Ivan Ivanov

Ivan Ivanov
Bulgarian Academy of Sciences | BAS · Department of Gene Regulations

Doctor of Philosophy

About

243
Publications
21,699
Reads
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3,858
Citations
Citations since 2016
37 Research Items
1489 Citations
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
Additional affiliations
January 1996 - February 2016
University of Chemical Technology and Metallurgy, Sofia, Bulgaria
Position
  • Professor
Description
  • Lecture courses: Biochemistry (BS and MS students) Biochemistry of the Secondary Metabolism (MS students) Genetic Engineering (MS students)
January 1980 - October 2015
Bulgarian Academy of Sciences
Position
  • Professor

Publications

Publications (243)
Article
Full-text available
High-fiber plant foods contain lignans that are converted to bioactive enterolignans, enterolactone (ENL) and enterodiol (END) by gut bacteria. Previously, we conducted an intervention study to gain mechanistic insight into the potential chemoprotective effects of flaxseed lignan supplementation (secoisolariciresinol diglucoside; SDG) compared to a...
Article
Full-text available
Ovarian granulosa cell tumors (GCTs) are rare sex cord-stromal tumors, accounting for ~5% ovarian tumors. The etiology of GCTs remains poorly defined. Genetically engineered mouse models are potentially valuable for understanding the pathogenesis of GCTs. Mice harboring constitutively active TGFβ signaling (TGFBR1-CA) develop ovarian GCTs that phen...
Article
Despite recent progress recognizing the importance of aryl hydrocarbon receptor (Ahr)-dependent signaling in suppressing colon tumorigenesis, its role in regulating colonic crypt homeostasis remains unclear. To assess the effects of Ahr on intestinal epithelial cell heterogeneity and functional phenotypes, we utilized single-cell transcriptomics an...
Article
Full-text available
Our objective is to reveal the molecular mechanism of the anti-inflammatory action of low-molecular-weight heparin (LMWH) based on its influence on the activity of two key cytokines, IFNγ and IL-6. The mechanism of heparin binding to IFNγ and IL-6 and the resulting inhibition of their activity were studied by means of extensive molecular-dynamics s...
Article
Full-text available
Streptococcus equi subsp. equi (SEE) is a host-restricted bacterium that causes the common infectious upper respiratory disease known as strangles in horses. Perpetuation of SEE infection appears attributable to inapparent carrier horses because it neither persists long-term in the environment nor infects other host mammals or vectors, and infectio...
Article
Assessing intestinal development and host-microbe interactions in healthy human infants requires non-invasive approaches. We have shown that the transcriptome of exfoliated epithelial cells in feces can differentiate breast and formula-fed infants and term and preterm infants. However, it is not fully understood which regions of the intestine that...
Article
The mutational genetic landscape of colorectal cancer has been extensively characterized; however, the ability of “cooperation response genes” to modulate the function of cancer “driver” genes remains largely unknown. In this study, we investigate the role of aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, in modulating on...
Article
The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that senses xenobiotics, diet, and gut microbial-derived metabolites, is increasingly recognized as a key regulator of intestinal biology. However, its effects on the function of colonic stem and progenitor cells remain largely unexplored. Here, we observed that inducible...
Preprint
Full-text available
Timely control of the cytokine release syndrome (CRS) at the severe stage of COVID-19 is key to improving the treatment success and reducing the mortality rate. The inhibition of the activity of the two key cytokines, IFNγ and IL-6, can significantly reduce or even reverse the development of the cytokine storm. The objective of our investigations i...
Article
Full-text available
Background: Inclusion bodies (IBs) are protein aggregates in recombinant bacterial cells containing mainly the target recombinant protein. Although it has been shown that IBs contain functional proteins along with protein aggregates, their direct application as pharmaceuticals is hindered by their heterogeneity and hazardous contaminants with bact...
Preprint
Full-text available
Background Inclusion bodies (IBs) are protein aggregates in recombinant bacterial cells containing mainly the target recombinant protein. Although it has been shown that IBs contain functional proteins along with protein aggregates, their direct application as pharmaceuticals is hindered by their heterogeneity and hazardous contaminants with bacter...
Preprint
Full-text available
Background Inclusion bodies (IBs) are protein aggregates in recombinant bacterial cells containing mainly the target recombinant protein. Although it has been shown that IBs contain functional proteins along with protein aggregates, their direct application as pharmaceuticals is hindered by their heterogeneity and hazardous contaminants with bacter...
Article
Full-text available
Evaluating the health and function of the gastrointestinal tract can be challenging in all species, but is especially difficult in horses due to their size and length of the gastrointestinal (GI) tract. Isolation of mRNA of cells exfoliated from the GI mucosa into feces (i.e., the exfoliome) offers a novel means of non-invasively examining the gene...
Article
Consumption of a high-fat diet has been associated with an increased risk of developing colorectal cancer (CRC). However, the effects of the interaction between dietary fat content and the aryl hydrocarbon receptor (AhR) on colorectal carcinogenesis remain unclear. Mainly known for its role in xenobiotic metabolism, AhR has been identified as an im...
Article
Background: Microbial metabolism of lignans from high-fiber plant foods produces bioactive enterolignans, such as enterolactone (ENL) and enterodiol (END). Enterolignan exposure influences cellular pathways important to cancer risk and is associated with reduced colon tumorigenesis in animal models and lower colorectal cancer risk in humans. Obje...
Article
Full-text available
Type 2 diabetes mellitus (T2DM) induced hemorheological disturbances leading to pathological changes in the whole blood viscosity (WBV), in blood coagulation and to the clots` formation. The study aims to investigate kinetics of the induced in vitro blood clots in T2DM patients and in healthy donors and morphological characteristics of the experime...
Article
Multicomponent therapy has gained interest for its potential to synergize and subsequently lower the effective dose of each constituent required to reduce colon cancer risk. We have previously showed that rapidly cycling Lgr5 stem cells are exquisitely sensitive to extrinsic dietary factors that modulate colon cancer risk. In the present study, we...
Article
Motivation: Canalizing genes enforce broad corrective actions on cellular processes for the purpose of biological robustness maintaining a constant phenotype to remain unchanged in spite of genetic mutations or environmental perturbations. Despite their central role in biological systems, the observation/detection of canalizing genes is often impe...
Preprint
Full-text available
We propose a Bayesian method for the classification of 16S rRNA metagenomic profiles of bacterial abundance, by introducing a Poisson-Dirichlet-Multinomial hierarchical model for the sequencing data, constructing a prior distribution from sample data, calculating the posterior distribution in closed form; and deriving an Optimal Bayesian Classifier...
Article
Full-text available
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used classes of medications in the world, yet they induce an enteropathy that is associated with high morbidity and mortality. A major limitation to better understanding the pathophysiology and diagnosis of this enteropathy is the difficulty of obtaining information about...
Article
Full-text available
Ranking feature sets for phenotype classification based on gene expression is a challenging issue in cancer bioinformatics. When the number of samples is small, all feature selection algorithms are known to be unreliable, producing significant error, and error estimators suffer from different degrees of imprecision. The problem is compounded by the...
Article
Full-text available
In order to obtain glycosylated human interferon-gamma (hIFNγ) and its highly prone to aggregation mutant K88Q, a secretory expression in insect cells was employed. To facilitate recombinant proteins purification, detection and stability the baculovirus expression vectors were constructed to bear N-terminal His6-FLAG tag. Although the obtained prot...
Article
Full-text available
Human interferon gamma (hIFNγ) plays a key role in the immune system and therefore this cytokine has many current and future therapeutic applications. hIFNγ is well known with its aggregation propensity and despite its clinical use, there is not much data about the stabilization of hIFNγ preparations. Nowadays, substantial evidence indicates that t...
Chapter
This chapter reviews the factors that contribute to the development of the gut microbiota in the neonate, including host genetics, the impact of colonization on host health and gene expression, and host-microbe interactions. It focuses on how gut microbiota are modulated by host genetics and external factors to the host. The chapter also reviews ho...
Article
Full-text available
During colon cancer, epigenetic alterations contribute to the dysregulation of major cellular functions and signaling pathways. Modifications in chromatin signatures such as H3K4me3 and H3K9ac, which are associated with transcriptionally active genes, can lead to genomic instability and perturb the expression of gene sets associated with oncogenic...
Article
Dietary fermentable fiber generates short‐chain fatty acids (SCFA), e.g., butyrate, in the colonic lumen which serves as a chemoprotective histone deacetylase inhibitor and/or as an acetylation substrate for histone acetylases. In addition, n‐3 polyunsaturated fatty acids (n‐3 PUFA) in fish oil can affect the chromatin landscape by acting as ligand...
Chapter
Recent studies have challenged the paradigm that bacteria do not age and are immortal. Stewart et al. (PLoS Biology, 2005, 3(2), e45) provided an intriguing evidence that during division Escherichia coli K-12 exhibits functional asymmetry, leaving behind a mother cell with delayed growth and survival rate and a younger daughter cell, empowered to s...
Conference Paper
Ranking feature sets for phenotype classification based on gene expression is one of the most challenging issues in bioinformatics. When the number of samples is small, all feature-selection algorithms are known to be unreliable and error estimators suffer to different degrees of imprecision. The problem is compounded by the fact that the accuracy...
Article
The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites. Unfortunately, baseline data describing genome-wide coding and long-noncoding gene expression profiles in the healthy...
Article
Full-text available
Most cancer research now involves one or more assays profiling various biological molecules, e.g., messenger RNA and micro RNA, in samples collected on the same individuals. The main interest with these genomic data sets lies in the identification of a subset of features that are active in explaining the dependence between platforms. To quantify th...
Article
Full-text available
With the identification of Lgr5 as a definitive marker for intestinal stem cells, we used the highly novel, recently described, Lgr5-EGFP-IRES-cre ERT2 knock in mouse model. Mice were injected with azoxymethane (AOM, a colon carcinogen) or saline (control) and fed a chemo-protective diet containing n-3 fatty acids and fermentable fiber (n-3 PUFA+pe...
Research
Full-text available
With the identification of Lgr5 as a definitive marker for intestinal stem cells, we used the highly novel, recently described, Lgr5-EGFP-IRES-cre ER T2 knock in mouse model. Mice were injected with azoxymethane (AOM, a colon carcinogen) or saline (control) and fed a chemo-protective diet containing n-3 fatty acids and fermentable fiber (n-3 PUFAþp...
Article
There is mounting evidence that noncoding microRNAs (miRNA) are modulated by select chemoprotective dietary agents. For example, recently we demonstrated that the unique combination of dietary fish oil (containing n-3 fatty acids) plus pectin (fermented to butyrate in the colon) (FPA) up-regulates a subset of putative tumor suppressor miRNAs in int...
Article
An application of the optimal Bayesian classification (OBC) and Bayesian error estimate (BEE) was demonstrated in identifying multivariate gene interactions in RNA-Seq data for the purpose of differentiating biological phenotypes. Using 858 genes selected by prior knowledge in a preclinical RNA-Seq dataset, we identified genes that in combination y...
Article
This study tested the hypothesis that the fecal bacterial genera of breast-fed (BF) and formula-fed (FF) infants differ and that human milk oligosaccharides (HMO) modulate the microbiota of BF infants. Fecal samples were obtained from BF (n = 16) or FF (n = 6) infants at 3-month postpartum. Human milk were collected on the same day when feces were...
Article
Full-text available
Background Sequencing datasets consist of a finite number of reads which map to specific regions of a reference genome. Most effort in modeling these datasets focuses on the detection of univariate differentially expressed genes. However, for classification, we must consider multiple genes and their interactions.ResultsThus, we introduce a hierarch...
Article
The early postnatal period is a critical window for intestinal and immune maturation. Intestinal development and microbiome diversity and composition differ between breast- (BF) and formula-fed (FF) infants. Mechanistic examination into host–microbe relationships in healthy infants has been hindered by ethical constraints surrounding tissue biopsie...
Conference Paper
Full-text available
The E. coli expression system is a preferable choice for production of therapeutic proteins due to the low cost and simplicity of cultivation. The high expression level and lack of glycosylation, however, often lead to increased aggregation of the target protein in the form of “inclusion bodies” (IBs) where the protein is biologically inactive. Pro...
Article
Full-text available
The state and development of the intestinal epithelium is vital for infant health, and increased understanding in this area has been limited by an inability to directly assess epithelial cell biology in the healthy newborn intestine. To that end, we have developed a novel, noninvasive, molecular approach that utilizes next generation RNA sequencing...
Article
Full-text available
Pneumonia caused by Rhodococcus equi is a common cause of disease and death in foals. Although agent and environmental factors contribute to the incidence of this disease, the genetic factors influencing the clinical outcomes of R. equi pneumonia are ill-defined. Here, we performed independent single nucleotide polymorphism (SNP)- and copy number v...
Article
Glycation of recombinant human interferon-gamma (rhIFN-γ) causes conformational alterations of the molecule and results in reduction of its biologic activity. The aim of this study was to find adequate approaches for prevention of glycation in order to obtain a stable recombinant protein with sustained biologic activity. To this end we investigated...
Article
Full-text available
The aim of this study was to analyze the frequency of occurrence of individual stop codons and combinations of stop codons with adjacent upstream and downstream triplets in 264 bacterial and 1308 mammalian mitochondrial genomes. For the purpose of this analysis a novel program (Gene Triplet Analysis) was applied. The obtained results indicate that...
Article
There are three types of influenza virus (A, B and C) of which type A causes worldwide epidemics and pandemics, type B causes epidemics and type C is responsible for minor upper respiratory illnesses. Changeability, evolution and adaptation are crucial for influenza virus A to survive. Three times in the last century it has undergone drastic geneti...
Article
Full-text available
The Postgenomic era (the years following 2000) is characterized by the introduction of a new generation of powerful and low-cost DNA sequencing methods that led to the rapid accumulation of sequencing data in the world DNA databases. Hundreds of viral, bacterial, plant and animal (including individual human) genomes have been completely sequenced a...
Article
Full-text available
Segregation of the expression plasmids under non-selective conditions is due to the irregular distribution of the plasmid molecules between the daughter cells during cell division. Thus a heterogeneous population of cells appears in which the non-productive plasmid-free cells overgrow the plasmid-bearing once. The main factors that influence plasmi...
Article
Glycation is a condensation reaction between reducing sugars and primary amino groups in proteins. It starts with formation of Schiff bases and Amadori products (called early glycation products), which are later converted into complex heterocyclic compounds designated as advanced glycation end (AGE) products. Until recently glycation was studied ma...
Article
The effect of temperature, mechanical stress and surface tension on fluorescence and biological activity of recombinant human interferon gamma (rhIFN-γ) was studied. All three physical factors caused a similar decrease of fluorescence intensity and biological activity, the latter being more strongly affected—a 10–15% fall of fluorescence intensity...
Article
Full-text available
Simple, fast and low cost method for isolation of plasmid DNA, affordable for any laboratory is presented. The method is based on the specific adsorption of double stranded (ds) DNA on glass fibers in the presence of high concentration of guanidine hydrochloride (GnHCl) and elution of the retained DNA with ordinary buffers. Among the various types...
Article
Full-text available
Glycation is a non-emzymatic reaction between free amino groups and reducing sugars (16), which was shown to take place also in human (13). It causes severe complications in diabetic and uremic patients, whereas in normal subjects contributes to senescence and aging. This study points to another negative aspect of glycation concerning the quality o...
Article
Full-text available
Advances in DNA sequencing led to accumulation of genomic data of a great number of prokaryotes belonging to different taxons. In this study we have analyzed 158 prokaryotic genomes for codon usage specificity. The latter is studied not only on the level of the whole genome (all genes) but also for three gene subsets: highly expressed genes, riboso...