the effect of iron replacement as a therapeutic strategy for PAH (Howard et al Ann Am Thorac Soc. 2021).