The role of ER stress and protein misfolding events in chronic lung disease

Protein misfolding events has over the past 20 years been associated with the pathogenesis of multiple diseases, ranging from diseases of genetic origins (Cystic Fibrosis/1-alpha antitrypsin deficiency) to metabolic disorders (Diabetes) and Cancer.

We are interested to learn more about the molecular events that occur when proteins are not folded correctly in the endoplasmic reticulum (ER) and to elucidate the downstream activation of the Unfolded Protein Response (UPR) to clarify its possible role in disease initiation and progression.

Research Themes

  • Characterise ER stress, UPR and upregulation of molecular chaperones in patients with Chronic Lung Disease
  • Investigate role of ER stress and UPR in cigarette smoke induced lung disease
  • Investigate role of ER stress and UPR in pulmonary fibrosis


Affiliated Organisations

  • Department of Medicine
  • Faculty of Health Sciences
  • Demystifying Medicine Seminar Series
  • Firestone Institute for Respiratory Health (FIRH)
  • St. Joseph's Healthcare Hamilton
  • Research Institute of St. Joe's Hamilton

Funding Support

  • Department of Medicine
  • Firestone Institute for Respiratory Health
  • Ontario Thoracic Society — Canadian Lung Association
  • Canada Foundation for Innovation
  • Ontario Graduate Scholarship

Peer reviewed manuscripts

(2020-Oct) FK506-binding protein 13 expression is upregulated in interstitial lung disease and correlated with clinical severity: a potentially protective role.

  • American Journal of Respiratory Cell and Molecular Biology (In Press)
  • DOI: TBD
  • Tat, V; Ayaub, E; Ayoub, A; Vierhout, M; Naiel, S; Padwal, M; Abed, S; Mekhael, O; Tandon, K; Revill, S; Yousof, T; Bellaye, PS; Kolb, P; Dvorkin-Gheva, A; Naqvi, A; Cutz, J; Hambly, N; Kato, J; Vaughan, M; Moss, J.; Kolb, M; Ask, K

(2020-Oct) Sub-optimal treatment response to anti-IL-5 monoclonal antibodies in severe eosinophilic asthmatics with airway autoimmune phenomena.

  • European Respiratory Journal (In Press)
  • DOI: 10.1183/13993003.00117-2020
  • Mukherjee, M; Forero, D; Tran, S; Boulay, M; Bertrand, M; Bhalla, A; Cherukat, J; Al-Hayyan, H; Ayoub, A; Revill, S; Javkar, T; Radford, K; Kjarsgaard, M; Huang, C; Dvorkin-Gheva, A; Ask, K; Olivenstein, R; Dendukuri, N; Lemiere, C; Boulet, LP; Martin, J; Nair, P

(2020-Oct) Expression of endocannabinoid system components in human airway epithelial cells - Impact of sex and chronic respiratory disease status

  • European Respiratory Journal Open Research (In Press)
  • DOI: 10.1183/23120541.00128-2020
  • Fantauzzi, M; Aguiar, J; Tremblay, B; Mansfield, M; Yanagihara, T; Chandiramohan, A; Revill, S; Ryu,M; Carlsten, C; Ask, K; Stämpfli, M; Doxey, A; Hirota, J

(2020-Sept) Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue.

  • European Respiratory Journal (Published)
  • DOI:10.1183/13993003.01123-2020
  • Aguiar, J; Tremblay, B; Mansfield, M; Woody, O; Lobb, B; Banerjee, Al Chandiramohan, A; Tiessen, N; Cao, Q; Dvorkin-Gheva, A; Revill, S; Miller, M; Caristen, C; Organ, L; Joseph, C; John, A; Hanson, P; Austin, R; McManus, B; Jenkins, G; Mossman, K; Ask, K; Doxey, A; Hirota, J

(2020-Aug) Current models of pulmonary fibrosis for future drug discovery efforts.

  • Expert Opinion on Drug Discovery (Published)
  • DOI: 10.1080/17460441.2020.1755252
  • Yanagihara, T; Chong, SG; Vierhout, M; Hirota, JA; Ask, K; Kolb, M

(2020-June) The importance of interventional timing in the bleomycin model of pulmonary fibrosis.

  • European Respiratory Journal (Published)
  • DOI: 10.1183/13993003.01105-2019
  • Kolb, P; Upagupta, C; Vierhout, M; Ayaub, E; Bellaye, PS; Gauldie, J; Shimbori, C; Inman, M; Ask, K; Kolb, M

(2020-May) Protein misfolding and endoplasmic reticulum stress in chronic lung disease: will cell-specific targeting be the key to the cure? 

  • Chest (Published)
  • DOI: 10.1016/j.ches.2019.11.009
  • Naiel, S; Tat, V; Padwal, M; Vierhout, M; Mekhael, O; Yousof, T; Ayoub, A; Abed, S; Dvorkin-Gheva, A; Ask, K

Abstracts

(2020-May) Characterizing the transcriptomic signature in circulating monocytes and alternatively activated macrophages in idiopathic pulmonary fibrosis 

  • American Thoracic Society
  • A62. Lung Fibrosis: Insights from the bench 
  • Vierhout, M; Mekhael, O; Ayoub, A; Dvorkin-Gheva, A; Hayat, A; Chu, E; Revill, S; Padwal, M ;Cutz, J-C; Naqvi, A; Hirota, JA; Kolb, M; Hambly, N; Ask, K

(2020-May) Characterizing the role of ABCF1 in dsDNA antiviral responses in human airway epithelial cells

  • American Thoracic Society
  • D34. Infections and the immune response
  • Cao, QT; Abbas, N; Aguiar, J; Tremblay, BJ-M; Doxey, A; Revill, S; Ayoub, A; Ask, K, Hirota JA

(2020-May) Intrinsic BMP inhibitor Gremlin regulates lung alveolar stem cell proliferation and differentiation

  • American Thoracic Society
  • D27. Cellular responses informing lung repair
  • Zhou, Q; Yanagihara, T; Revill, S; Chong, SG; Dvorkin-Gheva, A; Ask, K; Kolb, M; Gauldie, J

(2020-May) Anti-inflammatory/anti-fibrotic compound PBI-4425 alleviates bleomycin-and TGF-ß1-Induced pulmonary fibrosis

  • American Thoracic Society
  • A68. Parenchyma/Intersitial lung disease
  • Gagnon, L; Leduc, M; Tremblay, M; Shimbori, C; Sarra-Bournet, F; Felton, A; Yanagihara, T; Ask, K; Kolb, M; Leblond, FA; Grouix, B

(2020-May) The expression and genetic mutation of BMPR2 in the fibrotic lung diseases

  • American Thoracic Society
  • D109. Modulating the Fibrotic Response
  • Yanagihara, T; Ayoub, A; Chong, M; Scallan, CJ; Zhou, Q; Chong, SG; Sato, S; Ask, K; Tikkanen, J; Keshavjee, S; Guillaume, P; Kolb, M

(2020-May) Integrative-Omics identify potential biomarkers and therapeutic targets for idiopathic pulmonary fibrosis

  • American Thoracic Society
  • A62. Lung Fibrosis: Insights from the bench 
  • Yang, CX; Milne, S; Allen, R; Hernandez Cordero, AI; Li, X; Ayoub, A; Ask, K, Hirota, JA, Bossé, Y; Timens, W; Hao, K; Sin, DD; Jenkins, G; Wain, LV; Obeidat, M