Michal Lazniewski

For the last two years, the COVID-19 pandemic has continued to bring consternation on most of the world. According to recent WHO estimates, there have been more than 5.6 million deaths worldwide. The virus continues to evolve all over the world, thus requiring both vigilance and the necessity to find and develop a variety of therapeutic treatments,...

CD71 + erythroid cells (CECs) have been recently recognized in both neonates and cancer patients as potent immunoregulatory cells. Here, we show that in mice early-stage CECs expand in anemia, have high levels of arginase 2 (ARG2) and reactive oxygen species (ROS). In the spleens of anemic mice, CECs expansion-induced L-arginine depletion suppresse...

Oxidative stress, caused by the imbalance between reactive species generation and the dysfunctional capacity of antioxidant defenses, is one of the characteristic features of cancer. Here, we quantified hydrogen peroxide in the tumor microenvironment and demonstrated that hydrogen peroxide concentrations are elevated in tumor interstitial fluid iso...

Introduction The Hemagglutinin (HA) protein is responsible for binding the virus to host cells with sialic acid (glycans) on the membranes, thus, potential inhibitors that bind strongly to the active site of HA would have the ability to block the viral life-cycle. This elucidated the importance of HA's three dimensional structure in computer-aided...

Several TBC1D24 variants are causally involved in the development of profound, prelingual hearing loss (HL) and different epilepsy syndromes inherited in an autosomal recessive manner. Only two TBC1D24 pathogenic variants have been linked with postlingual progressive autosomal dominant HL (ADHL). To determine the role of TBC1D24 in the development...

Erythroid progenitor cells (EPCs) have been recently recognized as potent immunoregulatory cells with defined roles in fetomaternal tolerance and immune response to infectious agents in neonates and cancer patients. Here, we show that early-stage EPCs are enriched in anemia, have high levels of arginase 2 (ARG2) and reactive oxygen species (ROS). E...

In recent years, high-throughput techniques have revealed considerable structural organization of the human genome with diverse regions of the chromatin interacting with each other in the form of loops. Some of these loops are quite complex and may encompass regions comprised of many interacting chain segments around a central locus. Popular techni...

Metastasis to distant organs is a major cause for solid cancer mortality, and the acquisition of migratory and invasive phenotype is a key factor in initiation of malignancy. In this study we investigated the contribution of Mixed-Lineage Kinase 4 (MLK4) to aggressive phenotype of breast cancer cells. Our TCGA cancer genomic data analysis revealed...

Mixed Lineage Kinase 4 (MLK4) is a serine/threonine kinase that plays a role in a variety of cellular processes, including migration, apoptosis and proliferation. It belongs to the family of MAP3 kinases, which regulate the activity of specific MAPKs (mitogen-activated protein kinases). MLK4 is the least described member of the family and it was pr...

The eukaryotic genome, constituting several billion base pairs, must be contracted to fit within the volume of a nucleus where the diameter is on the scale of μm. The 3D structure and packing of such a long sequence cannot be left to pure chance, as DNA must be efficiently used for its primary roles as a matrix for transcription and replication. In...

Acute myeloid leukemia is a malignant disease of immature myeloid cells. Despite significant therapeutic effects of differentiation-inducing agents in some acute myeloid leukemia subtypes, the disease remains incurable in a large fraction of patients. Here, we show that SK053, a thioredoxin inhibitor, induces differentiation and cell death of acute...

Most of the 19 mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) involved in mitochondrial protein synthesis are already linked to specific entities, one of the exceptions being PARS2 mutations for which pathogenic significance is not finally validated. The aim of the study was to characterize the PARS2- related phenotype. Three siblings with bia...

DNA is the longest polymer present in a living cell. In humans, the 3 billion base pair double-stranded DNA (dsDNA) duplex would stretch out to 1 m for the haploid (gamete) and 2 m for a diploid (somatic cell), yet the dsDNA fits inside a nucleus with a diameter ranging from 6 to 8 µm for lymphocyte to HeLa cells. Here we review our current underst...

Hemagglutinin (HA) is a transmembrane protein of the influenza A virus and a key component in its life cycle. The protein allows the virus to enter a host cell by recognizing specific glycans attached to transmembrane proteins of the host, which leads to viral endocytosis. In recent years, significant progress has been made in understanding the str...

In one more years, we will 'celebrate' an exact centenary of the Spanish flu pandemic. With the rapid evolution of the influenza virus, the possibility of novel pandemic remains ever a concern. This review covers our current knowledge of the influenza A virus: on the role of RNA in translation, replication, what is known of the expressed proteins a...

Background & aims: Macro-aspartate aminotransferase (macro-AST) manifests as persistent elevation of AST levels, due to association of the protein with immunoglobulins in the circulation macro-AST is a rare, benign condition without a previously confirmed genetic basis. Methods: Whole exome sequencing (WES)-based screening was performed on 32 pa...

Background Hearing loss and ovarian dysfunction are key features of Perrault syndrome (PRLTS) but the clinical and pathophysiological features of hearing impairment in PRLTS individuals have not been addressed. Mutations in one of five different genes HSD17B4, HARS2, LARS2, CLPP or TWNK (previous symbol C10orf2) cause the autosomal recessive disord...

The influenza virus type A (IVA) is an important pathogen which is able to cause annual epidemics and even pandemics. This fact is the consequence of the antigenic shifts and drifts capabilities of IVA, caused by the high mutation rate and the reassortment capabilities of the virus. The hemagglutinin (HA) protein constitutes the main IVA antigen an...

Significance Cellular function is tightly regulated by large molecular assemblies such as the proteasome, which is involved in the removal of damaged or misfolded proteins. Proteasome substrates are unfolded by complexes such as valosin-containing protein-like ATPase of Thermoplasma acidophilum (VAT) via a process that is coupled to ATP hydrolysis....

Although differentiation-inducing agents have significantly improved the management of acute promyelocytic leukemia, no significant progress has been made in the treatment of other acute myeloid leukemias (AML). Numerous proteins involved in tumor development have so-called allosteric disulfide bonds amenable to modifications affecting protein stru...

The Cyclin-Dependent Kinases (CDKs) are the core components coordinating eukaryotic cell division cycle. Generally the crystal structure of CDKs provides information on possible molecular mechanisms of ligand binding. However, reliable and robust estimation of ligand binding activity has been a challenging task in drug design. In this regard, vario...

Targeting epigenetic modifiers, such as histone deacetylases, bromodomain and extraterminal (BET) domains or methyltransferases as well as the use of differentiation-inducing agents (all-trans retinoic acid and arsenic trioxide) are rising hopes for development of effective therapeutic strategies for acute myeloid leukemia (AML). However, despite s...

C16orf57 encodes a human protein of unknown function, and mutations in the gene occur in poikiloderma with neutropenia (PN), which is a rare, autosomal recessive disease. Interestingly, mutations in C16orf57 were also observed among patients diagnosed with Rothmund-Thomson syndrome (RTS) and dyskeratosis congenita (DC), which are caused by mutation...

Molecular recognition plays a fundamental role in all biological processes, and that is why great efforts have been made to understand and predict protein-ligand interactions. Finding a molecule that can potentially bind to a target protein is particularly essential in drug discovery and still remains an expensive and time-consuming task. In silico...

Docking is one of the most commonly used techniques in drug design. It is used for both identifying correct poses of a ligand in the binding site of a protein as well as for the estimation of the strength of protein-ligand interaction. Because millions of compounds must be screened, before a suitable target for biological testing can be identified,...

Squalene epoxidase (SE) is a key flavin adenine dinucleotide (FAD)-dependent enzyme of ergosterol and cholesterol biosynthetic pathways and an attractive potential target for drugs used to inhibit the growth of pathogenic fungi or to lower cholesterol level. Although many studies on allylamine drugs activity have been published during the last 30 y...

Processing of exogenous glycerol esters is an initial step in energy derivation for many bacterial cells. Lipid-rich environments settled by a variety of organisms exert strong evolutionary pressure for establishing enzymatic pathways involved in lipid metabolism. However, a certain number of enzymes involved in this process remain unknown since th...