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Sanjay Chotirmall

​​Sanjay Chotirmall-01 (Custom).jpg
 
Assistant Professor Sanjay Haresh Chotirmall
MB BCh BAO (NUI) (Hons), FRCPI, MRCP (UK) (Lond), PhD
Assistant Professor and Provost's Chair in Molecular Medicine
Principal Investigator, Translational Respiratory Research Laboratory

 
​Team

  • ​Louisa Chan, PhD, LKCMedicine Dean's Postdoctoral Fellow and Wong Peng Onn’s Postdoctoral Fellow
  • Fransiskus Xaverius Ivan, PhD, Senior Post-doctoral Research Fellow
  • Tavleen Kaur Jaggi, MBBS, Research Associate
  • Soo Ter Kai, BSc, Research Assistant
  • Tiew Pei Yee, Clinician-Scientist PhD Student 
  • Jayanth Kumar Narayana, PhD Student
  • Valerie Yong Fei Lee, PhD Student 
  • Kenny Lau Jia Xu, PhD student


Introduction

Assistant Professor Sanjay Haresh Chotirmall graduated from the Royal College of Surgeons in Ireland (RCSI) with an honours degree and the colleges’ gold medal in Microbiology. He completed his early clinical training at Beaumont Hospital Dublin, while attaining memberships of the Royal College of Physicians of Ireland (MRCPI) and the United Kingdom (MRCP UK). Following this, he completed higher specialist training in Respiratory and Critical Care Medicine across multiple hospital sites in the Republic of Ireland. 

In 2007, Asst Prof Chotirmall was awarded a prestigious ‘Molecular Medicine Ireland Clinician Scientist Fellowship’ (MMI-CSF). During this fellowship, he completed a PhD investigating the role of estrogen in cystic fibrosis. This work led to high impact publications in the American Journal of Respiratory and Critical Care Medicine (AJRCCM), as well as the New England Journal of Medicine (NEJM). 

Asst Prof Chotirmall has been awarded the Royal Academy of Medicine of Ireland (RAMI) Doctor award on two occasions (2010 & 2013), the Irish Thoracic Society Award (2011), the Dublin Center for Clinical Research (DCCR) Young Investigator Award (2011), the MMI-CSFP Medal (2011), the Royal College of Physicians William Stokes Award for research (2010) and the American Thoracic Societies International Award (2009). Additionally, his work has been recognised by the Faculty of 1000 Biology and Medicine, an online research service that highlights critical papers published in the biological sciences, as recommended by distinguished faculty. In 2018, he was conferred as fellow of the Royal College of Physicians in Ireland (FRCPI) and in 2019 a Fellow of the American College of Chest Physicians (FCCP). In 2020, he was awarded the Alumni Award for ‘Research and Innovation’ by the Royal College of Surgeons in Ireland (RCSI), an accolade reserved for individuals demonstrating exemplary accomplishments and contributions as global healthcare professionals.

Having published numerous peer-reviewed papers, and several book chapters to date, he is regularly invited as chair and speaker at regional, national and international meetings. He remains a member of the International Society of Human and Animal Mycology (ISHAM) working group for fungal infections, a steering committee member for the ATS-led international taskforce on COVID-19 management and participates in various other committees at the American Thoracic Society (ATS) and European Respiratory Society (ERS). He previously served for four consecutive years (2016-2020) on the program committee of the American Thoracic Society (ATS) annual congress for the Assembly on Allergy, Immunology and Inflammation (AII). 

Asst Prof Chotirmall is the Section Editor at the journal BMC Pulmonary Medicine where he leads a team of Associate Editors in the peer review of manuscripts under the ‘Infectious, Rare and Idiopathic Pulmonary Disease’ section. He also takes on editorial roles at the American Journal of Respiratory and Critical Care Medicine (Associate Editor), the European Respiratory Journal (Editorial Board), Respiratory Research (Associate Editor), the American Journal of Physiology-Lung Cellular and Molecular Physiology (Editorial Board), Respirology (Editorial Board), Mycopathologia (Executive Editor) and PLos One (Academic Editor). Asst Prof Chotirmall regularly participates as an investigator for key multi-centre clinical trials in the field of Respiratory Medicine while continuing to educate undergraduates and postgraduates through formal teaching and supervision both at the bench and bedside. He has been appointed by the National University of Ireland (NUI) as the external examiner for the Perdana University-Royal College of Surgeons in Ireland (PU-RCSI) medical programme from 2020-2023. 

As a recognised clinician-scientist, Asst Prof Chotirmall has established a Translational Respiratory Research Group, with focus on infection, inflammation, and immunity, in the context of chronic inflammatory respiratory diseases that affect Asian populations.

 
Research Focus

​​​

Research in the Chotirmall lab shares a core translational respiratory focus with a common goal to improve patient care through advancing the understanding of disease from a scientific basis. The group pursues research in a number of areas with significant clinical importance that impact Singaporeans and other Asian populations;

Chronic inflammatory lung disease
The group investigates the basic mechanisms of clinical relevance in a number of pulmonary conditions including bronchiectasis, chronic obstructive pulmonary disease (COPD) and severe asthma. A major focus is on the investigation of bronchiectasis, a permanent and irreversible dilatation of the airway of high prevalence across Asia. Utilising genomic and molecular approaches combined with high-quality clinical phenotyping, geographic variation in this disease state are elucidated and a personalised approach to clinical manifestations and associated therapeutic responses are explored.

Infectious respiratory disease and the pulmonary microbiome

Central to the lab’s focus is infectious respiratory disease including the pulmonary microbiome. Specifically, how the fungi Aspergillus fumigatus and bacteria Pseudomonas aeruginosa affect major Asian respiratory disease states such as bronchiectasis, COPD and severe asthma are explored. The environmental influence on pulmonary infection in chronic respiratory disease states is also a major interest of the Chotirmall lab.

The investigation of 
Aspergillus-associated pulmonary disease forms a key component of their work. This group of diseases pose clinical, diagnostic and therapeutic challenges in Singapore and the wider South-East Asian region. This is due to the high occurrence of old tuberculosis cavities and the increasing prevalence of structural lung disease such as bronchiectasis. Additionally, allergic manifestations including allergic bronchopulmonary aspergillosis (ABPA) and chronic disease states such as chronic pulmonary aspergillosis (CPA) remain ongoing clinical challenges and are part of the lab’s interests.

T
he study of Pseudomonas focuses primarily on its pathogenesis in bronchiectasis and COPD, and how circulating sex hormones influence virulence, anti-microbial susceptibility, and patient outcomes. High levels of Pseudomonas aeruginosa colonisation is observed in a range of respiratory conditions across Asia and the precise role this bacteria plays in the Asian phenotype’ of lung disease is another goal of Asst Prof Chotirmall and his team's work.

Developing lung organoid model systems for pulmonary disease modelling and the application of precision respiratory medicine

​​


Lung organoids or “lung in a dish” are self-organising three-dimen​sional structures developed from adult stem cells that recapitulate the key structural and functional aspects of the human airways. The Chotirmall lab has established these models for the upper and lower airways using adult stem cells isolated from human nasopharyngeal and bronchial specimens. These well-differentiated and highly functional lung organoid models are characterised by a spheroidal structure which includes several layers of basal cells surrounded by an inner lumen lined by multiple differentiated cell populations including club cells, goblet cells and ciliated cells: all principal components of the human airway. Nasopharangeal organoids (NPOs) and bronchial organoids (BOs) display high physiological similitude of direct applicability to the in vivo lung including mucus swirling and ciliary beating (see video below). Diseased lung organoids have also been established in the lab, modelled for studies of airway remodelling, endophenotyping and the pathogenesis of infection in severe asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis. These represent all the major pulmonary diseases of global significance, which notably occur at high frequency in Asian populations. Such novel model systems can advance the application of precision medicine and discovery science by permitting the study of individualised therapy in a defined state of disease and/or infection. Such models are useful for rapid high throughput therapeutic screening addressing unmet needs in respiratory infection and chronic respiratory disease.​


Selected Publications

Chotirmall SH, Smith SG, Gunaratnam C, et al. (2012). Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis. The New England Journal of Medicine, 366(21):1978-86.

Chotirmall SH, Greene CM, Oglesby IK, et al. (2010). 17β-Estradiol inhibits IL-8 in cystic fibrosis By up-regulating secretory leucoprotease inhibitor. American Journal of Respiratory and Critical Care Medicine, 182(1).

Chotirmall SH, Coughlan CA, Renwick J, et al. (2012). The effect of Aspergillus Fumigatus infection on vitamin D receptor expression in cystic fibrosis. American Journal of Respiratory and Critical Care Medicine, 186(10):999-1007.

​Mac Aogáin M, Chandrasekaran R…Chotirmall SH. (2018). Immunological corollary of the pulmonary mycobiome in bronchiectasis: the CAMEB study. European Respiratory Journal, 52(1), pii 1800766.


Chalmers JD, Chotirmall SH. (2018). Bronchiectasis: new therapies and new perspectives. Lancet Respiratory Medicine, 6(9), 715-726.

Chotirmall SH, Hector A, Lavelle GM, et al. (2016). Chitinase activation in patients with fungus-associated cystic fibrosis lung diseaseJournal of Allergy and Clinical Immunology, 138(4):1183-89.

Chotirmall SH, Martinez FJ, Schumacker PT, Cooke CR, Seam N, Brochard L, Tighe RM, Levy BD, Gern D, Wedzicha JA. 2020. Life at the Editorial "COVID Frontline". The American Thoracic Society Journal Family. Am J Respir Crit Care Med. 15;201(12):1457-1459. doi: 10.1164/rccm.202005-1516ED.

Tiew PY, Ko FWS, Narayana JK, Poh ME, Xu H, Neo HY, Loh LC, Ong CK, Mac Aogáin M, Tan JHY, Kamaruddin NH, Sim GJH, Lapperre TS, Koh MS, Hui DSC, Abisheganaden JA, Tee A, Tsaneva-Atanasova K, Chotirmall SH. 2020. "High-Risk" Clinical and Inflammatory Clusters in COPD of Chinese Descent. Chest. 22:S0012-3692(20)30326-3. doi: 10.1016/j.chest.2020.01.043. Online ahead of print.PMID: 32092320

Mac Aogáin M, Lau KJX, Cai Z, Narayana JK, Purbojati RW, Drautz-Moses DI, Gaultier NE, Jaggi TK, Tiew PY, Ong TH, Koh MS, Hou ALY, Abisheganaden JA, Tsaneva-Atanasova K, Schuster SC, Chotirmall SH. 2020. Metagenomics Reveals a Core Macrolide Resistome Related to Microbiota in Chronic Respiratory Disease. Am J Respir Crit Care Med. doi: 10.1164/rccm.201911-2202OC. Online ahead of print.PMID: 32320621


*Complete list of publications: PubMed


Other Links

  1. Cystic fibrosis breakthrough reveals why females fare worse than males (Science Daily)
  2. Cystic fibrosis breakthrough reveals why females fare worse than males (Health Canal)
  3. Breathing a little easier
  4. Scientist make major cystic fibrosis breakthrough
  5. Irish team make cystic fibrosis discovery​
  6. Royal College of Physicians of Ireland announce winner of 2010 William Stokes Award
  7. Meet the editors at ATS Journals 
  8. COVID-19: Interim Guidance on Management Pending Empirical Evidence. 
    From an American Thoracic Society‐led International Task Force
  9. BMC Pulmonary Medicine Editorial Board​
  10. Singapore’s NTU launches nationwide research initiative to promote lung health​
  11. NTU Singapore Launches Nationwide Lung Health Initiative​
  12. No direct link but climate change could affect response to Covid-19 pandemic: WHO 
  13. NTU probes link between tiny air organisms and respiratory woes​

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