We focus on the mechanisms of protein metabolism - maintenance of the balance between the synthesis and degradation of proteins. We explore the regulation of translation, ubiquitin-proteasome system, chaperone network, and muscular exophers in proteostasis. However, we are sometimes intrigued by topics outside this list. In our laboratory, we use a combination of biochemical, microscopic, molecular genetics, and bioinformatics techniques, supported by mammalian cell assays and the nematode Caenorhabditis elegans.

Our research

Cellular adaptation to cold

1

To counteract cold, organisms developed various types of responses, ranging from cold avoidance to adaptation. The latter strategy is used by hibernating animals, which, in extreme cases, can survive subzero temperatures for many days. We focus on deciphering mechanisms altering the abundance and types of cellular messenger RNAs and proteins, as these kinds of molecules are critical for the live-or-die decision of the cell. As in some disease states, like stroke, cooling can facilitate a patient's recovery, understanding how cells adapt to cold has the potential to influence treatments of human disorders.

 

Mechanisms of muscular exopheresis

2

We discovered that large extracellular vesicles, termed exophers, that attribute in neurons and cardiomyocytes and carry damaged subcellular components, are released by muscles to support embryonic growth in Caenorhabditis elegans. Our results demonstrate that an exopher formation (exopheresis) represents a transgenerational metabolic/resource management system that supports embryos in utero. Currently, we investigate the mechanism of exopher formation and the regulation of exopheresis at the molecular level. 

 

Stress-induced myosin folding and assembly mechanisms

3

Little is known about the regulation of muscle-specific response programs that coordinate protein quality control upon mechanical stress and in human disease. We established a Caenorhabditis elegans-centered array of experimental approaches for the in-depth investigation of myosin-directed stress induction mechanisms. The long-term objective of this project is to understand how protein folding and degradation networks are coordinated with the dynamics of myosin assembly, muscle integrity, and repair in the context of mechanical stress. 

 

E3 ligase complexes in the integration of proteostasis and aging

4new

 

From their synthesis to destruction, the fate of eukaryotic proteins is supervised by the ubiquitin-proteasome system (UPS). Cooperation of E3 ligases, essential components of the UPS that recognize damaged or misfolded proteins, can lead to the formation of alternative ubiquitylation structures that aid in directing substrate specificity. We investigate how specific E3 ligase pairs determine substrate recruitment and ubiquitin chain formation to coordinate proteolytic networks. Understanding the function and identifying the signals that coordinate the interaction between E3 ligases will provide information on how proteolytic networks are tuned to maintain cellular proteostasis in health and disease.

 

The regulation of methionine metabolism by the ubiquitin-proteasome system

5new

 

Methylation is the modification that various cellular molecules, from nucleic acids to proteins to lipids, undergo. It is central to the regulation of many biological processes, including gene expression, signaling, protein synthesis and lipid metabolism. The long-term goal of this project is to understand how the ubiquitin-proteasome system modulates cellular methylation potential. Congenital methylation disorders are a group of rarely described and probably largely unrecognized disorders involving transmethylation processes. We model these human diseases on Caenorhabditis elegans to understand the molecular basis involved in the dysfunction of methylation pathway enzymes and their impact on physiology.

wpokrzywa

Wojciech Pokrzywa, PhD, DSc Habil 

Correspondence address:
Laboratory of Protein Metabolism 
International Institute of Molecular and Cell Biology in Warsaw
4 Ks. Trojdena Street, 02-109 Warsaw, Poland
Email: This email address is being protected from spambots. You need JavaScript enabled to view it. |
www: pokrzywalab.com
tel: +48 (22) 597 0742; fax: +48 (22) 597 0715

DEGREES:

2020 - DSc Habil in Biological Sciences, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Poland
2009 - PhD in Biological Engineering and Agronomic Sciences at the Institute of Life Sciences, Molecular Physiology Group (FYMO), Catholic University of Louvain, Belgium.
2006 - Master of Advanced Science in Biological Engineering and Agronomic Sciences at the Catholic University of Louvain, Belgium.
2004 - Master’s in Microbiology at the University of Wroclaw, Poland.

PROFESSIONAL EXPERIENCE

2017 - present - Professor, Head of Laboratory of Protein Metabolism, International Institute of Molecular and Cell Biology in Warsaw, Poland
2009 - 2017 - Postdoctoral fellow at the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany.
2004 - 2008 - PhD studies at the Institute of Life Sciences, Molecular Physiology Group (FYMO), Catholic University of Louvain, Belgium.

HONORS, PRIZES AND AWARDS

2022 - SONATA BIS, National Science Center
2020 -
GRIEG, National Science Center
2018 - FIRST TEAM, Foundation for Polish Science
2018 - EMBO Installation Grant
2017 - OPUS, National Science Centre
2005 - PhD Fellowship from the FNRS-Fund for Scientific Research, Belgium
2004 - ERASMUS Scholarship

PokrzywaLab

Lab Leader:

  • Wojciech Pokrzywa, PhD, DSc Habil

Senior Researcher:

  • Małgorzata Piechota, PhD

Postdoctoral Researchers:

  • Abhishek Dubey, PhD

Research Technician:

  • Lilia Biriczova, M.Sc

  • Konrad Kowalski, M.Sc

Graduate Students:

  • Katarzyna Banasiak, M.Sc

  • Aniruddha Das, M.Sc

  • Pratik Kumar Mandal, M.Sc

  • Pankaj Thapa, M.Sc

  • Anwesha Sarkar, M.Sc

  • Natalia Szulc, M.Sc

Laboratory Support Specialists:

  • Anna Grabowska, PhD

  • Marta Niklewicz, M.Sc

2022

CHIP ubiquitin ligase is involved in the nucleolar stress management.

Piechota M, Biriczova L, Kowalski K, Szulc NA, Pokrzywa W.

bioRxiv preprint. 2022

DEGRONOPEDIA - a web server for proteome-wide inspection of degrons.

Szulc NA, Stefaniak F, Piechota M, Cappannini A, Bujnicki JM, Pokrzywa W.

bioRxiv preprint. 2022

Ferritin-mediated iron detoxification promotes hypothermia survival in Caenorhabditis elegans and murine neurons.

Pekec T, Lewandowski J, Komur AA, Sobańska D, Guo Y, Świtońska-Kurkowska K, Małecki JM, Dubey AA, Pokrzywa W, Frankowski M, Figiel M, Ciosk R.

Nat Commun.. 2022

A Dimer-Monomer Switch Controls CHIP-Dependent Substrate Ubiquitylation and Processing.

Balaji V, Müller L, Lorenz R, Kevei É, Zhang WH, Santiago U, Gebauer J, Llamas E, Vilchez D, Camacho CJ, Pokrzywa W, Hoppe T.

Mol Cell.. 2022

A novel de novo FEM1C variant is linked to neurodevelopmental disorder with absent speech, pyramidal signs, and limb ataxia.

Dubey AA, Krygier M, Szulc NA, Rutkowska K, Kosińska J, Pollak A, Rydzanicz M, Kmieć T, Mazurkiewicz-Bełdzińska M, Pokrzywa W, Płoski R.

Human Molecular Genetics. 2022

A heterotypic assembly mechanism regulates CHIP E3 ligase activity.

Das A, Thapa P, Santiago U, Shanmugam N, Banasiak K, Dabrowska K, Nolte H, Szulc NA, Gathungu RM, Cysewski D, Krüger M, Dadlez M, Nowotny M, Camacho CJ, Hoppe T, Pokrzywa W.

EMBO J. . 2022

Impaired iron recycling from erythrocytes is an early hallmark of aging.

Slusarczyk P, Mandal PK, Zurawska G, Niklewicz M, Chouhan KK, Macias M, Szybinska A, Cybulska M, Krawczyk O, Herman S, Mikula M, Serwa R, Lenartowicz M, Pokrzywa W, Mleczko-Sanecka K.

bioRxiv preprint. 2022

2021

The Dose-Dependent Pleiotropic Effects of the UBB+1 Ubiquitin Mutant.

Banasiak K, Szulc NA, Pokrzywa W.

Front. Mol. Biosci. . 2021

Muscle-derived exophers promote reproductive fitness.

Turek M, Banasiak K, Piechota M, Shanmugam N, Macias M, Śliwińska MA, Niklewicz M, Kowalski K, Nowak N, Chacinska A, Pokrzywa W.

EMBO Rep.. 2021

Maintaining proteostasis under mechanical stress.

Höhfeld J, Benzing T, Bloch W, Fürst DO, Gehlert S, Hesse M, Hoffmann B, Hoppe T, Huesgen PF, Köhn M, Kolanus W, Merkel R, Niessen CM, Pokrzywa W, Rinschen MM, Wachten D, Warscheid B.

EMBO Rep.. 2021

2020

Ubiquitin Signaling Regulates RNA Biogenesis, Processing, and Metabolism.

Thapa P, Shanmugam N, Pokrzywa W.

BioEssays. 2020

Article BioShell 3.0: Library for Processing Structural Biology Data.

Macnar JM, Szulc N, Kryś JD, Badaczewska-Dawid AE, Gront D.

Biomolecules. 2020

The ubiquitin-conjugating enzyme UBE2K determines neurogenic potential through histone H3 in human embryonic stem cells.

Fatima A, Irmak D, Noormohammadi A, Rinschen MM, Das A, Leidecker O, Schindler C, Sánchez-Gaya V, Wagle P, Pokrzywa W, Hoppe T, Rada-Iglesias A, Vilchez D.

Commun Biol.. 2020

Nutritional status and fecundity are synchronised by muscular exopheresis.

Turek M, Piechota M, Shanmugam N, Niklewicz M, Kowalski K, Chacińska A, Pokrzywa W.

bioRxiv. 2020

CHIP ubiquitylates NOXA and induces its lysosomal degradation in response to DNA damage.

Albert M-C, Brinkmann K, Pokrzywa W, Günther SD, Krönke M, Hoppe T, Kashkar H.

Cell Death & Disease. 2020

2018

The ubiquitin ligase UBR5 suppresses proteostasis collapse in pluripotent stem cells from Huntington's disease patients.

Koyuncu S, Saez I, Lee HJ, Gutierrez-Garcia R, Pokrzywa W, Fatima A, Hoppe T, Vilchez D.

Nat Commun.. 2018

Ubiquitylation Pathways In Insulin Signaling and Organismal Homeostasis.

Balaji V, Pokrzywa W, Hoppe T.

Bioessays. 2018

2017

Repair or Destruction: An Intimate Liaison Between Ubiquitin Ligases and Molecular Chaperones in Proteostasis

Kevei É, Pokrzywa W, Hoppe T

FEBS Lett. doi:10.1002/1873-3468.12750.. 2017

Chaperone-directed ubiquitylation maintains proteostasis at the expense of longevity.

Pokrzywa W, Lorenz R, Hoppe T

Worm. 2017

CHIPped balance of proteostasis and longevity.

Pokrzywa W, Hoppe T.

Oncotarget. 2017