Leader

Jacek Kuźnicki, PhD, Professor

Leader

We study the molecular and cellular roles of calcium, potassium and ferrum and associated molecules in development and in nervous system pathologies. Our main focus is neurodegeneration in Parkinson disease (PD), as well as epileptic encephalopathy, hearing loss, and retinal pathology. We use cultured iPSC-derived human neurons and zebrafish models of these pathologies. 

Research Summary

PD is an incurable neurodegenerative disorder. Its pathological hallmarks include alpha-synuclein aggregation and loss of dopaminergic neurons. In various PD animal models and in cells from PD patients, calcium and iron ions homeostasis is perturbed. Our major research focus is on Ca2+-dependent mechanisms and Fe2+-dependent ferroptosis involved in the development of PD. 

There are three types of PD : the most prevalent sporadic PD form with late onset, familial PD caused by mutations in genes such as PINK1 or LRRK2, and environmentally induced PD caused by exposure to toxic agents such as MPTP or rotenone. 

Our published data show that degeneration of dopaminergic neurons in zebrafish PD models caused by the pink1 mutation or MPTP toxicity can be rescued by inactivation of the mitochondrial calcium uniporter (MCU). This membrane transport protein moves calcium ion across a cell membrane down its concentration gradient without using cellular energy (ATP). Other studies have shown that MCU inhibition also rescues neurons carrying an LRRK2 mutation. 

If different factors that cause PD have a common denominator related to MCU activity, it is essential to understand the mechanism of this protection. Our hypothesis is that MCU inactivation turns specific genes on or off, probably including genes involved in ferroptosis, thereby supporting the survival of dopaminergic neurons. The main goal of the project is to identify ferroptosis-associated genes that are dysregulated in pink1 and lrrk2 PD zebrafish models and in human iPSC-derived neurons upon rescue of dopaminergic neurons by MCU inactivation.

Scientific Impact

• We showed that the loss of dopaminergic neurons in PD zebrafish models can be delayed by inhibiting the mitochondrial calcium uniporter (MCU). 
• We showed that the loss of the Ca2+ sensor Stim2 in zebrafish induces a glaucoma-like phenotype. 
• Research on calcium and iron homeostasis may help identify mechanisms responsible for PD pathology. 
• Parkinson disease research in the Laboratory of Neurodegeneration received a private donation of PLN 1 million. 
• Prof. Jacek Kuźnicki received the Minister of Science and Higher Education Award for lifetime achievements.   

Future Goals

• The developmental role of identified MCU-regulated genes induced during ferroptosis will be studied using the PD patient-derived iPS cells and the zebrafish disease models. 
• We will analyze the molecular mechanisms responsible for the loss of retinal ganglion cells in stim2 zebrafish knockout models. 
• We will identify  the regulatory regions of the human SLC26A4 gene, which encodes Pendrin , a sodium-independent chloride-iodide ion exchanger, whose polymorphism has been associated with CEVA (Caucasian Enlarged Vestibular Aqueduct), a common inner ear abnormality causing sensorineural hearing loss. 

Comment

"In various animal models of Parkinson disease and in cells from PD patients, perturbations of calcium and iron homeostasis occur. Studying these processes may identify mechanisms responsible for PD pathology. We use iPSC-differentiated dopaminergic neurons and zebrafish with Pink1 and Lrrk2 mutations." - Prof. Jacek Kuźnicki 

The graphical abstract presents the research hypothesis showing how inactivation of the MCU may protect dopaminergic neurons. Illustration: Prof. Jacek Kuźnicki. 

About the lab

Jacek Kuźnicki, PhD, Professor  Correspondence address: Laboratory of Neurodegeneration 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.

DEGREES

1993 - Professor, awarded by the President of the Republic of Poland
1987 - DSc. Habil., Nencki Institute of Experimental Biology PAS, Warsaw, Poland
1980 - PhD in biochemistry, Nencki Institute of Experimental Biology PAS, Warsaw, Poland
1976 - MSc in biochemistry, Faculty of Biology, University of Warsaw, Poland

PROFESSIONAL EXPERIENCE

2001-present - Professor, Head of Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Poland
2020-2022 - President of the National Science Centre Council, member 2018-2022
2001-2018 - Director, International Institute of Molecular and Cell Biology in Warsaw, Poland; Feb-Dec 2018 Acting Director, International Institute of Molecular and Cell Biology in Warsaw, Poland
2017-2018 - Deputy Chair of the Council of Provosts, 2nd Division: Biological and Agricultural Sciences, Polish Academy of Sciences
2000-2001 - Director, Centre of Excellence Phare Sci-Tech II, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
1999-2001 - Acting Director, International Institute of Molecular and Cell Biology in Warsaw, Poland; Organizer and Director, Centenarian Program
1996-2002 - Head, Laboratory of Calcium Binding Proteins, professor 2002- 2014 Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
1992-1995 - Visiting Professor, NIMH, Bethesda, MD, USA
1991-1992 - Deputy Scientific Director, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
1986-1992 - Associate Professor and Head of Laboratory of Calcium Binding Proteins, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
1984-1985 - Research Associate, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
1981-1984 - Visiting Fellow, NIH, Bethesda, MD, USA
1980-1981 - Post-doctoral Fellow, Nencki Institute
1976-1980 - PhD Student, Nencki Institute of Experimental Biology PAN, Warsaw

PROFESSIONAL TRAINING

2018, July - Visiting Professor, Laboratory of H. Burgess, National Institute of Child Health and Human Development, Bethesda, MD, USA
2015, July - Visiting Professor, Laboratory of W. Harris, University of Cambridge, UK 
2014, July - Visiting Professor, Laboratory of B.E. Snaar-Jagalska, Leiden University, The Netherlands
1992-1995 - Visiting Professor, Laboratory of D. Jacobowitz, National Institute of Mental Health, Bethesda, MD, USA
1981-1984 - Visiting Fellow (postdoc), Laboratory of E.D. Korn, National Institute of Heart, Lung and Blood, Bethesda, MD, USA

MEMBERSHIP IN SCIENTIFIC SOCIETIES, ORGANIZATIONS, AND PANELS

2020-present - External expert in biotechnology, Łukasiewcz Research Network - PORT Polish Center for Technology Development
2020-present - Ordinary Member, Polish Academy of Sciences
2016-2021 - Member, International Advisory Board, Małopolska Centre of Biotechnology, Jagiellonian University
2011-present - Member, International Expert Council of the Research and Education Center, State Key Laboratory of Molecular and Cellular Biology, Ukraine
2011-2014 - Member, Science Policy Committee, and Rotating President (Jul-Dec 2012), Ministry of Science and Higher Education
2008-2022 - Board Member, European Calcium Society, member since 1997
2008-2018 - Member, Board of Directors, and Rotating President (Jul-Dec 2016, Jul-Dec 2013, Jul-Dec 2010), Biocentrum-Ochota Consortium
2006-2011 - Member, Advisory Group, 7FP HEALTH, European Commission
2004-2019 - Corresponding Member, Polish Academy of Sciences
2004-present - Honorary Chair and co-founder, BioEducation Foundation
2002-present - Head of Program Board, Centre for Innovative Bioscience Education
1993-2014 - Member, Scientific Council, Nencki Institute of Experimental Biology, Polish Academy of Sciences
1996-1998 & 2000-2002 - Vice-President, Biotechnology Committee, Polish Academy of Sciences
1989 - 1991 - General Secretary, Polish Biochemical Society, member since 1977

HONORS, PRIZES AND AWARDS

2018 - Commemorative medal for the 100^th Anniversary of the Nencki Institute for outstanding contribution to the development of this Institute, supporting its activities, shaping the image and building a mutual success
2013 - Crystal Brussels Prize for outstanding achievements in 7^th Framework Programme of the European Union for Research and Development
2013 - Award from the 2nd Division of Biological and Agricultural Sciences, Polish Academy of Sciences for series of works on β-catenin
2011 - Konorski Award for the best Polish research work in neurobiology awarded by the Polish Neuroscience Society and Committee on Neurobiology of the PAS
2008 - Officer's Cross of the Order of Polonia Restituta awarded by the President of Poland
2004-2007 - Professorial Subsidy Program Award from Foundation for Polish Science
2003 - Prime Minister Award for the scientific achievements, Warsaw
2001 - Award from the Division of Biological Sciences of the PAS for the work on CaBP
1998 - Knight's Cross of the Order of Polonia Restituta awarded by the President of  Poland
1987 - Polish Anatomical Society Award for the article in “Advances in Cell Biology”
1986 - Skarzynski Award from the Polish Biochemical Society for the best review article in “Advances in Biochemistry”
1977 - Mozolowski Award, Polish Biochem. Society for outstanding Polish young biochemist
1977 - Parnas Award from Polish Biochem. Society for the best paper in biochemical research
1976 - MSc, Magna cum laude, University of Warsaw

DOCTORATES DEFENDED UNDER LAB LEADER’S SUPERVISION

A. Filipek, J. Kordowska, U. Wojda, J. Hetman, M. Palczewska, M. Nowotny, K. Billing-Marczak, Ł. Bojarski, W. Michowski, K. Misztal, M. Figiel, K. Honarnejad, A. Jaworska, K. Gazda, F. Maciąg, J. Jędrychowska, I. Wasilewska, RK. Gupta.

Group members

Lab Leader
Jacek Kuźnicki, PhD, Professor

Senior Researchers
Vladimir Korzh, PhD, DSc Habil

Postdoctoral Researchers
Weronika Skarżyńska, PhD
Narges Sotoudeh, PhD
Krystyna Żyżyńska-Galeńska, PhD

PhD Students
Sofiia Baranykova, MSc

Research Assistants
Aleksandra Moskal, MSc

Volunteers
Magdalena Czeredys, PhD, DSc Habil (from Mossakowski Medical Research Institute PAS)
Iga Wasilewska, PhD (from Mossakowski Medical Research Institute PAS)

Lab Technician
Monika Matuszczyk (part-time)

Laboratory Support Specialist
Dominika Dubicka, MSc

Leader

Matthias Bochtler, PhD, Professor

Leader

We study epigenetics, specifically nucleic acid and histone modifications that influence cell fate change and maintenance. We use a broad spectrum of methods - from different variants of high-throughput sequencing, through classical biochemistry and structural biology, to large-scale data analysis. Our research is relevant to oncology, particularly to understanding hematologic malignancies in which epigenetic disruption plays an important role. 

Research Summary

Our work focuses on 2'-deoxynucleotide modifications and metabolism. We are interested in the integrity of the 2'-deoxynucleotide pool and its potential consequences for epigenetics, particularly in developmental biology and cancer biology contexts. More recently, we have also initiated projects on amino acid metabolism, again in a cancer context. 

The main biological theme of our projects is hematological malignancies. We study, among others, mixed lineage leukemia (MLL), acute myeloid leukemia with complex karyotype (CK-AML), and asparaginase treatment in acute lymphoblastic leukemia (ALL). 

Methodologically, the group uses biochemistry and structural biology, but increasingly also relies on high-throughput sequencing and animal models. This allows us to test the relevance of biochemical concepts in a more physiological setting. 

Scientific Impact

• We have contributed to the understanding of DNA modification pathways. 
• We have identified enzymes that balance or sanitize the 2'-deoxynucleotide pool. 
• We have contributed molecular insights to the biology of MLL and CK-AML. 
• In our work on CDADC1, we showed that human CDADC1 is a (d)CTP-specific deaminase. High-resolution structures explained the enzyme's substrate specificity, while genetic experiments in mice showed that loss of Cdadc1 is well tolerated, even in the absence of Dctd. 

Future Goals

We would like our work to have clinical impact in the future. For this reason, we are developing new clinical collaborations that should help connect our discoveries more closely with the biology of hematological diseases and potential practical applications. 

Collaborations

We collaborate with academic partners, including Prof. G. Xu, Prof. J. Weng, Dr. T. Jurkowski, Dr. T. Hore, Dr. C. Winata, and Dr. A. Wlodawer, as well as with industry representatives, including Dr. P. Weigele. The group is also developing clinical collaborations with Dr. K. Gawle-Krawczyk, Prof. A. Kraemer, Prof. F. Stoelzel, Dr. T. Bochtler, Prof. A. Stenzinger, Prof. O. Neumann, and Dr. D. Kazdal. 

Comment

“After many years of doing purely basic research, it would be nice to also have a practical impact,” says Prof. Matthias Bochtler. 

The team studies epigenetics, nucleic acid modifications, and 2'-deoxynucleotide metabolism, as well as their relevance to cell-fate stability and the development of hematological malignancies. The illustration presents the activity, structure, and function of vertebrate CDADC1: its activity as a (d)CTP deaminase, the structural basis of triphosphate specificity, and observations from the Cdadc1 KO mouse model. 

About the lab

Matthias Bochtler, PhD, Professor  Correspondence address: Laboratory of Structural Biology 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. Office: This email address is being protected from spambots. You need JavaScript enabled to view it. tel: +48 (22) 597 0732; fax: +48 (22) 597 0715

DEGREES

2009 - Professor of Biological Sciences, nomination by the President of the Republic of Poland
2006 - DSc Habil, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland
1999 - PhD in Biochemistry, Technical University of Munich, Germany
1995 - MSc in Experimental Physics, Munich University, Germany

PROFESSIONAL EMPLOYMENT

2011-present - Professor, Head of Laboratory of Structural in Biology, International Institute of Molecular and Cell Biology in Warsaw, Poland, and Laboratory of Genome Engineering, Institute of Biochemistry and Biophysics, Polish Academy of Sciences,Warsaw, Poland
2007-2011 - Part-time Director of Structural Biology, Cardiff University, United Kingdom
2001-2010 - Head, Joint MPG-PAS Junior Research Group, International Institute of Molecular and Cell Biology in Warsaw, Poland
2000 - Patent training, Weickmann & Weickmann
1999-2000 - Postdoctoral Fellow, Max Planck Institute of Biochemistry, Martinsried, Germany

RESEARCH TRAINING

1996-1999 - Research Assistant, Max Planck Institute of Biochemistry, Martinsried, Germany
1995-1996 - Internship, Medical Microbiology, University of Regensburg,  Germany
1992-1993 - Guest Student, Cambridge University, United Kingdom
1990-1992 - Studies in Physics, Munich University, Germany

HONORS, PRIZES AND AWARDS

2023 - Minister of Education and Science Award for significant achievements in scientific activities 
2023 - Włodzimierz Krzyżosiak Distinction awarded by the Polish Academy of Sciences
2018 - TEAM Foundation for Polish Science
2018 - International Academic Partnerships Programme, Polish National Agency for Academic Exchange
2018 - DAINA, National Science Centre
2015 - HARMONIA, National Science Centre
2012 - MAESTRO, National Science Centre
2011 - TEAM, Foundation for Polish Science Professor Stefan Pieńkowski Award
2004 - EMBO/HHMI Young Investigator Award
2000 - Crystal Award, Germany
1998 - Crystal Award Germany
1990 – 1992 - Scholarship from Deutsche Studienstiftung and Bavarian State

DOCTORATES DEFENDED UNDER LAB LEADER’S SUPERVISION

R. Filipek, M. Firczuk, M. Lipka, R. Szczepanowski, M. Kaus-Drobek, M. Sokołowska, G. Chojnowski, H. Korza, M. Wojciechowski, W. Siwek, P. Haniewicz, A.A. Kazrani, K. Mierzejewska.

Group members

Head of Laboratory
Prof. Matthias Bochtler 

Senior Researcher
Honorata Czapińska, PhD, DSc Habil. 

PhD students
Nashat Akhtar, MSc
Terry Karimi, MSc 

Research Specialist
Natalia Leśniowska, MSc 

Lab Technician
Julia Kędzierska, MSc 

Volunteer
Dominik Rafalski, PhD 

Laboratory Support Specialist
Katarzyna Grzelak, PhD 

Contact
This email address is being protected from spambots. You need JavaScript enabled to view it.

Leader

Marta Miączyńska,  PhD, Professor

Leader

We study the functional links between two key intracellular processes: endocytosis and receptor signaling. We seek to understand how cells take up, transport, sort, and process different substances and signals, and how these rules of cellular logistics change under pathological conditions, such as cancer or selected rare diseases. We focus particularly on ESCRT complexes and AXL-dependent macropinocytosis, because disturbances in these processes may reveal vulnerabilities that can be exploited in targeted therapies. 

Research Summary

We are fascinated by how endocytosis and receptor signaling cooperate in healthy cells and in disease states. We investigate how endosomal compartments influence receptor trafficking and signaling, and how alterations in these processes support cancer progression or contribute to the pathogenesis of rare genetic diseases. 

One major research direction concerns the roles of endosomal sorting complexes required for transport, or ESCRT complexes, in cell physiology and oncogenesis. We have shown that endosomal dysfunction caused by loss of proper ESCRT function induces three types of cellular responses: sterile inflammatory signaling, lysosome biogenesis, and metabolic reprogramming towards enhanced use of extracellular nutrients. Together, these findings demonstrate a broad role of ESCRT complexes in coordinating membrane trafficking, signaling, and metabolism. 

The synthetic lethality we identified between two paralogous ATPases of the ESCRT machinery, VPS4A and VPS4B, has uncovered a new pair of potential therapeutic targets for personalized oncology. We also investigate how mutations in ESCRT components found in rare neurological disorders alter cellular functions and may underlie disease pathogenesis. 

In a separate line of research, we focus on macropinocytosis, one of the least characterized routes of endocytic cargo internalization. This pathway is nevertheless crucial for nutrient acquisition by cancer cells. We discovered that the AXL receptor tyrosine kinase, a receptor frequently overexpressed in late-stage and therapy-resistant cancers, is a potent inducer of macropinocytosis. 

Upon activation by its ligand GAS6, AXL drives extensive actin cytoskeleton remodeling, promoting the formation of dynamic membrane ruffles. These ruffles extend and close to generate macropinosomes - large, irregular vesicles containing extracellular fluid and associated cargo, such as nutrients, growth factors, and membrane receptors. Newly formed macropinosomes subsequently mature through sequential fusion and fission events with endosomal compartments, enabling the sorting, degradation, or recycling of internalized material. Building on our identification of AXL-interacting proteins, we are currently characterizing the effectors and regulators that mediate macropinocytosis.

Scientific Impact

Our studies provide proof of concept that intracellular trafficking and the molecules regulating it can represent viable therapeutic targets in personalized oncology. For example, the synthetic lethality between VPS4A and VPS4B ATPases provides a rationale for developing VPS4 inhibitors for the precision treatment of VPS4B-deficient cancers. 

At the same time, our ongoing studies of AXL-dependent macropinocytosis aim to uncover ways of blocking this process in metastatic and drug-resistant cancers with AXL overexpression. Work on mutations in ESCRT components found in rare neurological diseases also helps explain how disrupted cellular logistics can translate into pathology at the cellular and tissue levels. 

Future Goals

We wish to understand how altered expression or mutations of ESCRT components, observed in cancer and some rare diseases, modify cell physiology. In parallel, we aim to elucidate the mechanisms and effector proteins by which the activated AXL receptor drives macropinocytosis and fuels cancer-cell growth. 

Collaborations

We collaborate with partners from IIMCB and external institutions within the HERO consortium project, which aims to develop the next generation of mRNA-based cancer immunotherapies. Prof. Marta Miączyńska also coordinates the research area focused on advanced models of rare diseases in RACE-PRIME, a project aimed at developing innovative therapeutic strategies for diseases where current treatment options remain inadequate or unavailable. 

Comment

In 2024-2025, we continued to study the principles of cellular logistics: how cells take up and transport various substances within their interior, and which signals initiate these processes. Our aim was to understand how these trafficking rules are altered in disease, for example, in cancer cells with increased metabolic demands or in cells carrying mutations that cause rare genetic disorders. We believe that elucidating these underlying mechanisms can ultimately guide the development of new therapeutic strategies. - Prof. Marta Miączyńska 

Murine bone marrow-derived macrophages cultured in vitro. Nuclei are stained blue, endosomes green, nucleoli magenta, and actin gray. Image by Patrycja Daszczuk.

Transmission electron microscopy image of membrane organelles - a multivesicular endosome containing internal vesicles and mitochondria - in a HEK293 cell. Image by Ewelina Szymańska, Matylda Macias, Aleksandra Szybińska. 

About the lab

Marta Miączyńska, PhD, Professor  Correspondence address: Laboratory of Cell Biology 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.

DEGREES

2013 - Professor of Biological Sciences, nominated by the President of the Republic of Poland
2008 - DSc Habil in Cell Biology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
1997 - PhD in Genetics, University of Vienna, Austria
1993 - MSc in Molecular Biology, Jagiellonian University, Cracow, Poland
1991 - BSc in Biological Sciences, University of Wolverhampton, UK

PROFESSIONAL EMPLOYMENT

2018-present - Director, International Institute of Molecular and Cell Biology in Warsaw, Poland
2014-2015 - Deputy Director for Science, International Institute of Molecular and Cell Biology in Warsaw, Poland
2013-2014 - Deputy Director, International Institute of Molecular and Cell Biology in Warsaw, Poland
2005-present - Professor, Head of Laboratory of Cell Biology, International Institute of Molecular and Cell Biology in Warsaw, Poland

RESEARCH TRAINING

2001-2005 - Senior Postdoctoral Fellow, Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG), Dresden, Germany
1997-2000 - Postdoctoral training, European Molecular Biology Laboratory, Heidelberg, Germany
1993-1996 - PhD studies, Institute of Microbiology and Genetics, University of Vienna, Austria
1990-1991 - Exchange Student, University of Wolverhampton, UK

HONORS, PRIZES AND AWARDS

2024 - Vice Chair of the EMBO Council
2024 - Co-Chair of EU-LIFE Alliance
2021 - Prime Minister's Award for outstanding scientific achievements
2021 - Member, EMBO Council
2020 - Corresponding Member, Polish Academy of Sciences
2019 - Member, Academia Europaea
2017 - Member, European Molecular Biology Organization
2016-2018 - Member, Council of the National Science Centre
2016 - TEAM, Foundation for Polish Science
2012 - MAESTRO, National Science Centre
2011 - Polish-Swiss Research Programme grant
2007 - Habilitation Fellowship of L’Oréal Poland for Women in Science
2006-2012 - International Senior Research Fellowship, Wellcome Trust
2006-2010 - International Research Scholar, Howard Hughes Medical Institute, USA
2006-2010 - Partner Group grant, Max Planck Society, Germany
2001-2004 - Postdoctoral Fellowship, Max Planck Society, Germany
1999-2000 - Long-Term Postdoctoral Fellowship, Human Frontier Science Program Organization
1998-1999 - Erwin Schrödinger Postdoctoral Fellowship, Austrian Science Fund
1993-1996 - Bertha von Suttner PhD Scholarship, Austrian Ministry of Science
1990-1991 - Studentship, European Community Tempus Scheme

DOCTORATES DEFENDED UNDER LAB LEADER’S SUPERVISION

M. Olchowik, A. Urbańska, A. Hupałowska, Ł. Sadowski, A. Mamińska, A. Toruń, K. Jastrzębski, M. Maksymowicz, K. Wojciechowska, A. Poświata, M. Wróbel.

Group members

Lab Leader:
Marta Miączyńska, PhD, Professor

Senior Researcher:
Ewelina Szymańska, PhD

Postdoctoral Researchers:
Patrycja Daszczuk, PhD
Ranjana Maurya, PhD

PhD Students:
Marta Chwałek, MSc
Malwina Grębowicz-Maciukiewicz, MSc
Bartosz Jary, MSc
Zuzanna Miciak, MSc

Research Assistant:
Agnieszka Świstek, MSc

Master's Students:
Anna Witowska (BSc)

Lab Technician:
Monika Matuszczyk (part-time)

Laboratory Support Specialist:
Renata Wyszyńska, MSc

Leader

Jacek Jaworski, PhD, Professor

Leader

A major focus of our research is neuronal morphology, because neuronal shape is a key determinant of function. To better understand the molecular mechanisms underlying neuronal development, we study the function of the mTOR kinase. However, neuronal architecture changes not only during development but also during aging and disease processes in the adult brain, including depression. For this reason, in recent years we have also focused on molecular mechanisms that stabilize dendrites and on how this stability is disrupted in the mature nervous system. 

Research Summary 

Since the establishment of the laboratory, we have studied the role of the mTOR kinase in neurons, particularly in nervous system development. Dysregulation of mTOR activity leads to neurodevelopmental disorders such as tuberous sclerosis complex. mTOR is a central regulator of cellular metabolism: it integrates information about cellular energy status, amino acid availability, and extracellular signals, including trophic factors. 

In recent years, our work has addressed mTOR-dependent processes such as translation, transcription, autophagy, and intracellular trafficking. All of these processes are important for proper neuronal development and function. We now focus particularly on mTOR functions in the cell nucleus - a non-canonical and still poorly characterized localization. We have shown that in neurons, mTOR accumulates in the nucleus in response to increased neuronal activity. 

In parallel, we study mechanisms responsible for the stability of mature neuronal morphology. In this area, we identified mTOR as one of the key regulators. We have also discovered new proteins involved in stabilizing neuronal architecture, including ITPKA, whose molecular functions in this context are now under investigation.

Scientific Impact 

• Demonstrating that inhibition of mTOR activity via activation of autophagy regulates lysosome transport along microtubules. 
• Identifying dilazep and penbutolol through screening approaches as candidate antidepressant compounds; a patent application is pending. 
• Advancing knowledge of non-canonical functions of mTOR in the neuronal cell nucleus. 
• Identifying new proteins involved in dendritic stabilization and destabilization in the adult nervous system

Future Goals

Our main goal for the coming years is the comprehensive characterization of nuclear mTOR in brain development, physiology, and pathology. We aim to determine how this non-canonical pool of mTOR affects neuronal function and how its disruption may contribute to diseases of the nervous system. 

In parallel, we will continue to investigate the molecular mechanisms controlling dendritic stability and destabilization in the adult nervous system, particularly in the context of depression and other disorders associated with altered neuronal architecture. 

Collaborations

Our key collaborators include Prof. Kathrin Thedieck, Prof. Sergiusz Jóźwiak, Prof. Katarzyna Kotulska, Prof. David Kwiatkowski, Prof. Eleonora Aronica, Prof. Leszek Kaczmarek, and Prof. Ewelina Knapska. Together, we work to understand how molecular mechanisms translate into clinical features of tuberous sclerosis complex and depression, and how this knowledge can be used to help patients. 

Awards and Recognition 

2020 - Polish Prime Minister Award for scientific achievement
2021 - 2nd Division (Biological Sciences) of Polish Academy of Sciences Award for a series of publications on mTOR and novel therapeutic targets in TSC
2023 - election to the European Molecular Biology Organization
2024 - Herbert Resner Award for research that demonstrated a potential new therapy for tuberous sclerosis.
2025 - election to the Polish Academy of Sciences 

Comment

"Our research focuses on the molecular basis of the development and stability of neuronal networks. In particular, we focus on the molecular functions of the mTOR protein, which may enable better diagnosis and potential therapy of mTORopathies, diseases caused by mTOR hyperactivity," says Prof. Jacek Jaworski.

Rat hippocampal neurons cultured in vitro. Immunofluorescence labeling shows GluA1 in green, Bassoon in red, and cell nuclei in blue. Illustration by Karolina Protokowicz.

About the lab

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

PROFESSIONAL EXPERIENCE

2018-present - Deputy Director for Science, International Institute of Molecular and Cell Biology in Warsaw, Poland
2010 - 2013 - Deputy Director, International Institute of Molecular and Cell Biology in Warsaw, Poland
2005-present - Professor, Head of Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology in Warsaw, Poland

RESEARCH TRAINING

2016 - Research visit (3 weeks) with Prof. William Harris, Cambridge University, Cambridge, UK
2011 - Research visit (2 weeks) with Dr. Carlo Sala, CNR Institute of Neuroscience and Instituto Neurologico Carlo Besta, Milan, Italy
2006 - Research visit (1 month) 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

2018 - TEAM, Foundation for Polish Science
2014 - Master Award, Foundation for Polish Science
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)

MEMBERSHIP IN SCIENTIFIC SOCIETIES, ORGANIZATIONS, AND PANELS

2019 - Member, Scientific Advisory Board of the Institute of Pharmacology, Polish Academy of Sciences
2017 - Vice President, Polish Neuroscience Society (term 2017-2019)
2015 - Corresponding Member, Warsaw Scientific Society
2015 - Member, Scientific Advisory Board of the Nencki Institute of Experimental Biology, Polish Academy of Sciences
2011 - Member, Neurobiology Committee, Polish Academy of Sciences (terms 2011-2014; 2015-2018; 2019-2020)

DOCTORATES DEFENDED UNDER LAB LEADER’S SUPERVISION

Ł. Świech, A. Malik, M. Perycz, M. Urbańska, A. Skałecka, J. Lipka, A. Urbańska, M. Firkowska, K. Kisielewska, A. Kościelny.

Group members

Lab Leader
Jacek Jaworski, PhD, Professor

Senior Researchers
Ewa Liszewska, PhD
Małgorzata Urbańska, PhD

Postdoctoral Researchers
Roberto Pagano, PhD

Research Specialist
Katarzyna Machnicka, MSc
Katarzyna Durczyńska, MSc
Shiwani Kumari, PhD

PhD Students
Katarzyna Orzoł, MSc
Hemasri Kilaru, MSc 

Lab Technician
Alina Zielińska, BSc 

Laboratory Support Specialist:
Angelika Jocek, MSc

Volunteers
Julia Łukasiewicz
Gabriela Chmurzyńska
Wiktoria Kowalska
Karolina Protokowicz, PhD