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. Leung, CH, Caldarone, CA, Guan, R, Wen, XY, Ailenberg, M, Kapus, A et al.. Nrf2 Regulates the Hepatoprotective Effects of Remote Ischemic Conditioning in Hemorrhagic Shock. Antioxid. Redox Signal. 2018; :. doi: 10.1089/ars.2018.7541. PubMed PMID:30403148 .
  2. 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. 2018; :fj201800596R. doi: 10.1096/fj.201800596R. PubMed PMID:30148679 .
  3. 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 .
  4. 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. 2018; :. doi: 10.1097/SHK.0000000000001135. PubMed PMID:29489738 .
  5. 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 .
  6. Amoozadeh, Y, Anwer, S, Dan, Q, Venugopal, S, Shi, Y, Branchard, E et al.. Cell confluence regulates claudin-2 expression: possible role for ZO-1 and Rac. Am. J. Physiol., Cell Physiol. 2018;314 (3):C366-C378. doi: 10.1152/ajpcell.00234.2017. PubMed PMID:29187366 .
  7. Zabini, D, Granton, E, Hu, Y, Miranda, MZ, Weichelt, U, Breuils Bonnet, S et al.. Loss of SMAD3 Promotes Vascular Remodeling in Pulmonary Arterial Hypertension via MRTF Disinhibition. Am. J. Respir. Crit. Care Med. 2018;197 (2):244-260. doi: 10.1164/rccm.201702-0386OC. PubMed PMID:29095649 .
  8. Miranda, MZ, Bialik, JF, Speight, P, Dan, Q, Yeung, T, Szászi, K et al.. TGF-β1 regulates the expression and transcriptional activity of TAZ protein via a Smad3-independent, myocardin-related transcription factor-mediated mechanism. J. Biol. Chem. 2017;292 (36):14902-14920. doi: 10.1074/jbc.M117.780502. PubMed PMID:28739802 PubMed Central PMC5592669.
  9. Civitarese, RA, Kapus, A, McCulloch, CA, Connelly, KA. Role of integrins in mediating cardiac fibroblast-cardiomyocyte cross talk: a dynamic relationship in cardiac biology and pathophysiology. Basic Res. Cardiol. 2017;112 (1):6. doi: 10.1007/s00395-016-0598-6. PubMed PMID:28000001 .
  10. Zhang, Y, Connelly, KA, Thai, K, Wu, X, Kapus, A, Kepecs, D et al.. Sirtuin 1 Activation Reduces Transforming Growth Factor-β1-Induced Fibrogenesis and Affords Organ Protection in a Model of Progressive, Experimental Kidney and Associated Cardiac Disease. Am. J. Pathol. 2017;187 (1):80-90. doi: 10.1016/j.ajpath.2016.09.016. PubMed PMID:27993241 .
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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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