Role of protein misfolding in inflammation and 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 the initiation and progression of chronic lung disorders. We believe that increased understanding of the molecular pathways involved in the response to cellular ER stress and protein misfolding events will enable us to identify novel molecular targets involved in both disease initiation and progression.

Research themes:

• Characterize 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
• Investigate the link between ER stress and chronic inflammation

Recent Papers (2017):

• Ayaub EA, Dubey A, Imani J, Botelho F, Kolb MRJ, Richards CD, Ask K. Overexpression of OSM and IL-6 impacts the polarization of pro-fibrotic macrophages and the development of bleomycin-induced lung fibrosis. Sci. Rep. 2017, Oct 16/7:41598, PMID 2903860
• Yum V, Carlisle R, Lu C, Brimble E, Chahal J, Upagupta C, Ask K, Dickhout JG. Endoplasmic reticulum stress inhibition limits the progression of chronic kidney disease in the Dahl-sensitive rat. Am J Physiol Renal Physiol. 2017 Jan 1;312(1):F230-F244. PMID 28069662
• Mohammed-ali Z, Lu C, Marway M, Carlisle R, Ask K, Lukic D, Krepinsky JC, Dickhout JG. Endoplasmic reticulum stress inhibition attenuates hypertensive chronic kidney disease through reduction in proteinuria. Sci Rep 2017, Feb 2(7):41572, PMID 2814896