Andras Kapus

MD, PhD

Platform Director, Keenan Research Centre for Biomedical Science

Biography

My lab has two major research foci:

1. The biology of epithelial-mesenchymal transition (EMT), a key process underlying tissue fibrosis. Our goal is to understand how normal epithelial cells (particularly of the kidney) transform into matrix-producing (scar-forming) invasive and contractile myofibroblasts. Our major interest is to explore the cellular and molecular mechanisms whereby injury of the intercellular contacts leads to EMT. This basic research allows insight into fundamental mechanisms responsible for the pathogenesis of major disease entities such as kidney and lung fibrosis and liver cirrhosis.

2. Signaling in osmotic stress and cell volume regulation. Normal volume and water content is vital for every cell. We investigate how dehydration and the corresponding cell shrinkage initiate adaptive responses that include reinforcement of the cell structure (cytoskeleton), remodeling of organelles, activation of ion transport processes and osmosensitive genes. We examine how volume-dependent signaling results in adaptation and survival or, in severe cases, a programmed cell death. This basic research helps elucidate how cells cope with stress conditions, which occur in a variety of disease states, including diabetes, dehydration, trauma and heart failure.

Recent Publications

  1. Yeung, T, Fung, O, Bashkurov, M, Khandani, A, Subedar, O, Wudwud, A et al.. Avoidance of apoptotic death via a hyperploid salvage survival pathway after platinum treatment in high grade serous carcinoma cell line models. Oncotarget. 2019;10 (62):6691-6712. doi: 10.18632/oncotarget.27330. PubMed PMID:31803363 PubMed Central PMC6877103.
  2. Dan, Q, Shi, Y, Rabani, R, Venugopal, S, Xiao, J, Anwer, S et al.. Claudin-2 suppresses GEF-H1, RHOA, and MRTF, thereby impacting proliferation and profibrotic phenotype of tubular cells. J Biol Chem. 2019;294 (42):15446-15465. doi: 10.1074/jbc.RA118.006484. PubMed PMID:31481470 PubMed Central PMC6802501.
  3. Demian, WL, Persaud, A, Jiang, C, Coyaud, É, Liu, S, Kapus, A et al.. The Ion Transporter NKCC1 Links Cell Volume to Cell Mass Regulation by Suppressing mTORC1. Cell Rep. 2019;27 (6):1886-1896.e6. doi: 10.1016/j.celrep.2019.04.034. PubMed PMID:31067471 .
  4. Bialik, JF, Ding, M, Speight, P, Dan, Q, Miranda, MZ, Di Ciano-Oliveira, C et al.. Profibrotic epithelial phenotype: a central role for MRTF and TAZ. Sci Rep. 2019;9 (1):4323. doi: 10.1038/s41598-019-40764-7. PubMed PMID:30867502 PubMed Central PMC6416270.
  5. Kofler, M, Speight, P, Little, D, Di Ciano-Oliveira, C, Szászi, K, Kapus, A et al.. Mediated nuclear import and export of TAZ and the underlying molecular requirements. Nat Commun. 2018;9 (1):4966. doi: 10.1038/s41467-018-07450-0. PubMed PMID:30470756 PubMed Central PMC6251892.
  6. Leung, CH, Caldarone, CA, Guan, R, Wen, XY, Ailenberg, M, Kapus, A et al.. Nuclear Factor (Erythroid-Derived 2)-Like 2 Regulates the Hepatoprotective Effects of Remote Ischemic Conditioning in Hemorrhagic Shock. Antioxid Redox Signal. 2019;30 (14):1760-1773. doi: 10.1089/ars.2018.7541. PubMed PMID:30403148 .
  7. Lichner, Z, Saleeb, R, Butz, H, Ding, Q, Nofech-Mozes, R, Riad, S et al.. Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance. FASEB J. 2019;33 (1):1347-1359. doi: 10.1096/fj.201800596R. PubMed PMID:30148679 .
  8. Chen, Z, Kapus, A, Khatri, I, Kos, O, Zhu, F, Gorczynski, RM et al.. Cell membrane-bound CD200 signals both via an extracellular domain and following nuclear translocation of a cytoplasmic fragment. Leuk Res. 2018;69 :72-80. doi: 10.1016/j.leukres.2018.04.007. PubMed PMID:29698858 .
  9. Safavian, D, Leung, CH, Kapus, A, Ailenberg, M, Szaszi, K, Shani, R et al.. Hemorrhagic Shock/Resuscitation Reduces the M2 Phenotype of Alveolar Macrophages: A Potential Mechanism Contributing to Increased LPS-Induced Lung Injury. Shock. 2019;51 (2):213-220. doi: 10.1097/SHK.0000000000001135. PubMed PMID:29489738 .
  10. Filewod, NC, Batt, J, Kapus, A, Szaszi, K, Fairn, GD, Slutsky, AS et al.. Should basic science matter to clinicians?. Lancet. 2018;391 (10119):410-412. doi: 10.1016/S0140-6736(18)30199-5. PubMed PMID:29407017 .
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Affiliations & Other Activities

  • Scientist, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital
  • Member of the Basic Science Committee, Li Ka Shing Knowledge Institute, St. Michael’s Hospital
  • Associate Vice Chair of Research, Department of Surgery, University of Toronto
  • Former grant review panel member, Kidney Foundation of Canada
  • Member, Banting Foundation Grant Panel
  • Member of the research committee, Department of Surgery
  • Regular Member, Institute of Medical Science (IMS), University of Toronto
  • Member of the Appointments Committee, Institute of Medical Science (IMS), University of Toronto
  • Course Coordinator: Cell Migration Course, Human Biology Program
  • Seminar leader (biochemistry for medical students)
  • Reviewer at several international journals including Amer. J. Physiol., Amer. J. Pathol., Amer. J. of Respiratory Cell and Mol. Biol., Biochem. J., J. Cell Science, EMBO J, Exp. Cell Research, FEBS letters, J. Biol. Chem., J. Leukocyte Biol., Oncogene, PNAS, Thrombosis and Hemostasis and others
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