LABORATORY OF MOLECULAR MEMBRANE BIOLOGY

Head: Katarzyna Kwiatkowka

 

Degrees:

2012 Professor of Biological Sciences, nomination by the President of the Republic of Poland, Nencki Institute of Experimental Biology, PAS

2003 DSc Habl, Nencki Institute of Experimental Biology, PAS

1993 PhD in Biology, Nencki Institute of Experimental Biology, PAS

1986 MSc in Biology, Nicolaus Copernicus University in Toruń

 

Research trainings:

1993-1995 Postdoctoral fellowship, University of Texas Southwestern Medical Center, Dallas, USA

 

Professional employments:

2013-present Head of the Laboratory of Molecular Membrane Biology, Nencki Institute of Experimental Biology PAS, Warsaw

2006-2012 Associate professor, Nencki Institute of Experimental Biology PAS

2006-present Head of the Department of Cell Biology, Nencki Institute of Experimental Biology PAS, Warsaw

1993-2006 Adjunct professor, Nencki Institute of Experimental Biology PAS, Warsaw

1992-1993 Assistant scientist in the Laboratory of Cytochemistry, Nencki Institute of Experimental Biology PAS

 

Honors and fellowships:

2001, 2004, 2011 Prizes of the Second Division of the Polish Academy of Sciences for the team of the Laboratory of Plasma Membrane Receptors

Staff: Anna Ciesielska, Justyna Dembińska (PhD student), Aneta Hromada-Judycka, Orest Matveichuk (PhD student), Andrzej Sobota (Professor emeritus), Gabriela Traczyk, Kamila Prymas (PhD student), Ewelina Ziemlińska

Research profile:


Our studies concern the molecular mechanisms of activation of receptors localized in the plasma membrane of immune cells with a focus on signal transduction by TLR4 which serves as a signaling receptor for bacterial lipopolysaccharide (LPS). Activated TLR4 triggers downstream pathways leading to production of pro-inflammatory mediators which can evoke a septic shock. TLR4 is assisted by CD14 protein anchored in the plasma membrane nanodomains (rafts) enriched in distinct lipids and contribution of those lipids to LPS-inducing signaling is in the center of our studies. We are especially interested in the role of the turnover of PI(4,5)P2, ceramide and acylated proteins in LPS-stimulated macrophages. Our aim is to elucidate how signaling complexes of TLR4 are assembled in the plasma membrane, how they interact with the actin cytoskeleton, and how microdomain organization of the plasma membrane affects formation of those complexes and subsequent endocytosis of the receptor. We conduct the studies on cell culture lines, CD14 knockout mice and primary macrophages transiently or stably depleted/overex- pressing distinct proteins of LPS-induced signaling pathways. For analyses we utilize an array of molecular biology and immunobiology techniques, and also immunoelectron and confocal microscopy, various biochemical techniques including “click chemistry” and mass spectrometry. These complementary approaches are dedicated to unravel factors shaping the mode and magnitude of activation of macrophages by LPS and can in the future help to invent new therapeutic tools for the treatment of sepsis.



Current research activities:

 

  • elucidating the role of plasma membrane lipid, PI(4,5)P2, in LPS-induced production of pro-inflammatory mediators and cell migration. We aim to dissect the contribution of CD14 and TLR4 to signaling pathways which controls phosphatidylinositol turnover in LPS-stimulated cells, identify enzymes involved in PI(4,5)P2 generation and depletion in these conditions and reveal effectors of the lipid shaping the response of macrophages to LPS.
  • exploring the role of S-acylation (palmitoylation) of proteins in signaling activity of TLR4. These studies include proteomics analysis of changes of S-acylation of proteins based on metabolic labeling of macrophages with palmitic acid analogue, “click chemistry” and application of mass spectrometry to identify labeled proteins. The goal of these studies is to establish whether modification of proteins with palmitic acid, a typical component of the westernized diet, can affect pro-inflammatory signaling triggered by LPS.
  • examining  how  activation  of  macrophages  by  LPS depends on the participation of raft lipids, sphingomyelin and ceramide, and raft proteins, including CD14 and tyrosine kinase Lyn, and how this activation is modulated by naturally occurring exogenous lipids, like bis(monoacylglycerol)phosphate. Studies include microscopic and biochemical analysis of an assembly of TLR4 signaling complex and immune responses of macrophages depleted or enriched in distinct raft proteins and lipids.



Selected publications:

 

Płóciennikowska A., Hromada-Judycka A., Dembińska J., Roszczenko P., Ciesielska A., Kwiatkowska K. (2016) Contribution of CD14 and TLR4 to changes of PI(4,5)P2 level in LPS-stimulated cells. J Leukoc Biol, 100: 363-1373.

 

Ciesielska A., Sas-Nowosielska H., Kwiatkowska K. (2016) Bis (monoacylglycerol) phosphate inhibits TLR4-dependent RANTES production in macrophages. Int J Biochem Cell Bio, 83: 15-26.

 

Płóciennikowska A., Zdioruk M.I., Traczyk G., Świątkowska A., Kwiatkowska K. (2015) LPS-induced clustering of CD14 triggers generation of PI(4,5)P2. J Cell Sci, 128: 4096-4111.

 

Kwiatkowska K., Marszałek-Sadowska E., Traczyk G., Koprowski P., Musielak M., Ługowska A., Kulma M., Grzelczyk A., Sobota A. (2014) Visualization of cholesterol deposits in lysosomes of Niemann-Pick type C fibroblasts using recombinant perfringolysin O. Orphanet J Rare Dis, 9: 64.

 

Borzęcka K., Płóciennikowska A., Björkelund H., Sobota A., Kwiatkowska K. (2013) CD14 mediates binding of high doses of LPS but is dispensable for TNF-α production. Mediators Inflamm, 2013: 824919.