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Author Pawel Stocki

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Single domain shark VNAR antibodies neutralize SARS-CoV-2 infection in vitro.

Aziz Gauhar, Cyril V Privezentzev, Mykhaylo Demydchuk, Tanja Gerlza, Julia Rieger, Andreas J Kungl, Frank S Walsh, J Lynn Rutkowski, Pawel Stocki,

Single domain shark variable domain of new antigen receptor (VNAR) antibodies can offer a viable alternative to conventional Ig-based monoclonal antibodies in treating COVID-19 disease during the current pandemic. Here we report the identification of neutralizing single domain VNAR antibodies selected against the severe acute respiratory syndrome coronavirus 2 spike ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(11):e21970]

Cited: 0 times

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Blood-brain barrier transport using a high affinity, brain-selective VNAR antibody targeting transferrin receptor 1.

Pawel Stocki, Jaroslaw Szary, Charlotte L M Rasmussen, Mykhaylo Demydchuk, Leandra Northall, Diana Bahu Logan, Aziz Gauhar, Laura Thei, Torben Moos, Frank S Walsh, J Lynn Rutkowski,

Transfer across the blood-brain barrier (BBB) remains a significant hurdle for the development of biopharmaceuticals with therapeutic effects within the central nervous system. We established a functional selection method to identify high affinity single domain antibodies to the transferrin receptor 1 (TfR1) with efficient biotherapeutic delivery across the BBB. A ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2021, 35(2):e21172]

Cited: 6 times

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Brain delivery of biologics using a cross-species reactive transferrin receptor 1 VNAR shuttle.

Dag Sehlin, Pawel Stocki, Tobias Gustavsson, Greta Hultqvist, Frank S Walsh, J Lynn Rutkowski, Stina Syvänen,

Transferrin receptor 1 (TfR1) mediated transcytosis is an attractive strategy to enhance brain uptake of protein drugs, but translation remains a challenge. Here, a single domain shark antibody VNAR fragment (TXB2) with similar affinity to murine and human TfR1 was used to shuttle protein cargo into the brain. TXB2 was ... Read more >>

FASEB J (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2020, 34(10):13272-13283]

Cited: 4 times

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A single domain shark antibody targeting the transferrin receptor 1 delivers a TrkB agonist antibody across the blood brain barrier to provide full neuroprotection in a mouse model of Parkinson’s Disease

Emily Clarke, Liz Sinclair, Edward Fletcher, Alicja Krawczun-Rygmaczewska, Susan Duty, Pawel Stocki, Lynn Rutowski, Patrick Doherty, Frank Walsh,

Single domain shark antibodies that bind to the transferrin receptor 1 (TfR1) on brain endothelial cells can be used to shuttle antibodies and other cargos across the blood brain barrier (BBB). We have fused one of these (TXB4) to differing regions of TrkB and TrkC neurotrophin receptor agonist antibodies (AAb) ... Read more >>

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Blood-brain barrier transport using a high-affinity, brain-selective VNAR (Variable Domain of New Antigen Receptor) antibody targeting transferrin receptor 1

Pawel Stocki, Jaroslaw Szary, Charlotte LM Rasmussen, Mykhaylo Demydchuk, Leandra Northall, Diana Bahu Logan, Aziz Gauhar, Laura Thei, Torben Moos, Frank Walsh, Lynn Rutkowski,

<h4>ABSTRACT</h4> Transfer across the blood-brain barrier (BBB) remains a significant hurdle for the development of biopharmaceuticals with therapeutic effects within the central nervous system. We established a functional selection method to identify high-affinity single domain antibodies to the transferrin receptor 1 (TfR1) with efficient biotherapeutic delivery across the BBB. <h4>Methods</h4> ... Read more >>

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Structural and functional characterization of a DARPin which inhibits Ras nucleotide exchange.

Sandrine Guillard, Paulina Kolasinska-Zwierz, Judit Debreczeni, Jason Breed, Jing Zhang, Nicolas Bery, Rose Marwood, Jon Tart, Ross Overman, Pawel Stocki, Bina Mistry, Christopher Phillips, Terence Rabbitts, Ronald Jackson, Ralph Minter,

Ras mutations are the oncogenic drivers of many human cancers and yet there are still no approved Ras-targeted cancer therapies. Inhibition of Ras nucleotide exchange is a promising new approach but better understanding of this mechanism of action is needed. Here we describe an antibody mimetic, DARPin K27, which inhibits ... Read more >>

Nat Commun (Nature communications)
[2017, 8:16111]

Cited: 33 times

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Altered apolipoprotein C expression in association with cognition impairments and hippocampus volume in schizophrenia and bipolar disorder.

Christian Knöchel, Jonathan Kniep, Jason D Cooper, Michael Stäblein, Sofia Wenzler, Jan Sarlon, David Prvulovic, David E J Linden, Sabine Bahn, Pawel Stocki, Sureyya Ozcan, Gilberto Alves, Andre F Carvalho, Andreas Reif, Viola Oertel-Knöchel,

Proteomic analyses facilitate the interpretation of molecular biomarker probes which are very helpful in diagnosing schizophrenia (SZ). In the current study, we attempt to test whether potential differences in plasma protein expressions in SZ and bipolar disorder (BD) are associated with cognitive deficits and their underlying brain structures. Forty-two plasma ... Read more >>

Eur Arch Psychiatry Clin Neurosci (European archives of psychiatry and clinical neuroscience)
[2017, 267(3):199-212]

Cited: 2 times

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Molecular serum signature of treatment resistant depression.

Tillmann Ruland, Man K Chan, Pawel Stocki, Laura Grosse, Matthias Rothermundt, Jason D Cooper, Volker Arolt, Sabine Bahn,

<h4>Rationale</h4>A substantial number of patients suffering from major depressive disorder (MDD) do not respond to multiple trials of anti-depressants, develop a chronic course of disease and become treatment resistant. Most of the studies investigating molecular changes in treatment-resistant depression (TRD) have only examined a limited number of molecules and genes. ... Read more >>

Psychopharmacology (Berl) (Psychopharmacology)
[2016, 233(15-16):3051-3059]

Cited: 5 times

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Inhibition of the FKBP family of peptidyl prolyl isomerases induces abortive translocation and degradation of the cellular prion protein.

Pawel Stocki, Maxime Sawicki, Charles E Mays, Seo Jung Hong, Daniel C Chapman, David Westaway, David B Williams,

Prion diseases are fatal neurodegenerative disorders for which there is no effective treatment. Because the cellular prion protein (PrP(C)) is required for propagation of the infectious scrapie form of the protein, one therapeutic strategy is to reduce PrP(C) expression. Recently FK506, an inhibitor of the FKBP family of peptidyl prolyl ... Read more >>

Mol Biol Cell (Molecular biology of the cell)
[2016, 27(5):757-767]

Cited: 6 times

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Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules.

Daniel C Chapman, Pawel Stocki, David B Williams,

Human cytomegalovirus uses a variety of mechanisms to evade immune recognition through major histocompatibility complex class I molecules. One mechanism mediated by the immunoevasin protein US2 causes rapid disposal of newly synthesized class I molecules by the endoplasmic reticulum-associated degradation pathway. Although several components of this degradation pathway have been ... Read more >>

PLoS One (PloS one)
[2015, 10(12):e0145458]

Cited: 4 times

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Depletion of cyclophilins B and C leads to dysregulation of endoplasmic reticulum redox homeostasis.

Pawel Stocki, Daniel C Chapman, Lori A Beach, David B Williams,

Protein folding within the endoplasmic reticulum is assisted by molecular chaperones and folding catalysts that include members of the protein-disulfide isomerase and peptidyl-prolyl isomerase families. In this report, we examined the contributions of the cyclophilin subset of peptidyl-prolyl isomerases to protein folding and identified cyclophilin C as an endoplasmic reticulum ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2014, 289(33):23086-23096]

Cited: 19 times

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The immunosuppressive activity of heat shock protein 70.

Pawel Stocki, Anne M Dickinson,

Heat shock protein 70 (HSP70) has previously been described as a potent antitumour vaccine. The mechanism relied on the ability of tumour derived HSP70 to associate with antigenic peptides, which, when cross presented, elicited a T cell mediated antitumour response. Subsequently, HSP70 was incorrectly described as a potent adjuvant of ... Read more >>

Autoimmune Dis (Autoimmune diseases)
[2012, 2012:617213]

Cited: 22 times

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Inducible heat shock protein 70 reduces T cell responses and stimulatory capacity of monocyte-derived dendritic cells.

Pawel Stocki, Xiao N Wang, Anne M Dickinson,

Heat shock protein 70 (Hsp70) has gained a lot of attention in the past decade due to its potential immunoregulatory functions. Some of the described proinflammatory functions of Hsp70 became controversial as they were based on recombinant Hsp70 proteins specimens, which were later shown to be endotoxin-contaminated. In this study ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2012, 287(15):12387-12394]

Cited: 34 times

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HSP70 natively and specifically associates with an N-terminal dermcidin-derived peptide that contains an HLA-A*03 antigenic epitope.

Pawel Stocki, Xiao N Wang, Nicholas J Morris, Anne M Dickinson,

Tumor cells very often have elevated expression of HSP70, the anti-apoptotic properties of which contribute to overall tumor survival. Independent of its anti-apoptotic properties, HSP70 was also suggested to be involved in the antigen presentation process by chaperoning cytosolic peptides, thus protecting them from rapid degradation and securing the peptide ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2011, 286(14):12803-12811]

Cited: 13 times

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Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA).

Pawel Stocki, Nicholas J Morris, Christian Preisinger, Xiao N Wang, Walter Kolch, Gabriele Multhoff, Anne M Dickinson,

Heat shock protein 70 (HSPA) is a molecular chaperone which has been suggested to shuttle human leukocyte antigen (HLA) epitope precursors from the proteasome to the transporter associated with antigen processing. Despite the reported observations that peptides chaperoned by HSPA are an effective source of antigens for cross-priming, little is ... Read more >>

Cell Stress Chaperones (Cell stress & chaperones)
[2010, 15(5):729-741]

Cited: 11 times

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Correlation of Hsp70-1 and Hsp70-2 gene expression with the degree of graft-versus-host reaction in a rat skin explant model.

Peter Novota, Lisbet Sviland, Severin Zinöcker, Pawel Stocki, Yesilda Balavarca, Heike Bickeböller, Bent Rolstad, Xiao N Wang, Anne M Dickinson, Ralf Dressel,

<h4>Background</h4>Graft-versus-host disease (GVHD) is the most serious complication after allogeneic hematopoietic stem-cell transplantation. A human skin explant assay has been used to predict the risk of GVHD in patients by histological grading of graft-versus-host reactions (GVHR). New molecular markers of GVHR might help to further increase the predictive value of ... Read more >>

Transplantation (Transplantation)
[2008, 85(12):1809-1816]

Cited: 10 times

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Hsp70 chaperone machine remodels protein aggregates at the initial step of Hsp70-Hsp100-dependent disaggregation.

Szymon Zietkiewicz, Agnieszka Lewandowska, Pawel Stocki, Krzysztof Liberek,

Exposure to temperatures over a certain limit leads to massive protein aggregation in the cell. Disaggregation of such aggregates is largely dependent on the Hsp100 and Hsp70 chaperones. The exact role of the Hsp70 chaperone machine (composed of DnaK, DnaJ, and GrpE) in the Hsp100-dependent process remains unknown. In this ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2006, 281(11):7022-7029]

Cited: 58 times

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