Laboratory of Experimental and Clinical Neurosurgery

Head
prof. Ewa Koźniewska-Kołodziejska, PhD, MSc; phone: + 48 22 60 86 489, This email address is being protected from spambots. You need JavaScript enabled to view it.

Research staff
Marta Aleksandrowicz, PhD, MSc; phone: +48 22 60 86 566, +48 22 60 86 424, This email address is being protected from spambots. You need JavaScript enabled to view it.
Żanna Pastuszak-Stępień, MD, PhD; phone: +48 22 60 86 566, This email address is being protected from spambots. You need JavaScript enabled to view it.

Technical staff
Łukasz Przykaza, MSc; phone: +48 22 60 86 423, +48 22 60 86 596, This email address is being protected from spambots. You need JavaScript enabled to view it.

Research profile
• Disturbances of cerebral circulation following experimental ischemia and reperfusion.
• Pharmacological protection of the brain and cerebral blood vessels against transient ischemia/reperfusion damage
• Effect of high sodium diet and sodium-dependent hypertension on the regulation of the peripheral and cerebral resistance vessels
• Impairment of the regulation of cerebral vessels and brain function in experimental hyponatremia
• Analysis of the disturbances of intracranial pressure-volume relation in patients
• Differential diagnostics of normal pressure hydrocephalus and brain atrophy
• Effect of transcranial magnetic stimulation on blood supply and activity of the cerebral cortex in patients in acute stage of ischemic stroke

Grants

• "Searching for the background underlying the neuroprotective effects of the specific agonist of Y2 receptors - NPY(13-36) in the model of transient, focal cerebral ischemia in rats".”, nr 2019/33/N/NZ47/02894, Łukasz Przykaza, 2020 -2022.
• “Impact of vascular component and component related to cerebrospinal fluid circulation on the brain compliance”, 2016/23/N/ST7/01364, Katarzyna Kaczmarska, 2017-2019.
• „Effect of acute hyponatremia associated with vasopressin on the tone of the penetrating arterioles and the middle cerebral artery of the rat”, 2017/01/X/N24/016022017 , Marta Aleksandrowicz, 2017-2018

Collaboration
domestic
• Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw
• Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw
• Department of Neurology, Military Medical Institute, Warsaw
• Department of Neurobiology, Institute of Pharmacology PAS, Krakow
• Laboratory of Animal Models, Nencki Institute of Experimental Biology PAS, Warsaw
• Laboratory of Biomedical Optics, Nalecz Institute of Biocybernetics and Biomedical Engineering PAS, Warsaw
• Department of Neurosurgery, Medical Faculty, Medical University of Warsaw, Warsaw
• Department of Physics of Nanostructures and Nanotechnology, institute of Physics, Jagiellonian University, Krakow
foreign
• Department of Clinical Neurosciences University of Cambridge, Cambridge, UK.

Research equipment
• Two-channels laser-Doppler flowmeter (MOOR Instruments DRT4) with data acquisition station
• Setup for isolated blood vessels studies (Olympus inverted microscope, Masterflex, peristaltic pump, organ chamber)
• Gas anaesthesia system for small animals (Stoelting)
• Small animals respirator (Harvard Apparatus)
• Programmable syringe infusion pump (Harvard Apparatus)
• Blood pressure gauge (Statham-Gould)
• Homeothermic blanket system (Harvard Apparatus)
• Transcranial Doppler (Sonomed)
• Intraoperative ultrasonography with microprobe (Sonomed)
• Posturography platform

Research methods
• Measurement of microflow in cerebral cortex
• Assessment of the reactivity of isolated blood vessels
• Assessment of the neurovascular coupling
• Behavioural tests
• Lumbar infusion test
• Instrumental assessment of gait, posturography
• Noninvasive estimation of cerebral perfusion and metabolism in humans

Selected publications

• Aleksandrowicz M, Kozniewska E. Compromised regulation of the rat brain parenchymal arterioles in vasopressin-associated acute hyponatremia. Microcirculation. 2020 Jun 30. DOI: 10.1111/micc.12644.
• Uryga A, Kaczmarska K, Burzyńska M, Czosnyka M, Kasprowicz M. A comparison of the time constant of the cerebral arterial bed using invasive and non-invasive arterial blood pressure measurements. Physiol Meas. 2020 Jun 11. DOI: 10.1088/1361-6579/ab9bb6.
• Kaczmarska K, Uryga A, Placek MM, Calviello L, Kasprowicz M, Varsos GV, Czosnyka Z, Koźniewska E, Sierzputowski T, Koszewski W, Czosnyka M. Critical closing pressure during experimental intracranial hypertension: comparison of three calculation methods. Neurol Res. 2020;42(5):387-397. DOI: 10.1080/01616412.2020.1733323.
• Onyszkiewicz M, Gawrys-Kopczynska M, Sałagaj M, Aleksandrowicz M, Sawicka A, Koźniewska E, Samborowska E, Ufnal M. Valeric acid lowers arterial blood pressure in rats. Eur J Pharmacol. 2020; 877:173086. DOI: 10.1016/j.ejphar.2020.173086.
• Aleksandrowicz M, Klapczynska K, Kozniewska E. Dysfunction of the endothelium and constriction of the isolated rat's middle cerebral artery in low sodium environment in the presence of vasopressin. Clin Exp Pharmacol Physiol. 2020;47(5):759-764. DOI: 10.1111/1440-1681.13242.
• Onyszkiewicz M, Gawrys-Kopczynska M, Konopelski P, Aleksandrowicz M, Sawicka A, Koźniewska E, Samborowska E, Ufnal M. Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon- vagus nerve signaling and GPR41/43 receptors. Pflugers Arch. 2019; 471(11-12):1441-1453. DOI: 10.1007/s00424-019-02322-y
• Bejm K, Wojtkiewicz S, Sawosz P, Perdziak M, Pastuszak Ż, Sudakou A, Guchek P, Liebert A. Influence of contrast-reversing frequency on the amplitude and spatial distribution of visual cortex hemodynamic responses. Biomed Optic Express. 2019; 12:6296-6312. DOI: 10.1364/BOE.10.006296.
• Uryga A, Kasprowicz M, Calviello L, Diehl RR, Kaczmarska K, Czosnyka M. Assessment of cerebral hemodynamic parameters using pulsatile versus non-pulsatile cerebral blood outflow models. J Clin Monit Comput. 2019, 33(1):85-94. DOI: 10.1007/s10877-018-0136-1.
• Uryga A, Kasprowicz M, Burzynska M, Calviello L, Kaczmarska K, Czosnyka M. Cerebral arterial time constant calculated from the middle and posterior cerebral arteries in healthy subjects. J Clin Monit Comput. 2019, 33 (4): 605-613. DOI: 10.1007/s10877-018-0207-3.
• Czarnecka A, Aleksandrowicz M, Jasiński K, Jaźwiec R, Kalita K, Hilgier W, Zielińska M. Cerebrovascular reactivity and cerebral perfusion of rats with acute liver failure: role of L-glutamine and asymmetric dimethylarginine in L-arginine-induced response. J Neurochem. 2018; 147(5):692-704. DOI: 10.1111/jnc.14578.
• Motyl J, Przykaza L, Boguszewski PM, Kosson P, Strosznajder JB. Pramipexole and Fingolimod exert neuroprotection in a mouse model of Parkinson's disease by activation of sphingosine kinase 1 and Akt kinase. Neuropharmacology. 2018, 135:139-150. DOI: 10.1016/j.neuropharm.2018.02.023.
• Domin H, Przykaza L, Kozniewska E, Boguszewski PM, Śmialowska M. Neuroprotective effect of the group III mGlu receptor agonist ACPT-I after ischemic stroke in rats with essential hypertension. Prog Neuropsychopharmacol Biol Psychiatry. 2018; 84 (Pt A): 93-101. DOI: 10.1016/j.pnpbp.2018.02.006.
• Aleksandrowicz M, Kozniewska E. Effect of vasopressin-induced chronic hyponatremia on the regulation of the middle cerebral artery of the rat. Pflugers Arch. 2018; 470 (7): 1047-1054. DOI: 10.1007/s00424-018-2141-0.
• Pastuszak Z, Stępień A, Kamiński G, Deptuła-Krawczyk E, Trawińska L, Kryszak A. Analysis of growth hormone levels in the blood of patients with drug resistant depression. Pol Arch Intern Med. 2018 ;128(4):263-265. DOI: 10.20452/pamw.4256.
• Pastuszak Ż, Koźniewska E, Stępień A, Piusińska-Macoch A, Czernicki Z, Koszewski W. Importance rating of risk factors of ischemic stroke in patients over 85 years old in the polish population. Neurol Neurochir Pol. 2018; 52(1):88-93 . DOI: 10.1016/j.pjnns.2017.11.007.
• Kaczmarska K, Kasprowicz M, Uryga A, Calviello L, Varsos G, Czosnyka Z, Czosnyka M. Critical closing pressure during controlled increase in intracranial pressure – Comparison of three methods. IEEE Trans Biomed Eng. 2018, 65(3):619-624. DOI: 10.1109/TBME.2017.2707547.
• Aleksandrowicz M, Dworakowska B, Dolowy K, Kozniewska E. Restoration of the response of the middle cerebral artery of the rat to acidosis in hyposmotic hyponatremia by the opener of large-conductance calcium sensitive potassium channels (BKCa). J Cereb Blood Flow Metab. 2017; 37 (9): 3219-3230. DOI: 10.1177/0271678X16685575.
• Domin H, Przykaza Ł, Jantas D, Kozniewska E, Boguszewski PM, Śmiałowska M. Neuropeptide Y Y2 and Y5 receptors as promising targets for neuroprotection in primary neurons exposed to oxygen-glucose deprivation and in transient focal cerebral ischemia in rats. Neuroscience. 2017, 344:305-325. DOI: 10.1016/j.neuroscience.2016.12.040.
• Domin H, Przykaza Ł, Jantas D, Kozniewska E, Boguszewski PM, Śmiałowska M. Neuroprotective potential of the group III mGlu receptor agonist ACPT-I in animal models of ischemic stroke: In vitro and in vivo studies. Neuropharmacology. 2016, 102:276-294. DOI: 10.1016/j.neuropharm.2015.11.025.

Laboratory of Molecular Basis of Neurodegeneration

Head
Michał Węgrzynowicz, PhD - phone: +48 22 608 64 05; email: This email address is being protected from spambots. You need JavaScript enabled to view it.   room C-301
Research staff
Aleksandra Owczarek, PhD - phone: +48 22 608 65 21; email: This email address is being protected from spambots. You need JavaScript enabled to view it. room C-303
PhD students
Aleksandra Duchnowska, MSc - phone: +48 22 608 65 21; email: This email address is being protected from spambots. You need JavaScript enabled to view it. 
Parisa Malakouti, MSc - phone +48 22 608 65 21; email: This email address is being protected from spambots. You need JavaScript enabled to view it.  room C-303
Martyna Nalepa, MSc Eng - phone: +48 22 608 65 21; email: This email address is being protected from spambots. You need JavaScript enabled to view it.  room C-303
Aleksandra Skweres, MSc - phone: +48 22 608 65 21; email: This email address is being protected from spambots. You need JavaScript enabled to view it. room C-303
Graduate students
Filip Suchożebski - phone: +48 22 608 65 21; email: This email address is being protected from spambots. You need JavaScript enabled to view it.   room C-303
Research profile
The Laboratory was set up in 2019. The studies carried out in the Laboratory are aimed at understanding the mechanisms responsible for neuronal dysfunction and death in different neurodegenerative diseases like Huntington's disease, Parkinson's disease, Alzheimer's disease and others. We are particularly interested in the causes and consequences of protein aggregation, a phenomenon considered as a fundamental factor in neurodegeneration. We would like to understand what are the common pathways in the pathogenesis of different neurodegenerative diseases, but also what constitutes the basis for clinical and neuropathological correlates specific for individual diseases. Why, in particular disease, given protein is prone to aggregate in specific cell type and not in the other. Why defined brain regions are exceptionally sensitive to the toxicity related to aggregation of specific protein, when other brain regions are protected. Is it related to the cell-autonomous factors (like intrinsic functional or molecular properties of the cell) or to external stimuli (like interactions within cellular microenvironment or anatomical and functional connections with other brain regions). We believe that answering these questions will help to develop novel, mechanism-based therapeutic strategies against currently incurable neurodegenerative diseases.

Grants
Role of arginase 2 in the function of the striatum and in the pathogenesis of Huntington's disease

• funding: National Science Centre, Sonata Bis grant 2018/30/E/NZ1/00144
• principal investigator: Michał Węgrzynowicz, PhD
• timeline: 2019-2025

Distribution and identification of hippocampal proteins undergoing posttranslational modifications with putrescine in hypoxia

• funding: National Science Centre, Miniatura grant
• principal investigator: Aleksandra Owczarek, PhD
• timeline: 2023-2024

Importance of polyamine metabolism compartmentation in hippocampus for differential sensitivity of CA1-CA3 regions to excitotoxicity; role of mitochondrial calcium homeostasis

• funding: Internal Research Fund, MMRI PAS, no. FBW-024
• principal investigator: Aleksandra Kaczyńska, MSc
• timeline: 2023-2024

Utilization of novel probe TvS-Put for identification of the proteins undergoing posttranslational modifications with putrescine in hippocampal region CA2 in mouse

• funding: Internal Research Fund, MMRI PAS, no. FBW-019
• principal investigator: Michał Węgrzynowicz, PhD
• timeline: 2021-2023

Domestic collaboration

• prof. Barbara Zabłocka, dr. Małgorzata Beręsewicz-Haller, Molecular Biology Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw
• dr. Remigiusz Serwa, Proteomics Core Facility, International Institute of Molecular Mechanisms and Machines, Polish Academy of Sciences, Warsaw
• dr. Emilia Samborowska, Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw
• prof. Agata Adamczyk, dr. Anna Wilkaniec, Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw
• dr. Katarzyna Winiarska, Department of Metabolic Regulation, Faculty of Biology, University of Warsaw
• prof. Magdalena Zielińska, Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw
• dr. Beata Toczyłowska, Laboratory of Diagnosis and Therapy Support of Metabolic Diseases, Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw
• dr. Karolina Szczepanowska, Laboratory of Metabolic Quality Control, International Institute of Molecular Mechanisms and Machines, Polish Academy of Sciences, Warsaw
• dr. Małgorzata Frontczak-Baniewicz, dr. Magdalena Gewartowska, Laboratory of Electron Microscopy, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw
• dr. Grzegorz Kreiner, Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Cracow

International collaboration

• prof. Maria Grazia Spillantini, PhD, Department of Clinical Neurosciences, University of Cambridge, UK
• dr. Giorgio Vivacqua, Faculty of Medicine and Surgery, Campus Biomedico University of Roma, Italy
• prof. Aaron Bowman, School of Health Sciences, Purdue University, West Lafayette, USA
• prof. Ricardo Borges, Department of Physical Medicine and Pharmacology, Pharmacology Unit, Medical School, University of La Laguna, Spain

Research equipment
• Fast cooling unit for microtomes, Slee Medical MTR
• Stereomicroscope, Nikon SMZ800N
• Centrifugal vacuum concentrator, Eppendorf Concentrator 5301

Research methods

• Employing transgenic animal models to study pathology of the Central Nervous System
• Organotypic cultures of rat hippocampus
• Studies employing acute brain slices
• Precise dissection of rodent CNS tissues
• High-sensitivity histological, immunohistochemical and immunofluorescence techniques
• Modelling pathological states (excitotoxicity, hypoxia) in vitro
• Experimental regulation of selected cellular pathways in vitro using pharmacological and genetic techniques
• Isolation of subcellular fractions from animal tissues
• Qualitative and quantitative microscopic analysis
• Real-time analysis of cellular/subcellular fluctuations of calcium and nitric oxide in vitro
• Imaging and biochemical analyses of protein posttranslational modifications using novel probes
• Click chemistry
• Measurements of metabolites in animal tissues
• Enzymatic activity measurements
• Immunodetection of proteins (western blot, dot blot, filter retardation assay)
• Protein aggregation analysis (fractionation, filtration, enzymatic digestion, fluorescence probes)
• Behavioural assessment of motor and cognitive functions in mice
• Stereotactic brain surgery (injections, implantations)
• Microdialysis
  

Selected publications

• Pawlik M, Czarnecka AM, Kołodziej M, Skowrońska K, Węgrzynowicz M, Podgajna M, Czuczwar SJ, Albrecht J (2023) Attenuation of initial pilocarpine-induced electrographic seizures by methionine sulfoximine pretreatment tightly correlates with the reduction of extracellular taurine in the hippocampus. Epilepsia. 64(5):1390-1402
• Vivacqua G, Mason M, De Bartolo MI, Węgrzynowicz M, Calò L, Belvisi D, Suppa A, Fabbrini G, Berardelli A, Spillantini M (2023) Salivary α-Synuclein RT-QuIC Correlates with Disease Severity in de novo Parkinson's Disease. Mov Disord. 38(1):153-155
• Levin J, Sing N, Melbourne S, Morgan A, Mariner C, Spillantini MG, Wegrzynowicz M, Dalley JW, Langer S, Ryazanov S, Leonov A, Griesinger C, Schmidt F, Weckbecker D, Prager K, Matthias T, Giese A (2022) Safety, tolerability and pharmacokinetics of the oligomer modulator anle138b with exposure levels sufficient for therapeutic efficacy in a murine Parkinson model: A randomised, double-blind, placebo-controlled phase 1a trial. EBioMedicine. 80:104021
• Grzywa TM, Sosnowska A, Rydzynska Z, Lazniewski M, Plewczynski D, Klicka K, Malecka-Gieldowska M, Rodziewicz-Lurzynska A, Ciepiela O, Justyniarska M, Pomper P, Grzybowski MM, Blaszczyk R, Wegrzynowicz M, Tomaszewska A, Basak G, Golab J, Nowis D (2021) Potent but transient immunosuppression of T-cells is a general feature of CD71+ erythroid cells. Commun Biol. 4(1):1384
• Caló L, Hidari E, Wegrzynowicz M, Dalley JW, Schneider BL, Podgajna M, Anichtchik O, Carlson E, Klenerman D, Spillantini MG (2021) CSPα reduces aggregates and rescues striatal dopamine release in α-synuclein transgenic mice. Brain. 144(6):1661-1669
• Migdalska‐Richards A*, Wegrzynowicz M*, Harrison IF, Verona G, Bellotti V, Spillantini MG, Schapira AHV (2020) L444P Gba1 mutation increases formation and spread of α-synuclein deposits in mice injected with mouse α-synuclein pre-formed fibrils. PLoS One. 15(8):e0238075

Prior publications of the Laboratory members:

• Owczarek A, Gieczewska KB, Jarzyna R, Frydzinska Z, Winiarska K (2021) Transcription Factor ChREBP Mediates High Glucose-Evoked Increase in HIF-1α Content in Epithelial Cells of Renal Proximal Tubules. Int J Mol Sci. 22(24):13299
• Owczarek A, Gieczewska KB, Polanska M, Paterczyk B, Gruza A, Winiarska K. (2021) Melatonin Lowers HIF-1α Content in Human Proximal Tubular Cells (HK-2) Due to Preventing Its Deacetylation by Sirtuin 1. Front Physiol. 11:572911
• Owczarek A, Gieczewska K, Jarzyna R, Jagielski AK, Kiersztan A, Gruza A, Winiarska K (2020) Hypoxia increases the rate of renal gluconeogenesis via hypoxia-inducible factor-1-dependent activation of phosphoenolpyruvate carboxykinase expression. Biochimie. 171-172:31-37
• Wegrzynowicz M, Bar-On D, Calo' L, Anichtchik O, Iovino M, Xia J, Ryazanov S, Leonov A, Giese A, Dalley JW, Griesinger C, Ashery U, Spillantini MG (2019) Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model. Acta Neuropathol. 138(4):575-595
• Migdalska-Richards A, Wegrzynowicz M, Rusconi R, Deangeli G, Di Monte DA, Spillantini MG, Schapira AHV (2017) The L444P Gba1 mutation enhances alpha-synuclein induced loss of nigral dopaminergic neurons in mice. Brain. 140(10):2706-2721
• Bichell TJV*, Wegrzynowicz M*, Tipps KG, Bradley EM, Uhouse MA, Bryan M, Horning K, Fisher N, Dudek K, Halbesma T, Umashanker P, Stubbs AD, Holt HK, Kwakye GF, Tidball AM, Colbran RJ, Aschner M, Neely MD, Di Pardo A, Maglione V, Osmand A, Bowman AB (2017) Reduced bioavailable manganese causes striatal urea cycle pathology in Huntington's disease mouse model. Biochim Biophys Acta Mol Basis Dis. 1863(6):1596-1604
• Calo L, Wegrzynowicz M, Santivañez-Perez J, Grazia Spillantini M (2016) Synaptic failure and α-synuclein. Mov Disord. 31(2):169-77
• Tozzi A, de Iure A, Bagetta V, Tantucci M, Durante V, Quiroga-Varela A, Costa C, Di Filippo M, Ghiglieri V, Latagliata EC, Wegrzynowicz M, Decressac M, Giampà C, Dalley JW, Xia J, Gardoni F, Mellone M, El-Agnaf OM, Ardah MT, Puglisi-Allegra S, Björklund A, Spillantini MG, Picconi B, Calabresi P (2016) Alpha-Synuclein Produces Early Behavioral Alterations via Striatal Cholinergic Synaptic Dysfunction by Interacting With GluN2D N-Methyl-D-Aspartate Receptor Subunit. Biol Psychiatry. 79(5):402-414
• Winiarska K, Dzik JM, Labudda M, Focht D, Sierakowski B, Owczarek A, Komorowski L, Bielecki W (2016) Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase. J Pineal Res. 60(1):109-117
• Wegrzynowicz M*, Bichell TJ*, Soares BD, Loth MK, McGlothan JS, Mori S, Alikhan FS, Hua K, Coughlin JM, Holt HK, Jetter CS, Pomper MG, Osmand AP, Guilarte TR, Bowman AB (2015) Novel BAC Mouse Model of Huntington's Disease with 225 CAG Repeats Exhibits an Early Widespread and Stable Degenerative Phenotype. J Huntingtons Dis. 4(1):17-36.
• Wegrzynowicz M, Holt HK, Friedman DB, Bowman AB (2012) Changes in the striatal proteome of YAC128Q mice exhibit gene-environment interactions between mutant huntingtin and manganese. J Proteome Res. 11(2):1118-3
• Williams BB, Li D, Wegrzynowicz M, Vadodaria BK, Anderson JG, Kwakye GF, Aschner M, Erikson KM, Bowman AB (2010) Disease-toxicant screen reveals a neuroprotective interaction between Huntington's disease and manganese exposure J Neurochem. 112(1):227-3

 

Laboratory of human disease multiomics

Laboratories B517-B520

Head
Dawid Walerych PhD Hab., phone: +48 22 60 86 641, This email address is being protected from spambots. You need JavaScript enabled to view it.

Research staff
Maria Grześ PhD, phone: +48 22 60 86 641, This email address is being protected from spambots. You need JavaScript enabled to view it.
Magdalena Oroń PhD, phone: +48 22 60 86 641, This email address is being protected from spambots. You need JavaScript enabled to view it.
Qais Ahmad Naseer, PhD, phone: +48 22 60 86 641, This email address is being protected from spambots. You need JavaScript enabled to view it. 

PhD students
Akanksha Jaiswar MSc Eng. (bioinformatics), phone: +48 22 60 86 641, This email address is being protected from spambots. You need JavaScript enabled to view it.
Luca Gazzola MSc, phone: +48 22 60 86 641, This email address is being protected from spambots. You need JavaScript enabled to view it.
Marcin Grochowski MSc, phone: +48 22 60 86 641, This email address is being protected from spambots. You need JavaScript enabled to view it.

Undergraduate students
Justyna Legierska, phone: +48 22 60 86 641

Research profile
• Understanding molecular processes leading to human diseases, by using molecular large-scale analyses.
• Molecular programs of driver oncogenes in human neoplasias (mutant TP53, K/H/N-RAS, EGFR, PI3KCA, hyperactive C/N-MYC, CTNNB1, HSP90/HSP70/HSP4, the cellular proteasome machinery).
• Using a variety of large-scale omics methods (e.g. transcriptomics and proteomics) in conjunction with low-scale validation methods – leading to uncovering functional mechanisms of molecular pathways driven by the oncogenes and possibilities of exploiting them therapeutically in pre-clinical drug tests in human cancer models.

Grants

• „Influence of oligmierization ononcogenic activity of p53 mutant variants”, Miniatura NCN 2017/01/X/NZ3/01772, manager Dawid Walerych, 01-12.2018
• „Identification of the proteasome machinery targets in human cancer”, Marie-Curie Individual Fellowship Komisji Europejskiej H2020/795441, manager Dawid Walerych, 2018-2020
• „Proteomic identification and therapeutic use of the proteasome machinery targets in human cancer”, Opus NCN 2017/25/B/NZ5/01343, manager Dawid Walerych, 2018-2021
•  „Multi-onco-map: a multi-omic map of major oncogene function in cancer”, Sonata Bis NCN 2017/26/E/NZ5/00663, manager Dawid Walerych, 2018-2022

Collaboration
domestic
• Central Clinical Hospital of Ministry of Interior and Administration, Warsaw
• National Center of Oncology, Warsaw
• Warsaw Medical University, Warsaw

foreign
• Max Planck Institute of Biochemistry, Martinsired, Germany
• ICEGB institute and University of Trieste, Italy

Research equipment
• Diagenode Sonicator
• Lumistar Galaxy Luminometer
• Electronic cell router Countess II

Research methods

• Obtaining, analysis and overlap of multi-omics data (genomics, transcriptomics, proteomics and metabolomics)
• Functional molecular in vitro research on oncogenes and molecular reprogramming of cancer cells – using genetics (e.g. CRISPR-Cas9), biochemistry and cell biology
• Research on phenotypes of cells undergoing genetic manipulation or drug treatment in vitro – viability, migration, invasion, 2D/3D colony formation, 3D growth, organotypic structure formation, angiogenesis
• Establishing and analysis of cancer patient material bio-bank (tumors, healthy tissue margins, blood samples) for use in validation and association studies
• Establishing and use tumor-derived organoid cultures
• Testing of anti-tumor therapeutic methods in vitro (cell lines, organoids) and in vivo (cell line- and organoid-derived xenografts).

Selected publications

• Grzes, M., Oron, M., Staszczak, Z., Jaiswar, A., Nowak-Niezgoda, M., and Walerych, D.* (2020). A Driver Never Works Alone-Interplay Networks of Mutant p53, MYC, RAS, and Other Universal Oncogenic Drivers in Human Cancer. Cancers 12, (2020).
• Walerych D*, Pruszko M, Zyla L, Wezyk M, Gaweda-Walerych K, Zylicz A. Wild-type p53 oligomerizes more efficiently than p53 hot-spot mutants and overcomes mutant p53 gain-of-function via a “dominant-positive” mechanism. Oncotarget. 9: 32063-80, (2018).
• Lisek, K., Campaner, E., Ciani, Y., Walerych, D.* & Del Sal, G.* Mutant p53 tunes the Nrf2-dependent antioxidant response to support survival of cancer cells. Oncotarget 9, 20508-20523, (2018).
  Selected earlier publications of laboratory employees, since 2016:
• Visone, R., Bacalini, M. G., Di Franco, S., Ferracin, M., Colorito, M. L., Pagotto, S., Laprovitera, N., Licastro, D., Di Marco, M., Scavo, E., Grzes M., et al. (2019). DNA methylation of shelf, shore and open sea CpG positions distinguish high microsatellite instability from low or stable microsatellite status colon cancer stem cells. Epigenomics 11, 587-604, (2019).
• Laprovitera N, Grzes M, Porcellini E, Ferracin M. Cancer Site-Specific Multiple microRNA Quantification by Droplet Digital PCR. Front Oncol. 15 (8):447, (2018)
• Donzelli S, Milano E, Puszko M, Sacconi A, Masciarelli S, Iosue I, Melucci E, Gallo E, Terrenato I, Mottolese M, Zylicz M, Zylicz A, Fazi F, Blandino G, Fontemaggi G. Expression of ID4 protein in breast cancer cells induces reprogramming of tumour-associated macrophages. Breast Cancer Res. 20(1):59, (2018).
• Pruszko, M., Milano, E., Zylicz, A., Zylicz, M., Blandino, G. & Fontemaggi, G. Zebrafish as experimental model to establish the contribution of mutant p53 and ID4 to breast cancer angiogenesis in vivo. J Thorac Dis 10, E231-E233, (2018).
• Mantovani, F., Walerych, D. & Sal, G. D. Targeting mutant p53 in cancer: a long road to precision therapy. FEBS J 284, 837-850, (2017).
• Tosi, A., Dalla Santa, S., Cappuzzello, E., Marotta, C., Walerych, D., Del Sal, G., Zanovello, P., Sommaggio, R. & Rosato, A. Identification of a HLA-A*0201-restricted immunogenic epitope from the universal tumor antigen DEPDC1. Oncoimmunology 6, e1313371, (2017).
• Pruszko, M., Milano, E., Forcato, M., Donzelli, S., Ganci, F., Di Agostino, S., De Panfilis, S., Fazi, F., Bates, D. O., Bicciato, S., Zylicz, M., Zylicz, A., Blandino, G. & Fontemaggi, G. The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1. EMBO Rep 18, 1331-1351, (2017).
• Garibaldi, F., Falcone, E., Trisciuoglio, D., Colombo, T., Lisek, K., Walerych, D., Del Sal, G., Paci, P., Bossi, G., Piaggio, G. & Gurtner, A. Mutant p53 inhibits miRNA biogenesis by interfering with the microprocessor complex. Oncogene 35, 3760-3770, (2016).
• Walerych, D., Lisek, K., Sommaggio, R., Piazza, S., Ciani, Y., Dalla, E., Rajkowska, K., Gaweda-Walerych, K., Ingallina, E., Tonelli, C., Morelli, M. J., Amato, A., Eterno, V., Zambelli, A., Rosato, A., Amati, B., Wisniewski, J. R. & Del Sal, G. Proteasome machinery is instrumental in a common gain-of-function program of the p53 missense mutants in cancer. Nat Cell Biol 18, 897-909, (2016).

Tumor Microenvironment Laboratory

Head
Dr hab. Agnieszka Bronisz - phone: +48 22 60 86 567, This email address is being protected from spambots. You need JavaScript enabled to view it.

Project manager / Administration
dr n. biol. Elżbieta Lewandowska-Gnatowska - phone +48 22 60 86 502; This email address is being protected from spambots. You need JavaScript enabled to view it.

PhD students
Mgr Klaudia Kiel - phone +48 22 60 86 419; This email address is being protected from spambots. You need JavaScript enabled to view it.
Mgr Arpita Balakrishnan - phone +48 22 60 86 419; This email address is being protected from spambots. You need JavaScript enabled to view it.

Former Lab Members
dr Kamil Krawczyński; phone 22 60 86 419

Research profile
• Study of the microenvironment – the cancer niche, especially microenvironment of glioblastoma (GBM), and glioblastoma stem-like cell GSC cells that are to be instrumental initiating the formation of this cancer
• Understanding the mechanisms of direct and indirect interactions of the microenvironment with cancer cells
• The impact of interactions between cancer cells and tumor microenvironment on molecular mechanisms conducted in the cell, especially on changes in the regulation of gene expression through non-coding RNA (ncRNA)

Grants

• The role of non-coding RNA in the modification of epigenetic tumorigenesis mechanisms
  Agnieszka Bronisz: National Science Centre Poland, grant Opus 15, nr 2018/29/B/NZ1/01016, 2019-2023
• Extracellular vesicles modified ex vivo as an anti-cancer immune-response boosting vaccine.
  Klaudia Kiel, NCN Pl, Preludium 20, 2021/41/N/NZ6/02682, 2022-2025.
• Inducing death in glioblastoma: Targeting ferroptosis-related genes in glioblastoma stem-like cells as a potential therapeutic approach. 
  Kamil Krawczyński, IMDIK FBW 003-005; 2022-2023 
• Extracellular vesicles modified ex vivo as an anti-cancer immune-response boosting vaccine.
  Agnieszka Bronisz. IMDiK FBW 001-001;2021-2022

Collaboration
domestic
• Dr. Elżbieta Salińska / Mossakowski Medical Center/ Warszawa, Polska
foreign
• Dr E. Antonio Chiocca / Brigham and Women’s Hospital / Boston, MA, USA
• Dr Ralph Weissleder / Massachusetts General Hospital / Boston, MA, USA
• Dr Hiroshi Nakashima / Harvard Medical School / Boston, MA, USA
• Dr Franz Ricklefs / Medical Center Hamburg-Eppendorf / Hamburg, Germany
• Dr Mariano Viapiano / SUNY Upstate Medical University / Syracuse, NY, USA
• Dr Benjamin Purow / University of Virginia / Charlottesville, VA, USA

Research methods
• Proteomics (WB, IF, IHC, Masspectroskopy)
• Genomics (qPCR, Gene Arrays, NGS)
• Cellular models (3D cultures)
• Animal models (intracranial xenografts)
• Genetic engineering (siRNA, shRNA, CRISPR/Cas9, lentivirus)
• Therapeutic carriers (nanoparticles, oncolytic viruses, extracellular vesicles)

Patents and patent applications
US Patent App. 18/031,054 ; 2023; Godlewski J, Bronisz A, EA Chiocca EA Compositions and Methods Targeting circ2082 for the Treatment of Cancer

Selected publications

• Kiel K, Król SK, Bronisz A, Godlewski J. MiR-128-3p - a gray eminence of the human central nervous system. Mol Ther Nucleic Acids. 2024 Feb 6;35(1):102141. doi: 10.1016/j.omtn.2024.102141. PMID: 38419943; PMCID: PMC10899074. https://pubmed.ncbi.nlm.nih.gov/38419943/
• Szczepaniak A, Bronisz A, Godlewski J. Circular RNAs-New Kids on the Block in Cancer Pathophysiology and Management. Cells. 2023 Feb 8;12(4):552. doi: 10.3390/cells12040552. PMID: 36831219; PMCID: PMC9953808.  https://pub>med.ncbi.nlm.nih.gov/3683121
• Bronisz A, Rooj AK, Krawczyński K, Peruzzi P, Salińska E, Nakano I, Purow B, Chiocca EA, Godlewski J. The nuclear DICER-circular RNA complex drives the deregulation of the glioblastoma cell microRNAome. Sci Adv. 2020 Dec 16;6(51):eabc0221. PMID:33328224
• Godlewski J, Farhath M, Ricklefs FL, Passaro C, Kiel K, Nakashima H, Chiocca EA, Bronisz A. Oncolytic Virus Therapy Alters the Secretome of Targeted Glioblastoma Cells. Cancers (Basel). 2021;13(6):1287. PMID: 33799381
• Kitamura Y, Kanaya N, Moleirinho S, Du W, Reinshagen C, Attia N, Bronisz A, Revai Lechtich E, Sasaki H, Mora JL, Brastianos PK, Falcone JL, Hofer AM, Franco A, Shah K,. Anti-EGFR VHH-armed death receptor ligand-engineered allogeneic stem cells have therapeutic efficacy in diverse brain metastatic breast cancers. Sci Adv. 2021 Mar 3;7(10):eabe8671.PMID: 3365
• Krawczynski K, Godlewski J, Bronisz A. Oxidative Stress-Part of the Solution or Part of the Problem in the Hypoxic Environment of a Brain Tumor. Antioxidants (Basel). 2020 Aug 14;9(8):747. PMID: 32823815
• Bronisz A, Salinska E, Chiocca EA, Godlewski J. Hypoxic Roadmap of Glioblastoma-Learning about Directions and Distances in the Brain Tumor Environment. Cancers (Basel). 2020 May 13; 12(5). PMID: 32413951
• Ogawa D, Ansari K, Nowicki MO, Salinska E, Bronisz A, Godlewski J. MicroRNA-451 Inhibits Migration of Glioblastoma while Making It More Susceptible to Conventional Therapy. Noncoding RNA. 2019 Mar 15; 5(1). PMID: 30875963
• Bhaskaran V, Nowicki MO, Idriss M, Jimenez MA, Lugli G, Hayes JL, Mahmoud AB, Zane RE, Passaro C, Ligon KL, Haas-Kogan D, Bronisz A, Godlewski J, Lawler SE, Chiocca EA, Peruzzi P. The functional synergism of microRNA clustering provides therapeutically relevant epigenetic interference in glioblastoma. Nat Commun. 2019 01 25; 10(1):442. PMID: 30683859
• Jun HJ, Appleman VA, Wu HJ, Rose CM, Pineda JJ, Yeo AT, Delcuze B, Lee C, Gyuris A, Zhu H, Woolfenden S, Bronisz A, Nakano I, Chiocca EA, Bronson RT, Ligon KL, Sarkaria JN, Gygi SP, Michor F, Mitchison TJ, Charest A. A PDGFRa-driven mouse model of glioblastoma reveals a stathmin1-mediated mechanism of sensitivity to vinblastine. Nat Commun. 2018 08 06; 9(1):3116. PMID: 30082792
• Ricklefs FL, Alayo Q, Krenzlin H, Mahmoud AB, Speranza MC, Nakashima H, Hayes JL, Lee K, Balaj L, Passaro C, Rooj AK, Krasemann S, Carter BS, Chen CC, Steed T, Treiber J, Rodig S, Yang K, Nakano I, Lee H, Weissleder R, Breakefield XO, Godlewski J, Westphal M, Lamszus K, Freeman GJ, Bronisz A, Lawler SE, Chiocca EA. Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci Adv. 2018 03; 4(3):eaar2766. PMID: 29532035
• Rooj AK, Ricklefs F, Mineo M, Nakano I, Chiocca EA, Bronisz A, Godlewski J. MicroRNA-Mediated Dynamic Bidirectional Shift between the Subclasses of Glioblastoma Stem-like Cells. Cell Rep. 2017 06 06; 19(10):2026-2032. PMID: 28591575
• Godlewski J, Ferrer-Luna R, Rooj AK, Mineo M, Ricklefs F, Takeda YS, Nowicki MO, Salinska E, Nakano I, Lee H, Weissleder R, Beroukhim R, Chiocca EA, Bronisz A. MicroRNA Signatures and Molecular Subtypes of Glioblastoma: The Role of Extracellular Transfer. Stem Cell Reports. 2017 06 06; 8(6):1497-1505. PMID: 28528698
• Mineo M, Ricklefs F, Rooj AK, Lyons SM, Ivanov P, Ansari KI, Nakano I, Chiocca EA, Godlewski J, Bronisz A. The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches. Cell Rep. 2016 06 14; 15(11):2500-9. PMID: 27264189
• Ricklefs F, Mineo M, Rooj AK, Nakano I, Charest A, Weissleder R, Breakefield XO, Chiocca EA, Godlewski J, Bronisz A. Extracellular Vesicles from High-Grade Glioma Exchange Diverse Pro-oncogenic Signals That Maintain Intratumoral Heterogeneity. Cancer Res. 2016 05 15; 76(10):2876-81. PMID: 27013191
• Ansari KI, Ogawa D, Rooj AK, Lawler SE, Krichevsky AM, Johnson MD, Chiocca EA, Bronisz A, Godlewski J. Glucose-based regulation of miR-451/AMPK signaling depends on the OCT1 transcription factor. Cell Rep. 2015 May 12; 11(6):902-909. PMID: 25937278
• Godlewski J, Krichevsky AM, Johnson MD, Chiocca EA, Bronisz A. Belonging to a network--microRNAs, extracellular vesicles, and the glioblastoma microenvironment. Neuro Oncol. 2015 May; 17(5):652-62. PMID: 25301812
• Bronisz A, Wang Y, Nowicki MO, Peruzzi P, Ansari K, Ogawa D, Balaj L, De Rienzo G, Mineo M, Nakano I, Ostrowski MC, Hochberg F, Weissleder R, Lawler SE, Chiocca EA, Godlewski J. Extracellular vesicles modulate the glioblastoma microenvironment via a tumor suppression signaling network directed by miR-1. Cancer Res. 2014 Feb 01; 74(3):738-750. PMID: 24310399
• Peruzzi P, Bronisz A, Nowicki MO, Wang Y, Ogawa D, Price R, Nakano I, Kwon CH, Hayes J, Lawler SE, Ostrowski MC, Chiocca EA, Godlewski J. MicroRNA-128 coordinately targets Polycomb Repressor Complexes in glioma stem cells. Neuro Oncol. 2013 Sep; 15(9):1212-24. PMID: 23733246
• Bronisz A, Godlewski J, Wallace JA, Merchant AS, Nowicki MO, Mathsyaraja H, Srinivasan R, Trimboli AJ, Martin CK, Li F, Yu L, Fernandez SA, Pécot T, Rosol TJ, Cory S, Hallett M, Park M, Piper MG, Marsh CB, Yee LD, Jimenez RE, Nuovo G, Lawler SE, Chiocca EA, Leone G, Ostrowski MC. Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320. Nat Cell Biol. 2011 Dec 18; 14(2):159-67. PMID: 22179046
• Godlewski J, Nowicki MO, Bronisz A, Nuovo G, Palatini J, De Lay M, Van Brocklyn J, Ostrowski MC, Chiocca EA, Lawler SE. MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol Cell. 2010 Mar 12; 37(5):620-32. PMID: 20227367