DrAnand Shah

Overview
My research is primarily focussed on improving outcome in chronic respiratory infection with a particular focus on bronchiectasis, antimicrobial resistance and pulmonary fungal lung disease (e.g. allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis).

Understanding immune and microbial drivers of exacerbation in bronchiectasis:

I lead a number of academic studies in bronchiectasis including a MRC experimental medicine funded study (BARRIER) to develop a novel human rhinovurus challenge model of bronchiectasis exacerbation which is co-led by Dr Aran Singanayagam and in collaboration with Professor James Chalmers (Oxford) and Professor Sanjay Chotirmal (NTU, Singapore). I lead further prospective cohort studies to study naturally occurring exacerbations in bronchiectais (PRIVILEGE) as well as research bronchoscopy studies (EMILE and THISTLE). Through a number of these studies, our research group at Imperial College London aims to better understand the microbial and immune pathways leading to susceptibility to exacerbation in bronchiectasis and identify potential therapeutic avenues to improve outcome.

Host susceptibility to Aspergillus fumigatus:
During a MRC funded clinical PhD research fellowship in the Armstrong-James laboratory at Imperial College, my research initially focussed on understanding the effects of calcineurin inhibition on the human alveolar macrophage response to Aspergillus fumigatus. I showed that calcineurin inhibition critically impairs the ability of alveolar macrophages to control fungal germination by altering downstream necroptotic pathways and macrophage 'metaforosis', a newly coined actin-dependent human macrophage transfer of conidia to neighbouring cells during programmed cell death, through calcineurin-dependent phosphorylation of the actin polymerase VASP. My research now focusses on wider immune dysreglation and susceptibility to fungal infection within Cystic Fibrosis and non-CF bronchiectasis. We recently published data highlighting the role of type 3 IFN pathways in epithelial response to Aspergillus fumigatus and the effects of novel CFTR modulator therapy in partial correction. We are further actively studying immune pathways critical in ABPA pathophysiology and identifying effects of biologic therapy and novel potential therapeutic targets. 

Antimicrobial resistance:
We have recently shown a rapidly increased global spread of antifungal resistance, particularly affecting individuals with chronic pulmonary fungal disease. The evolution of reistance in this population is as yet unclear. The widespread use of azoles in agriculture is increasing environmental isolate resistance. Long-term azole therapy in these patients can also directly lead to resistance or place selective pressure to enable emergence of resistant infection. In collaboration with Professor Matthew Fisher and Prof Darius Armstrong-James, within a MRC and Wellcome Trust funded study at Imperial College London, I led a multi-centre research collaboration using prospective whole genome sequencing of clinical and environmental Aspergillus isolates to better understand resistance evolution and acquisition.
 

I co-chair the European Respiratory Society Antimicrobial resistance Lung clinical research consortium (AMR-Lung) with over 350 members globally. Through the CRC I lead a number of work packages including the first global registry of AMR in chronic respiratory disease (PRESIDE study) with further longitudinal prospective cohort studies analysing the role of novel molecular diagnostics in understanding evolution of resistance in Pseudomonas aeruginosa and prediction of therapeutic response.