A5069362690- TGF-β signaling in diseases
- Cancer-related gene regulation
- Heat shock proteins research
- Cancer Cells and Metastasis
- Fibroblast Growth Factor Research
- Asthma and respiratory diseases
- Protein Tyrosine Phosphatases
- Galectins and Cancer Biology
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Stress Responses and Cortisol
- Peroxisome Proliferator-Activated Receptors
- Receptor Mechanisms and Signaling
- IL-33, ST2, and ILC Pathways
- Neonatal Respiratory Health Research
- Cancer Immunotherapy and Biomarkers
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Computational Drug Discovery Methods
- Protein Kinase Regulation and GTPase Signaling
- Monoclonal and Polyclonal Antibodies Research
- Toxin Mechanisms and Immunotoxins
- Endoplasmic Reticulum Stress and Disease
- Bacteriophages and microbial interactions
- NF-κB Signaling Pathways
University of Pittsburgh
2020-2025
University of Leeds
2017-2025
Institute of Structural and Molecular Biology
2020-2024
Medical University of Lodz
2011-2018
University of Warsaw
2015-2017
University of Alberta
2010
Protein-peptide interactions play essential functional roles in living organisms and their structural characterization is a hot subject of current experimental theoretical research. Computational modeling the structure protein-peptide usually divided into two stages: prediction binding site at protein receptor surface, then docking (and modeling) peptide known site. This paper presents comprehensive CABS-dock method for simultaneous search sites flexible docking, available as users friendly...
The recruitment of signaling proteins into activated receptor tyrosine kinases (RTKs) to produce rapid, high-fidelity downstream response is exposed the ambiguity random diffusion target site. Liquid-liquid phase separation (LLPS) overcomes this by providing elevated, localized concentrations required while impeding competitor ligands. Here, we show a subset phosphorylation-dependent RTK-mediated LLPS states. We then investigate formation phase-separated droplets comprising ternary complex...
While checkpoint blockade immunotherapies have widespread success, they rely on a responsive immune infiltrate; as such, treatments enhancing infiltration and preventing immunosuppression are of critical need. We previously generated αPD-1 resistant variants the murine HNSCC model MEER. entirely resistant, these tumors regress after single dose oncolytic vaccinia virus (VV). then VV-resistant MEER line to dissect immunologic features sensitive tumors. treatment both tumor types induced IFNγ,...
BiP is the only Hsp70 chaperone in endoplasmic reticulum (ER) and similar to other Hsp70s, its activity relies on nucleotide- substrate-controllable docking undocking of nucleotide-binding domain (NBD) substrate-binding (SBD). However, little known specific features conformational landscape that tune unique tasks ER environment. We present methyl NMR analysis cycle reveals surprising heterogeneity ATP-bound distinguishes from bacterial homologue DnaK. This unusual poise enables gradual...
The clinical presentation of asthma results from complex gene-gene and gene-environment interactions. natural variability the DNA sequence within NR3C1 gene affects activity glucocorticoid receptors (GCRs). is localized on chromosome 5q31-q32. coding for GCR comprises nine exons. structural domains determine biological functions functional domains. observed resistance to glucocorticosteroids normal metabolic profile Tth111I single nucleotide polymorphism (SNP) carriers due ER22/23EK that...
BACKGROUND: Although the development of novel diagnostic and treatment strategies concerning laryngeal cancer is highly intensive, survival rate remains virtually unchanged.Small non-coding RNAs appear to be very promising biomarkers -and so remain focus extensive investigation in cancer.OBJECTIVE: We examined expression five miRNA genes related whether they could potential biomarkers.METHODS: performed an analysis 47 patients diagnosed with cancer.The qPCR technique was used investigate...
Abstract The regulation of phosphatase activity is fundamental to the control intracellular signalling and in particular tyrosine kinase-mediated mitogen-activated protein kinase (MAPK) pathway. Shp2 a ubiquitously expressed its kinase-induced hyperactivity associated with many cancer types. In non-stimulated cells we find that binding adaptor Grb2, monomeric state, initiates independent phosphorylation. Grb2 forms bidentate interaction both N-terminal SH2 catalytic domains Shp2, releasing...
Vibrio cholerae, the marine bacterium responsible for diarrheal disease cholera, utilizes a multitude of virulence factors to cause disease. The importance two these factors, toxin co-regulated pilus (TCP) and cholera (CT), has been well documented pandemic O1 epidemic O139 serogroups. In contrast, endemic non-O1 non-O139 serogroups can localized outbreaks cholera-like illness, often in absence TCP CT. One mechanism used by strains is type VI secretion system (T6SS) export toxins across cell...
Receptor tyrosine kinase (RTK)-mediated hyperactivation of the MAPK/Erk pathway is responsible for a large number pathogenic outcomes including many cancers. Considerable effort has been directed at targeting this with varying degrees long term therapeutic success. Under non-stimulated conditions Erk bound to adaptor protein Shc preventing aberrant signalling by sequestering from activation Mek. Activated RTK recruits Shc, via its phosphotyrosine binding (PTB) domain (ShcPTB), precipitating...
Abstract TGFβ is a key regulator of oral squamous cell carcinoma (OSCC) progression, and its potential role as therapeutic target has been investigated with limited success. This study evaluates two novel inhibitors mono or combinatorial therapy anti–PD-L1 antibodies (α-PD-L1 Ab) in murine OSCC model. Immunocompetent C57BL/6 mice bearing malignant lesions induced by 4-nitroquinoline 1-oxide (4-NQO) were treated for 4 weeks mRER (i.p., 50 μg/d) mmTGFβ2-7m (10 μg/d delivered osmotic pumps)...
<b><i>Background/Aims:</i></b> The <i>PIK3CD</i> gene encodes the delta catalytic subunit of phosphoinositide 3-kinase (PI3K), an element neuregulin 1-downstream ErbB4-PI3K signaling pathway, which was recently identified as a molecular target for treatment schizophrenia. aim study to examine effect haloperidol (HALO), clozapine (CLO), olanzapine (OLA), quetiapine (QUE) and amisulpride (AMI) on mRNA protein expression genes encoding elements in human...
Transforming growth factor-β1 (TGF-β1) is an important fibrogenic and immunomodulatory cytokine participating in the pathogenesis of a number illnesses related to growth, differentiation migration cells. It also plays key role inflammation, atherosclerosis, vascular inflammation asthma. The aim present study was evaluate association between expression TGF-β1 gene its genetic polymorphisms, disease phenotype. comprised 173 patients with asthma, as well 163 healthy volunteers control group....
The aim of the present study was to identify polymorphic forms nuclear receptor subfamily 3, group C, member 1 (NR3C1) and transforming growth factor β1 (TGF-β1) genes evaluate their impact on expression levels interleukin (IL)-5 IL‑15 in asthma. conducted a control consisting 91 people (54 women 37 men). patient consisted 130 participants (86 44 Genotyping performed by polymerase chain reaction‑restriction fragment length polymorphism (PCR‑RFLP) PCR‑high resolution melting (HRM) methods....
Abstract The complex multistep activation cascade of Ire1 involves changes in the conformation and oligomeric state. enhances ER folding capacity, part by overexpressing Hsp70 molecular chaperone BiP; turn, BiP provides tight negative control activation. This study demonstrates that regulates through a direct interaction with oligomers. Particularly, we demonstrated binding luminal domain (LD) to unfolded protein substrates not only trigger conformational Ire1-LD favour formation oligomers...
The complex multistep activation cascade of Ire1 involves changes in the conformation and oligomeric state. enhances ER folding capacity, part by overexpressing Hsp70 molecular chaperone BiP; turn, BiP provides tight negative control activation. This study demonstrates that regulates through a direct interaction with oligomers. Particularly, we demonstrated binding luminal domain (LD) to unfolded protein substrates not only trigger conformational Ire1-LD favour formation oligomers but also...
Abstract Receptor tyrosine kinases (RTKs) are typically activated through a precise sequence of intracellular phosphorylation events starting with residue on the activation loop (A-loop) kinase domain (KD). From this point mono-phosphorylated enzyme is active, but subject to stringent regulatory mechanisms which can vary dramatically across different RTKs. In absence extracellular stimulation, fibroblast growth factor receptor 2 (FGFR2) exists in state catalytic activity regulated allow...
13 C Methyl-labeled amino acids are prepared by a Pd-catalyzed C(sp 3 )–H functionalization and can be incorporated into human receptor extracellular domains with multiple disulfides using mammalian suspension-cultured HEK293 cells.