Laboratory of Ischemic and Neurodegenerative Brain Research

Head
Prof. Ryszard Pluta, MD, PhD - phone. +48 / 22 60 86 540/469, This email address is being protected from spambots. You need JavaScript enabled to view it.

Technical staff
Sławomir Januszewski - phone. +48 22 60 86 469, This email address is being protected from spambots. You need JavaScript enabled to view it.

Research profile
• Complete brain ischemia: neuropathology, changes in genome and proteome
• Analysis of genes and proteins associated with Alzheimer's disease after brain ischemia
• Searching for common pathological mechanisms in ischemic brain and Alzheimer's disease
• Development of an ischemic model of Alzheimer's disease

Grants
• Method of producing a standardized rich polyphenolic nutraceutical, for use in the prevention of neurodegenerative diseases. Tango 2. The National Centre for Research and Development. prof. Anna Bogucka-Kocka (Main performer-Prof. R. Pluta) 04.2017-03.2020.
• Looking for the same pathological factors in brain ischemia and Alzheimer's disease: Genes. DEC-2013/09/B/NZ7/01345. National Science Centre. Prof. R. Pluta. 02.2014-02.2017.

Colaboration
domestic
• prof. Stanisław Jerzy Czuczwar, Medical University of Lublin, Lublin.
• prof. Anna Bogucka-Kocka, Medical University of Lublin, Lublin.
• prof. Janusz Kocki, Medical University of Lublin, Lublin.
• prof. Wanda Małgorzata Furmaga-Jabłońska, Medical University of Lublin Lublin.

foreign
• prof. Pavle Andjus, University of Belgrade, Belgrade, Serbia.

Research equipment
• Equipment for conducting experiments on rodents.
Research methods
• An experimental model of complete brain ischemia in the rat.

Selected publications

• Radenovic L, Nenadic M, Ułamek-Kozioł M, Januszewski S, Czuczwar SJ, Andjus PR, Pluta R. Heterogeneity in brain distribution of activated microglia and astrocytes in a rat ischemic model of Alzheimer’s disease after 2 years of survival. Aging (Albany NY). 2020;12:12251-12267.
• Pluta R, Ułamek-Kozioł M, Januszewski S, Czuczwar SJ. Participation of amyloid and tau protein in neuronal death and neurodegeneration after brain ischemia. Int J Mol Sci., 2020;21:4599.
• Pluta R, Ułamek-Kozioł M, Kocki J, Bogucki J, Januszewski S, Bogucka-Kocka A, Czuczwar SJ. Expression of the tau protein and amyloid protein precursor processing genes in the CA3 area of the hippocampus in the ischemic model of Alzheimer's disease in the rat. Mol Neurobiol., 2020;57:1281–1290.
• Pluta R, Ułamek-Kozioł M, Januszewski S, Czuczwar SJ. Shared genomic and proteomic contribution of amyloid and tau protein characteristic of Alzheimer's disease to brain ischemia. Int J Mol Sci., 2020;21:3186.
• Ułamek-Kozioł M, Czuczwar SJ, Januszewski S, Pluta R. Proteomic and genomic changes in tau protein, which are associated with Alzheimer's disease after ischemia-reperfusion brain injury. Int J Mol Sci., 2020;21:892.
• Pluta R (Ed.) Brain ischemia: Alzheimer’s disease mechanisms. Nova Science Publishers, Inc. New York. USA. 2019.
• Ułamek-Kozioł M, Czuczwar SJ, Kocki J, Januszewski S, Bogucki J, Bogucka-Kocka A, Pluta R. Dysregulation of autophagy, mitophagy, and apoptosis genes in the CA3 region of the hippocampus in the ischemic model of Alzheimer's disease in the rat. J Alzheimers Dis., 2019;72:1279-1286.
• Pluta R, Bogucka-Kocka A, Ułamek-Kozioł M, Bogucki J, Januszewski S, Kocki J, Czuczwar SJ. Ischemic tau protein gene induction as an additional key factor driving development of Alzheimer's phenotype changes in CA1 area of hippocampus in an ischemic model of Alzheimer's disease. Pharmacol Rep., 2018;70:881-884.
• Ułamek-Kozioł M, Kocki J, Bogucka-Kocka A, Januszewski S, Bogucki J, Czuczwar SJ, Pluta R. Autophagy, mitophagy and apoptotic gene changes in the hippocampal CA1 area in a rat ischemic model of Alzheimer's disease. Pharmacol Rep., 2017;69:1289-1294.
• Pluta R, Kocki J, Ułamek-Kozioł M, Petniak A, Gil-Kulik P, Januszewski S, Bogucki J, Jabłoński M, Brzozowska J, Furmaga-Jabłońska W, Bogucka-Kocka A, Czuczwar SJ. Discrepancy in expression of β-secretase and amyloid-β protein precursor in Alzheimer-related genes in the rat medial temporal lobe cortex following transient global brain ischemia. J Alzheimers Dis., 2016;51:1023-1031.
• Ułamek-Kozioł M, Kocki J, Bogucka-Kocka A, Petniak A, Gil-Kulik P, Januszewski S, Bogucki J, Jabłoński M, Furmaga-Jabłońska W, Brzozowska J, Czuczwar SJ, Pluta R. Dysregulation of autophagy, mitophagy and apoptotic genes in the medial temporal lobe cortex in an ischemic model of Alzheimer’s disease. J Alzheimers Dis., 2016;54:113-121.
• Pluta R, Kocki J, Ułamek-Kozioł M, Bogucka-Kocka A, Gil-Kulik P, Januszewski S, Jabłoński M, Petniak A, Brzozowska J, Bogucki J, Furmaga-Jabłońska W, Czuczwar SJ. Alzheimer-associated presenilin 2 gene is dysregulated in rat medial temporal lobe cortex after complete brain ischemia due to cardiac arrest. Pharmacol Rep., 2016;68:155-161.
• Kocki J, Ułamek-Kozioł M, Bogucka-Kocka A, Januszewski S, Jabłoński M, Gil-Kulik P, Brzozowska J, Petniak A, Furmaga-Jabłońska W, Bogucki J, Czuczwar SJ, Pluta R. Dysregulation of amyloid precursor protein, β-secretase, presenilin 1 and 2 genes in the rat selectively vulnerable CA1 subfield of hippocampus following transient global brain ischemia. J Alzheimers Dis., 2015;47:1047–1056.
• Pluta R, Jabłoński M, Ułamek-Kozioł M, Kocki J, Brzozowska J, Januszewski S, Furmaga-Jabłońska W, Bogucka-Kocka A, Maciejewski R, Czuczwar SJ. Sporadic Alzheimer's disease begins as episodes of brain ischemia and ischemically dysregulated Alzheimer's disease genes. Mol Neurobiol., 2013;48:500-515.
• Pluta R, Furmaga-Jabłońska W, Maciejewski R, Ułamek-Kozioł M, Jabłoński M. Brain ischemia activates β- and γ-secretase cleavage of amyloid precursor protein: Significance in sporadic Alzheimer’s Disease. Mol Neurobiol., 2013;47:425-434.
• Sekeljic V, Bataveljic D, Stamenkovic S, Ułamek M, Jabłoński M, Radenovic L, Pluta R, Andjus PR. Cellular markers of neuroinflammation and neurogenesis after ischemic brain injury in the long-term survival rat model. Brain Struct Funct., 2012;217:411-420.
• Kiryk A, Pluta R, Figiel I, Mikosz M, Ułamek M, Niewiadomska G, Jabłoński M, Kaczmarek L. Transient brain ischemia due to cardiac arrest causes irreversible long-lasting cognitive injury. Behav Brain Res., 2011;219:1-7.
  
•  Jabłoński M, Maciejewski R, Januszewski S, Ułamek M, Pluta R. One year follow up in ischemic brain injury and the role of Alzheimer factors. Physiol Res., 2011;60(Suppl. 1.): S113-S119.
• Pluta R, Januszewski S, Jabłoński M, Ułamek M. Factors in creepy delayed neuronal death in hippocampus following brain ischemia-reperfusion injury with long-term survival. Acta Neurochir., 2010;106(Suppl.):37-41.
• Pluta R, Ułamek M, Jabłoński M. Alzheimer’s mechanisms in ischemic brain degeneration. Anat Rec., 2009;292:1863-1881.
• Pluta R (Ed.) Ischemia-reperfusion pathways in Alzheimer’s disease. Nova Science Publishers, Inc. New York. USA. 2007.

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).

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