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. 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. 2017; :. doi: 10.1164/rccm.201702-0386OC. PubMed PMID:29095649 .
  2. 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.
  3. 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 .
  4. 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 .
  5. Moodley, S, Derouet, M, Bai, XH, Xu, F, Kapus, A, Yang, BB et al.. Stimulus-dependent dissociation between XB130 and Tks5 scaffold proteins promotes airway epithelial cell migration. Oncotarget. 2016;7 (47):76437-76452. doi: 10.18632/oncotarget.13261. PubMed PMID:27835612 PubMed Central PMC5363521.
  6. Li, CX, Talele, NP, Boo, S, Koehler, A, Knee-Walden, E, Balestrini, JL et al.. MicroRNA-21 preserves the fibrotic mechanical memory of mesenchymal stem cells. Nat Mater. 2017;16 (3):379-389. doi: 10.1038/nmat4780. PubMed PMID:27798620 .
  7. Goldenberg, NM, Steinberg, BE, Rutka, JT, Chen, R, Cabral, V, Rosenblum, ND et al.. Research projects in the Surgeon-Scientist and Clinician-Investigator programs at the University of Toronto (1987-2016): a cohort study. CMAJ Open. ;4 (3):E444-E447. doi: 10.9778/cmajo.20160062. PubMed PMID:27730108 PubMed Central PMC5047840.
  8. Civitarese, RA, Talior-Volodarsky, I, Desjardins, JF, Kabir, G, Switzer, J, Mitchell, M et al.. The α11 integrin mediates fibroblast-extracellular matrix-cardiomyocyte interactions in health and disease. Am. J. Physiol. Heart Circ. Physiol. 2016;311 (1):H96-H106. doi: 10.1152/ajpheart.00918.2015. PubMed PMID:27199132 .
  9. Speight, P, Kofler, M, Szászi, K, Kapus, A. Context-dependent switch in chemo/mechanotransduction via multilevel crosstalk among cytoskeleton-regulated MRTF and TAZ and TGFβ-regulated Smad3. Nat Commun. 2016;7 :11642. doi: 10.1038/ncomms11642. PubMed PMID:27189435 PubMed Central PMC4873981.
  10. Tsang, JL, Jia, SH, Parodo, J, Plant, P, Lodyga, M, Charbonney, E et al.. Tyrosine Phosphorylation of Caspase-8 Abrogates Its Apoptotic Activity and Promotes Activation of c-Src. PLoS ONE. 2016;11 (4):e0153946. doi: 10.1371/journal.pone.0153946. PubMed PMID:27101103 PubMed Central PMC4839753.
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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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