Ask Lab Research
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 occurs 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.
- Characterise ER stress, UPR and upregulation of molecular chaperones in patients with Chronic Lung Disease
- Investigate the role of ER stress and UPR in cigarette smoke induced lung disease
- Investigate the role of ER stress and UPR in pulmonary fibrosis
Peer reviewed manuscripts
- Ask K, Kolb, MRJ. Challenges in Drug Development for Chronic Lung Disease – Mission Impossible? Respirology, 2015 Jan; 20 (1):13-14. PMID: 25470316
- Kolb PS, Ayaub EA, Zhou W, Yum V, Dickhout JG, Ask K. The therapeutic effects of 4-Phenylbutyric acid in maintain proteostasis. International Journal of Bichemistry and Cell Biology. doi: 0.1016/j.biocel.2015.01.015. [Epub ahead of print]. PMID: 25660369 Full text available until April 4 2015
- Mukherjee S, Ayaub E, Murphy J, Kolb M, Ask K, Janssen LJ. Nifedipine Attenuates Bleomycin-Induced Fibrosis By Blocking Calcium Oscillations. American Journal of Respiratory Cell and Molecular Biology. Am J Respir Cell Mol Biol. 2015 February. [Epub ahead of print] PMID: 25664495
- Mohammed-Ali Z, Cruz GL, Lu C, Carlisle RE, Werner KE, Ask K and Dickhout JG. Development of a model of chronic kidney disease (CKD) in the C57BL/6 mouse with properties of progressive human CKD. Biomed Research International Article ID 172302, in press.
- Wei J, Rahman S, Ayaub E, Dickhout JG, Ask K. Protein Misfolding in Chronic Lung Disease. Chest, 2013 Apr 1; 143(4):1098-105. PMID: 23546482
- Wei J, Ayaub E, Bhargava A, Feng Q, Rahman S, Smith JA, Stampfli MR, Ask K: Assessment Of Housekeeping Genes In Inflammatory Mouse Models Of Lung Disease, Am J Resp Crit Care Med, 185:A4163, 2012.
- Wei J, Ayaub E, Morissette MC, Bhargava A, Lynch MH, Smith JA, Inman MD, Austin RC, Stampfli MR, Ask K. FKBP13 deficiency leads to an exacerbated inflammatory response and increased lung compliance following cigarette smoke exposure. Am J Resp Crit Care Med, 187:A2790, 2013.
- Ayaub E, Wei J, Lynch MH, Bhargava A, Yum V, Smith JA, Inman MD, Kolb MRJ, Dickhout JG, Ask K. 4-Phenylbutyrate prevents UPR activation and myofibroblast differentiation in experimental bleomycin-induced lung fibrosis. Am J Resp Crit Care Med, 187:A5657, 2013.
- Ayaub E, Wong N, Wei J, Bhargava A, Smith JA, Lynn E, Austin RC, Inman MD, Dickhout JG, Ask K. Grp78 heterozygosity protects against bleomycin-induced lung fibrosis and inflammation. Am J Resp Crit Care Med, 187:A6125, 2013.
- Department of Medicine
- Firestone Institute for Respiratory Health
- Ontario Thoracic Society- Canadian Lung Association
- Canada Foundation for Innovation
- Ontario Graduate Scholarship