McMaster University

Ask Lab

Ask-Lab McMaster Kjetil Ask

Welcome to the Ask Lab

The 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 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 the initiation and progression of chronic lung disorders. We believe that increased understanding of the molecular pathwas 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:

  • 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
  • Investigate the link between ER stress and chronic inflammation

New: A day in the life of the Ask-Lab :-)

This day-in-the-life video serves to demystify aspects of the Ask Lab at McMaster University by following a student's typical day in the lab! The Ask Lab explores protein misfolding events, which have contributed to the development of various diseases such as cystic fibrosis, diabetes, and cancer. This lab is mainly interested in the events in the endoplasmic reticulum (ER) which occur when proteins do not fold correctly. The Unfolded Protein Response (UPR) is discussed, which may play a role in the development and further progression of chronic lung diseases. In addition, the video covers what fibrosis is and how we can test that in the lab, as well as the clinical implications. This video features a talk from a PhD student Ehab Ayaub, a Masters candidate Sohail Mahmood, and principal investigator Dr. Kjetil Ask.

This video was created by Health Science 4DM3 students: Mawleshan Pathmajarah, Hassan Alsaleh, Dana Abu-Jazar, Aunima Bhuiya, and Hina Abdulla. Please let us know waht you think about this video here.


Recent Papers: 2016

 

Ayaub EA, Kolb PS, Mohammed-ali Z, Tat V, Murphy J, Bellaye PS, Shimbori C, Boivin FJ, Lai R, Lynn EG, Lhotak S, Bridgewater D, Kolb MRJ, Inman MD, Dickhout JG, Austin RC and Ask K. GRP78 and CHOP modulate macrophage apoptosis and the development of bleomycin-induced pulmonary fibrosis. Journal of Pathology. http://www.ncbi.nlm.nih.gov/pubmed/27135434

  • Janssen LJ, Mukherjee S, Ask K. Calcium-signalling and ionic mechanisms in human pulmonary fibroblasts. Am J Respir Cell Mol Biol. 2015 Mar 18. [Epub ahead of print] PMID: 25785898.
  • 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.