College of Medicine

Research Area(s)

  • Pulmonary inflammation & inflammasome assembly
  • Hyperinflammatory pulmonary diseases
  • Cystic fibrosis
  • Molecular biophysics
  • Quantitative analyses
  • Cell biology
  • Cell signaling

We're Recruiting!

Looking for a graduate student to study the molecular origins of pulmonary inflammation in primary human airway cells. Please send me an email with a CV.

About

Assistant Professor, Anatomy, Physiology & Pharmacology, University of Saskatchewan.

Ph.D. in Quantitative Molecular Biophysics, Department of Physics & Astronomy, McMaster University.

M.Sc. in Material Sciences, Department of Materials and Interfaces, Weizmann Institute of Science

B.Sc. Honors Physics & Mathematics, Bethlehem University

Research Interests

Hyperinflammatory pulmonary diseases, such as COPD, are potentially fatal, and negatively impact affected individuals and the Canadian health care system. Fatalities due to these diseases ranked 5th since 2016 in Canada. Affected individuals suffer dysregulation in pulmonary inflammation, which is a vital defense mechanism against invading pathogens and danger signals. Understanding the molecular factors responsible for inflammation regulation is very importance in order to advance the molecular understanding of disease development in Canada, evaluate new therapies based on newly defined molecular standards in health and disease, and ultimately identify molecular targets to suppress the progression of disease. This is all to alleviate the suffering of Canadians and reduce the burden on our health care system.

At the molecular level, pulmonary inflammation is regulated by the innate immune system through the assembly of an active inflammasome in immune cells. The Inflammasome is a cytoplasmic macromolecular complex of various proteins which following assembly triggers the release of proinflammatory cytokines such as IL-1 and IL-18. Some of the constituents of the NLRP3 inflammasome, the most characterized inflammasome that is assembled in response to a variety of pathogenic and sterile signals, were detected in human airway epithelial cells, which form the earliest line of defense in the face of danger. The molecular origins of inflammation regulation are not yet well-understood in airway epithelial cells, which are valuable therapeutic targets for the discovery and the development of new drugs.

To fully understand the molecular basis of inflammation progression in hyperinflammatory pulmonary diseases, my lab is focused on studying the spatio-temporal assembly of the NLRP3 inflammasome in human airway epithelial cells under different inflammatory conditions to decipher the factors responsible for its assembly, activation and finally its resolution. This work will be done in live human airway epithelial cells derived from the lungs of healthy donors and those suffering from hyperinflammatory pulmonary diseases such as COPD and cystic fibrosis (CF). A combination of high-quality fluorescence confocal imaging and image-based quantitative molecular biophysics analyses will be the main methodologies used in my lab.

Some of the important quantitative methods used are fluorescence correlation spectroscopy (FCS) technique and its image-based derivative; the k-space image correlation spectroscopy (kICS) analysis. These techniques non-invasively measure a wide range of molecular mobilities, aggregation states and interactions of proteins of interest intracellularly and at the plasma membrane.

Publications

Abu-Arish A., Pandzic E., Luo Y., Sato Y., Turner M., Wiseman P. W. & Hanrahan J. W. (2021) Lipid-driven CFTR clustering is impaired in CF and restored by corrector drugs. JCS #JOCES/2021/259002

Kim D., Liao J., Scales N. B., Martini C., Luan X. J., Abu-Arish A., Robert R., Luo Y., McKay G. A., Nguyen D., Twefik M. A., Poirier C. D., Matouk E., Ianowski J., Frenkiel S. & Hanrahan J. W. (2021) Large pH oscillations promote host defense against human airways infection. JEM. 218 (4): e20201831

Abu-Arish A., Pandzic E., Kim D., Wiseman P. W. & Hanrahan J. W. (2019) Agonists that Stimulate Secretion Promote the Recruitment of CFTR into Membrane Lipid Microdomains. J Gen Physiol. 151 (6): 834-49

Selected for a Research News Article: Sedwick C. (2019) CFTR gets together. JGP. 151 (6): 705.

Kim D., Huang J., Billet A., Abu-Arish A., Goepp J., Matthes E., Tewfik M. A., Frenkiel S. & Hanrahan J. W. (2019) Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia. Am J Respir Cell Mol Biol. 60 (6): 705-16

Highlighted in a “Red alert” by AJRCMB. Nguyen JP & Hirota JA (2019) Ion the prize: defining the complexities of airway epithelial cell ion transport functions. AJRCMB. 60 (6): 618-20

Pandzic E., Abu-Arish A., Whan R. M., Hanrahan J. W. & Wiseman P. W. (2018). Velocity Landscape Correlation Resolves Multiple Flowing Protein Populations From Fluorescence Image Time Series. Methods. 140-141: 126-39

Huang J., Kim D., Shan J., Abu-Arish A., Luo Y. & Hanrahan J. W. (2018) Most Bicarbonate Secretion by Calu-3 Cells is Mediated by CFTR and Independent of Pendrin. Physiol Rep. 6 (5): e13641

Wong F. H., AbuArish A., Matthes E., Turner M. J., Greene L. E., Cloutier A., Robert R., Thomas D. Y., Cosa G., Cantin A. M. & Hanrahan J. W. (2018) Cigarette Smoke Activates CFTR through ROS-Stimulated cAMP Signaling in Human Bronchial Epithelial Cells. Am J Physiol Cell Physiol. 314 (1): C118-C134

Garic D., De Sanctis J. B., Wojewodka G., Houle D., Cupri S., Abu-Arish A., Hanrahan J. W., Hajduch M., Matouk E. & Radzioch D. (2017) Fenretinitde Differentially Modulates the Levels of long- and Very Long-Chain Ceramides by Downregulating Cers5 Enzyme: Evidence from Bench to Bedside. J. Mol. Med (Berl). 95 (10): 11053-64

Klein H., Abu-Arish A., Trinh N. T. N., Luo Y., Wiseman P. W., Hanrahan J. W., Brochiero E. & Sauve R. (2016) Investigating CFTR and KCa3.1 Protein/Protein Interactions. PLoS ONE 11 (4): e0153665.

Abu-Arish A., Pandzic E., Goepp J., Matthes E., Hanrahan J. W. & Wiseman P. W. (2015) Cholesterol Modulates CFTR Confinement in the Plasma Membrane of Primary Epithelial Cells. Biophys. J. 109 (1): 85-94.

Recognized as New and Notable: Clayton A.H.A & Chattopadhyay A. (2015) Get your kICS by Measuring Membrane Protein Dynamics. Biophys. J. 109 (1): 1-2.

Abu-Arish A., Porcher A., Czerwonka A., Dostatni N. & Fradin C. (2010) High Mobility of Bicoid Captured by Fluorescence Correlation Spectroscopy: Implication for the Rapid Establishment of Its Gradient. Biophys. J. 99 (4): L33-35.

Porcher A., Abu-Arish A., Huart S., Roelens B., Fradin C. & Dostatni N. (2010) The Time to Measure Positional Information: Maternal Hunchback is Required for the Synchrony of the Bicoid Transcriptional Response at the Onset of Zygotic Transcripton. Development. 137 (16): 2795-2804.

Abu-Arish A., Kalab P., Ng-Kamstra J., Weis K. & Fradin C. (2008) Spatial Distribution and Mobility of the Ran GTPase in Live Interphase Cells. Biophys. J. 97 (8): 2164-2178.

Wong F. H. C., Bank D. S., Abu-Arish A. & Fradin C. (2007) A Molecular Thermometer Based on Fluorescent Protein Blinking. JACS. 129 (34): 10302-10303.

Highlighted in Nature 448: 842.  Featured in NewScientist 195:30.

Salman H., Abu-Arish A., Oliel S., Loyter A., Klafter J., Granek R. & Elbaum M. (2005) Nuclear Localization Signal Peptides Induce Molecular Delivery along Microtubules. Biophys. J. 89: 2134-2145.

Abu-Arish A., Frenkiel-Krispin D., Fricke T., Tzfira T., Citovsky V., Grayer Wolf S. & Elbaum M. (2004) Three-dimensional Reconstruction of Agrobacterium VirE2 Protein with Single-stranded DNA. J. Biol. Chem. 279: 25359-25363.

Fradin C., Abu-Arish A., Granek R. & Elbaum M. (2003) Fluorescence Correlation Spectroscopy close to a Fluctuating Membrane. Biophys J. 84(3):2005-20.