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  • Laboratory of Molecular and Cellular Neurobiology: Jaworski Laboratory

Laboratory of Molecular and Cellular Neurobiology: Jaworski Laboratory

Jacek Jaworski, PhD, Professor

Correspondence address:
Laboratory of Molecular and Cellular Neurobiology
International Institute of Molecular and Cell Biology
4 Ks. Trojdena Street, 02-109 Warsaw, Poland
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
tel: +48 (22) 597 0755; fax: +48 (22) 597 0715

Degrees:
2014 Professor of Biological Sciences, nomination by the President of the Republic of Poland
2010 DSc Habil in Molecular Biology, Warsaw University, Poland
2001 PhD in Molecular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
1996 MSc in Biology, Department of Genetics, Warsaw University, Poland

Research Training:
2011 Research visit with Dr. C. Sala, Instituto Carlo Besta, Milan, Italy2006 Research visit with Dr. C.C. Hoogenraad, Erasmus Medical Center, Rotterdam, Holland
2002-2005 Postdoctoral Associate with Prof. Morgan Sheng, Picower Center for Learning and Memory, Massachusetts Institute of Technology and Howard Hughes Medical Institute, Cambridge, MA, USA
2000 Research training with Dr. J. Guzowski, ARL Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, USA
1997-2001 Research training (7 months) with Prof. J. Mallet, Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus Neurodegeneratifs (LGN), UMR 9923 CNRS, Paris, France
1996-2002 PhD student (until 2001) and Postdoctoral Associate (until May 2002) with Prof. L. Kaczmarek, Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
1995-1996 Master’s degree, Prof. P. Węgleński, Department of Genetics, Warsaw University, Poland

Fellowships and awards:
2011 Prime Minister Award for habilitation thesis
2009 2nd Division (Biological Sciences) of Polish Academy of Sciences Award for series of publications on MMP9 (together with teams of Prof. Kaczmarek and Dr. Wilczynski)
2005 Konorski Award for best publication of 2004 in the field of neuroscience (Kowalczyk et al., JCB, 2004, 167:209-213), Polish Neuroscience Society and Polish Academy of Sciences
2002 Prime Minister Award for PhD thesis
2001 Foundation for Polish Science National Scholarship for Young Investigators (1 year scholarship)
2000 EMBO Short Term Fellowship
1999 Polish Network for Cell and Molecular Biology UNESCO/PAN Scholarship
1997 Bourse de Stage du Gouvernement Francaise (French Government Scholarship)


Description of Current Research

Mammalian/mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that is involved in almost every aspect of mammalian cell function. It forms two protein complexes, initially identified as regulating translation (mTORC1) or influencing the actin cytoskeleton (mTORC2). My postdoctoral work showed that the regulation of mTOR-dependent translation contributes to dendritogenesis (Jaworski et al., 2005). However, the list of cellular processes that involve both mTORCs has expanded, and new ways of regulating mTORC activity, novel mTOR partners, and mTOR effectors have been discovered. Nonetheless, their contribution to the neuronal functions of mTOR and neuropathology is still poorly understood. Therefore, since the inception of our laboratory, we have sought to identify mTOR partners and regulated proteins that are involved in the neuronal development and characterization of mTOR dysfunction in neuropathology.

To reach our scientific objectives, we have been using a well established, relatively simple, and robust model of the dendritogenesis of neurons that are cultured in vitro. Using this approach, we previously performed both proof-of-principle experiments and unbiased screens that clearly showed that mTOR functions during neuronal development beyond the canonical control of translation (Swiech et al., 2011; Urbanska et al., 2012; Malik et al., 2013; Fig. 1). In one of these screens, we identified β-adaptin, a subunit of AP2 adaptor complex, that is responsible for recruiting endocytic machinery to internalized cargo (Koscielny et al., 2017). Its direct involvement in dendritogenesis in mammalian neurons has not yet been tested. We found that the knockdown of β2-adaptin, an AP2 subunit, reduced the number of dendrites in developing rat hippocampal neurons and decreased AMPA receptor GluA2 subunit levels by inhibiting mTOR. The dendritic tree abruption that was caused by β2-adaptin knockdown was rescued by the overexpression of GluA2 or restoration of the activity of the mTOR effector p70S6 kinase (S6K1) (Koscielny et al., 2017). Altogether, this work provided evidence that the AP2 adaptor complex is needed for the dendritogenesis of mammalian neurons and reveals that mTOR-dependent GluA2 biosynthesis contributes to this process (Fig. 1).

In 2016, we also finalized another project that is related to mTOR and dendritogenesis but focuses on mTORC2 activation. In our previous work, we identified Zipcode binding protein 1 (ZBP1) as a key regulator of the dendritic arborization of hippocampal neurons (Perycz et al., 2011). In our recent study, we found that ZBP1 in neurons is phosphorylated at Ser181 in an mTORC2-, Src kinase-, and mRNA binding-dependent manner (Urbanska et al., under revision). Ser181 ZBP1 phosphorylation was essential for the proper dendritic branching of hippocampal neurons that were cultured in vitro and for the proper dendritic distribution and motility of ZBP1 through regulation of the interaction between ZBP1 and molecular motor Kif5a. This study demonstrated that protein phosphorylation by mTORC2 regulates protein binding to molecular motors and transport along microtubules.

Finally, in 2016, we concluded a collaborative project with the Hoogenraad Lab that focused on the mechanism of selective cargo steering to dendrites during development. In this study, we searched for kinesins that would be particularly important for selective transport to dendrites. We found that the majority of kinesins steered cargo into axons, but we also found that KIF1 and KIF21 target dendrites as well (Lipka et al., 2016). Microtubule-binding protein Doublecortin-like kinase 1 (DCLK1) labeled dendritic microtubules and was required for selected cargo trafficking into dendrites and dendrite development.



Fig. 1. Upstream regulators and downstream effectors of mTOR in dendritogenesis identified by LMCN team. (1) Jaworski et al. (2005) J.Neurosci., 25:11300-12 (2) Urbanska et al. 2012 J.Biol.Chem., 287:30240-56 (3) Swiech et al. 2011 J.Neurosci., 31:4555-68 (4) Malik et al. 2013 J.Biol.Chem., 288:8544-59 (5) Skalecka, Liszewska et al 2016 Dev. Neurobiol., 76:1308-1327 (6) Koscielny et al. 2017 Mol. Neurobiol., Epub ahead of print.

 

Lab Leader:
Jacek Jaworski, PhD, DSc Habil

Postdoctoral Fellows:
Agnieszka Brzozowska, PhD
Bartosz Tarkowski, PhD
Ewa Liszewska, PhD
Justyna Zmorzyńska, PhD
Magdalena Błażejczyk, PhD
Matylda Macias, PhD
Michalina Wężyk, PhD
Aleksandra Janusz-Kamińska, PhD
Małgorzata Urbańska, PhD

Junior Researchers:
Aleksandra Tempes
Katarzyna Kisielewska
Magdalena Kędra
Alicja Kościelny
Jan Węsławski
Katarzyna Rydz
Hadi Mirzapourdelavar
Marcelina Firkowska

Lab and Office Manager:
Marcelina Firkowska

Technician:
Alina Zielińska 

Student:
Katarzyna Banasiak

Past lab members:
Małgorzata Perycz,  PhD
Anna Urbańska,  PhD
Agnieszka Skałecka,  PhD
Agnieszka Haręza,  PhD
Agata Góźdź,  PhD
Kamil Parobczak, MSc
Łukasz Świech,  PhD
Patrycja Pietruszka, MSc
Anna Malik,  PhD
Małgorzata Zarębska, MSc
Iwona Cymerman,  PhD
Paweł Krawczyk, MSc
Joanna Lipka,  PhD
Anna Bajur, MSc
Adrianna Łach, MSc
Aleksandra Lew, MSc
Lidia Wolińska, MSc
Kamila Jączyńska, MSc

 

2018

Firkowska M, Macias M, Jaworski J.

ESCRT Proteins Control the Dendritic Morphology of Developing and Mature Hippocampal Neurons.

Hareza A, Bakun M, Świderska B, Dudkiewicz M, Koscielny A, Bajur A, Jaworski J, Dadlez M, Pawłowski K.

Phosphoproteomic insights into processes influenced by the kinase-like protein DIA1/C3orf58.

Koscielny A, Malik AR, Liszewska E, Zmorzynska J, Tempes A, Tarkowski B, Jaworski J

Adaptor Complex 2 Controls Dendrite Morphology via mTOR-Dependent Expression of GluA2

2017

Kondratiuk I, Łęski S, Urbańska M, Biecek P, Devijver H, Lechat B, Van Leuven F, Kaczmarek L, Jaworski T

GSK-3β and MMP-9 Cooperate in the Control of Dendritic Spine Morphology

Blazejczyk M, Macias M, Korostynski M, Firkowska M, Piechota M, Skalecka A, Tempes A, Koscielny A, Urbanska M, Przewlocki R, Jaworski J

Kainic Acid Induces mTORC1-Dependent Expression of Elmo1 in Hippocampal Neurons

Switon K, Kotulska K, Janusz-Kaminska A, Zmorzynska J, Jaworski J

Molecular neurobiology of mTOR

Kononenko NL, Claßen GA, Kuijpers M, Puchkov D, Maritzen T, Tempes A, Malik AR, Skalecka A, Bera S, Jaworski J, Haucke V

Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration

de Hoz L, Gierej D, Lioudyno V, Jaworski J, Blazejczyk M, Cruces-Solís H, Beroun A, Lebitko T, Nikolaev T, Knapska E, Nelken I, Kaczmarek L

Blocking c-Fos Expression Reveals the Role of Auditory Cortex Plasticity in Sound Frequency Discrimination Learning

Urbanska AS, Janusz-Kaminska A, Switon K, Hawthorne AL, Perycz M, Urbanska M, Bassell GJ, Jaworski J

ZBP1 phosphorylation at serine 181 regulates its dendritic transport and the development of dendritic trees of hippocampal neurons

Gozdz A, Nikolaienko O, Urbanska M, Cymerman IA, Sitkiewicz E, Blazejczyk M, Dadlez M, Bramham CR, Jaworski J

GSK3α and GSK3β Phosphorylate Arc and Regulate its Degradation

Urbanska M, Gozdz A, Macias M, Cymerman IA, Liszewska E, Kondratiuk I, Devijver H, Lechat B, Van Leuven F, Jaworski J.

GSK3β Controls mTOR and Prosurvival Signaling in Neurons.

2016

Wasiak I, Kulikowska A, Janczewska M, Michalak M, Cymerman IA, Nagalski A, Kallinger P, Szymanski WW, Ciach T

Dextran Nanoparticle Synthesis and Properties

Lipka J, Kapitein LC, Jaworski J, Hoogenraad CC

Microtubule-binding protein doublecortin-like kinase 1 (DCLK1) guides kinesin-3-mediated cargo transport to dendrites

Kevenaar JT, Bianchi S, van Spronsen M, Olieric N, Lipka J,Frias CP, Mikhaylova M, Harterink M, Keijzer N, Wulf PS, Hilbert M, Kapitein LC, de Graaff E, Ahkmanova A, Steinmetz MO, Hoogenraad CC

Kinesin-Binding Protein Controls Microtubule Dynamics and Cargo Trafficking by Regulating Kinesin Motor Activity

van Scheppingen J, Iyer AM, Prabowo AS, Mühlebner A, Anink JJ, Scholl T, Feucht M, Jansen FE, Spliet WG, Krsek P, Zamecnik J, Buccoliero AM, Giordano F, Genitori L, Kotulska K, Jozwiak S, Jaworski J, Liszewska E, van Vliet EA, Aronica E

Expression of microRNAs miR21, miR146a, and miR155 in tuberous sclerosis complex cortical tubers and their regulation in human astrocytes and SEGA-derived cell cultures

Skałecka A, Liszewska E, Bilinski R, Gkogkas C, Khoutorsky A, Malik AR, Sonenberg N, Jaworski J

mTOR kinase is needed for the development and stabilization of dendritic arbors in newly born olfactory bulb neurons

Switon K, Kotulska K, Janusz-Kaminska A, Zmorzynska J, Jaworski J

Tuberous sclerosis complex: From molecular biology to novel therapeutic approaches

Jasińska M, Miłek J, Cymerman IA, Łęski S, Kaczmarek L, Dziembowska M

miR-132 Regulates Dendritic Spine Structure by Direct Targeting of Matrix Metalloproteinase 9 mRNA

Kędra M, Jaworski J, Zmorzyńska J.

Okiem ryby - nowe spojrzenie na rozwój sieci neuronalnych i choroby neurorozwojowe.

2015

Cymerman IA, Gozdz A, Urbanska M, Milek J, Dziembowska M, Jaworski J

Structural Plasticity of Dendritic Spines Requires GSK3α and GSK3βMistargeted mitochondrial proteins activate a proteostatic response in the cytosol

Malik AR, Liszewska E, Jaworski J

Matricellular proteins of the Cyr61/CTGF/NOV (CCN) family and the nervous system

Malik AR, Liszewska E, Skalecka A, Urbanska M, Iyer AM, Swiech LJ, Perycz M, Parobczak K, Pietruszka P, Zarebska MM, Macias M, Kotulska K, Borkowska J, Grajkowska W, Tyburczy ME, Jozwiak S, Kwiatkowski DJ, Aronica E, Jaworski J

Tuberous sclerosis complex neuropathology requires glutamate-cysteine ligase

Esteves da Silva M, Adrian M, Schätzle P, Lipka J, Watanabe T, Cho S, Futai K, Wierenga CJ, Kapitein LC, Hoogenraad CC

Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture

Kulcenty K, Wróblewska J, Mazurek S, Liszewska E, Jaworski J.

Molecular mechanisms of induced pluripotency.

2014

Skupien A, Konopka A, Trzaskoma P, Labus J, Gorlewicz A, Swiech L, Babraj M, Dolezyczek H, Figiel I, Ponimaskin E, Wlodarczyk J, Jaworski J, Wilczynski GM, Dzwonek J

CD44 regulates dendrite morphogenesis through Src tyrosine kinase-dependent positioning of the Golgi

Geiger JC, Lipka J, Segura I, Hoyer S, Schlager MA, Wulf PS, Weinges S, Demmers J, Hoogenraad CC, Acker-Palmer A

The GRIP1/14-3-3 Pathway Coordinates Cargo Trafficking and Dendrite Development

2013

Malik AR, Urbanska M, Macias M, Skalecka A, Jaworski J

Beyond control of protein translation: What we have learned about the non-canonical regulation and function of mammalian target of rapamycin (mTOR)

Malik AR, Urbanska M, Gozdz A, Swiech LJ, Nagalski A, Perycz M, Blazejczyk M, Jaworski J

CYR61, a matricellular protein, is needed for dendritic arborization of hippocampal neurons

van Spronsen M, Mikhaylova M, Lipka J, Schlager MA, van den Heuvel DJ, Kuijpers M, Wulf PS, Keijzer N, Demmers J, Kapitein LC, Jaarsma D, Gerritsen HC, Akhmanova A, Hoogenraad CC

TRAK/Milton Motor-Adaptor Proteins Steer Mitochondrial Trafficking to Axons and Dendrites

Kuzniewska B, Rejmak E, Malik AR, Jaworski J, Kaczmarek L, Kalita K

Brain-derived neurotrophic factor induces matrix metalloproteinase-9 expression in neurons via serum response factor/c-Fos pathway

Kapitein LC, van Bergeijk P, Lipka J, Keijzer N, Wulf PS, Katrukha EA, Akhmanova A, Hoogenraad CC

Myosin-V Opposes Microtubule-Based Cargo Transport and Drives Directional Motility on Cortical Actin

Macias M, Blazejczyk M, Kazmierska P, Caban B, Skalecka A, Tarkowski B, Rodo A, Konopacki J, Jaworski J

Spatiotemporal Characterization of mTOR Kinase Activity Following Kainic Acid Induced Status Epilepticus and Analysis of Rat Brain Response to Chronic Rapamycin Treatment

Bedzhov I, Alotaibi H, Basilicata MF, Ahlborn K,Liszewska E, Brabletz T, Stemmler MP

Adhesion, but not a specific cadherin code, is indispensable for ES cell and induced pluripotency

Janusz A, Milek J, Perycz M, Pacini L, Bagni C, Kaczmarek L, Dziembowska M

The fragile x mental retardation protein regulates matrix metalloproteinase 9 mRNA at synapses

Lipka J, Kuijpers M,Jaworski J, Hoogenraad CC

Mutations in cytoplasmic dynein and its regulators cause malformations of cortical development and neurodegenerative diseases

Liszewska E, Jaworski J

Why do we need induced pluripotent stem cells in neurobiology?

Jaworski J

Uchwytny kształt pamięci

2012

Urbanska M, Swiech L, Jaworski J

Developmental plasticity of the dendritic compartment: focus on the cytoskeleton

Urbanska M, Gozdz A, Swiech LJ, Jaworski J

Mammalian target of rapamycin complex 1 (MTORC1) and 2 MTORC2) control the dendritic arbor morphology of hippocampal neurons

Knapska E, Macias M, Mikosz M, Nowak A, Owczarek D, Wawrzyniak M, Pieprzyk M, Cymerman IA, Werka T, Sheng M, Maren S, Jaworski J, Kaczmarek L

Functional anatomy of neural circuits regulating fear and extinction

2011

Werner M, Purta E, Kaminska KH, Cymerman IA, Campbell DA, Mittra B, Zamudio JR, Sturm NR, Jaworski J, Bujnicki JM

2'-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family

Azoulay-Alfaguter I, Yaffe Y, Licht-Murava A, Urbanska M, Jaworski J, Pietrokovski S, Hirschberg K, Eldar-Finkelman H

Distinct molecular regulation of glycogen synthase kinase-3alpha isozyme controlled by its N-terminal region: functional role in calcium/calpain signaling

Swiech L, Blazejczyk M, Urbanska M, Pietruszka P, Dortland BR, Malik AR, Wulf PS, Hoogenraad CC, Jaworski J

CLIP-170 and IQGAP1 cooperatively regulate dendrite morphology

Perycz M, Urbanska AS, Krawczyk PS, Parobczak K, Jaworski J

Zipcode binding protein 1 regulates the development of dendritic arbors in hippocampal neurons

Kapitein LC, Yau KW, Gouveia SM, van der Zwan WA, Wulf PS, Keijzer N, Demmers J, Jaworski J, Akhmanova A, Hoogenraad CC

NMDA Receptor Activation Suppresses Microtubule Growth and Spine Entry

2010

Stefaniuk M, Swiech L, Dzwonek J, Lukasiuk K

Expression of Ttyh1, a member of the Tweety family in neurons in vitro and in vivo and its potential role in brain pathology.

Kieper J, Lauber C, Gimadutdinow O, Urbańska A, Cymerman I, Ghosh M, Szczesny B, Meiss G

Production and characterization of recombinant protein preparations of Endonuclease G-homologs from yeast, C. elegans and humans.

Piechota M, Korostynski M, Solecki W, Gieryk A, Slezak M, Bilecki W, Ziolkowska B, Kostrzewa E, Cymerman I, Swiech L, Jaworski J, Przewlocki R

The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum.

2009

Blazejczyk M, Sobczak A, Debowska K, Wisniewska MB, Kirilenko A, Pikula S, Jaworski J, Kuznicki J, Wojda U.

Biochemical characterization and expression analysis of a novel EF-hand Ca2+ binding protein calmyrin2 (Cib2) in brain indicates its function in NMDA receptor mediated Ca2+ signaling.

Jaworski J, Kapitein LC, Gouveia SM, Dortland BR, Wulf PS, Grigoriev I, Camera P, Spangler SA, Di Stefano P, Demmers J, Krugers H, Defilippi P, Akhmanova A, Hoogenraad CC

Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity.

2008

Mioduszewska B, Jaworski J, Szklarczyk AW, Klejman A, Kaczmarek L

Inducible cAMP early repressor (ICER)-evoked delayed neuronal death in the organotypic hippocampal culture

Urbanska M, Blazejczyk M, Jaworski J

Molecular basis of dendritic arborization

Macias M

Injury induced dendritic plasticity in the mature central nervous system.

Swiech L, Perycz M, Malik A, Jaworski J

Role of mTOR in physiology and pathology of the nervous system

Jaworski J, Hoogenraad CC, Akhmanova A

Microtubule plus-end tracking proteins in differentiated mammalian cells.

Rylski M, Amborska R, Zybura K, Mioduszewska B, Michaluk P, Jaworski J, Kaczmarek L

Yin Yang 1 is a critical repressor of matrix metalloproteinase-9 expression in brain neurons

Tomat E, Nolan EM, Jaworski J, Lippard SJ

Organelle-specific zinc detection using zinpyr-labeled fusion proteins in live cells

2007

Okulski P, Jay TM, Jaworski J, Duniec K, Dzwonek J, Konopacki FA, Wilczynski GM, Sánchez-Capelo A, Mallet J, Kaczmarek L

TIMP-1 abolishes MMP-9-dependent long-lasting long-term potentiation in the prefrontal cortex.

Michaluk P, Kolodziej L, Mioduszewska B, Wilczynski GM, Dzwonek J, Jaworski J, Gorecki DC, Ottersen OP, Kaczmarek L

Beta-dystroglycan as a target for MMP-9, in response to enhanced neuronal activity.

Jaworski J

ARF6 in the nervous system.

2006

Szymczak S, Kalita K, Jaworski J, Mioduszewska B, Savonenko A, Markowska A, Merchenthaler I, Kaczmarek L

Increased estrogen receptor beta expression correlates with decreased spine formation in the rat hippocampus

Nolan EM, Ryu JW, Jaworski J, Feazell RP, Sheng M, Lippard SJ

Zinspy sensors with enhanced dynamic range for imaging neuronal cell zinc uptake and mobilization.

Jaworski J, Sheng M

The growing role of mTOR in neuronal development and plasticity