Ilgar Z Mamedov

Ilgar Z Mamedov
Russian Academy of Sciences | RAS · M.M. Shemyakin–Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

PhD

About

132
Publications
20,852
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4,266
Citations
Education
September 1995 - June 2000
Lomonosov Moscow State University
Field of study
  • biochemistry

Publications

Publications (132)
Article
Full-text available
The development and implementation of vaccines have been growing exponentially, remaining one of the major successes of healthcare over the last century. Nowadays, active regular immunizations prevent epidemics of many viral diseases, including tick-borne encephalitis (TBE). Along with the generation of virus-specific antibodies, a highly effective...
Article
Full-text available
We report incidence and deep molecular characteristics of lineage switch in 182 pediatric patients affected by B-cell precursor acute lymphoblastic leukemia (BCP-ALL), who were treated with blinatumomab. We documented six cases of lineage switch that occurred after or during blinatumomab exposure. Therefore, lineage conversion was found in 17.4% of...
Article
Objective One of the current hypotheses to explain the proinflammatory immune response in IBD is a dysregulated T cell reaction to yet unknown intestinal antigens. As such, it may be possible to identify disease-associated T cell clonotypes by analysing the peripheral and intestinal T-cell receptor (TCR) repertoire of patients with IBD and controls...
Article
Full-text available
Retroelements (RE) have been proposed as important players in cancerogenesis. Different cancer types are characterized by a different level of tumor-specific RE insertions. In previous studies, small cohorts of hematological malignancies, such as acute myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia have been characterized by a...
Article
Background. Genomic rearrangements of T and B cell receptor genes (BCR and TCR) have become the gold standard marker for clonality assessment and minimal residual disease monitoring (MRD) in acute lymphoblastic leukemia (ALL). B-ALL can bear both TCR and BCR rearrangements, whereas T-ALL contains mainly TCR rearrangements. The limitation on the num...
Article
Full-text available
The importance of cellular metabolic adaptation in inducing robust T cell responses is well established. However, the mechanism by which T cells link information regarding nutrient supply to clonal expansion and effector function is still enigmatic. Herein, we report that the metabolic sensor adenosine monophosphate‐activated protein kinase (AMPK)...
Preprint
Full-text available
High-throughput sequencing of immune receptor repertoires is a valuable tool for receiving insights in adaptive immunity studies. Several powerful methods for TCR/BCR repertoire reconstruction and analysis have been developed in the past decade. However, detection and correction of the discrepancy between real and experimentally observed lymphocyte...
Article
Full-text available
Haematococcus lacustris is a natural source of a valuable ketocarotenoid astaxanthin. Under autotrophic growth conditions, it exists in the form of a community with bacteria. The close coexistence of these microorganisms raises two questions: how broad their diversity is and how they interact with the microalga. Despite the importance these issues,...
Article
Full-text available
A balanced immune response is a cornerstone of healthy aging. Here, we uncover distinctive features of the long-lived blind mole-rat (Spalax spp.) adaptive immune system, relative to humans and mice. The T-cell repertoire remains diverse throughout the Spalax lifespan, suggesting a paucity of large long-lived clones of effector-memory T cells. Expr...
Article
Full-text available
COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immun...
Article
Full-text available
Background Retroelements (REs) occupy a significant part of all eukaryotic genomes including humans. The majority of retroelements in the human genome are inactive and unable to retrotranspose. Dozens of active copies are repressed in most normal tissues by various cellular mechanisms. These copies can become active in normal germline and brain tis...
Article
Full-text available
The organizational integrity of the adaptive immune system is determined by functionally discrete subsets of CD4 ⁺ T cells, but it has remained unclear to what extent lineage choice is influenced by clonotypically expressed T cell receptors (TCRs). To address this issue, we used a high-throughput approach to profile the ab TCR repertoires of human...
Article
Full-text available
Cancer remains one of the main causes of human mortality despite significant progress in its diagnostics and therapy achieved in the past decade. Massive hypomethylation of retrotransposons, in particular LINE-1, is considered a hallmark of most malignant transformations as it results in the reactivation of retroelements and subsequent genomic inst...
Preprint
Full-text available
COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. The T cell response is a critical part of both individual and herd immunity to SARS-CoV-2 and the efficacy of developed vaccines. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well under...
Conference Paper
Introduction While immunotherapy is highly effective in leukemia, one of the main obstacles to MRD monitoring in ALL patients are CD19- relapses that impede FCM. Detection of clonal rearrangements of Ig/TCR genes is used as a routine method for MRD monitoring along with FCM, and unlike latter is applicable in all immunotherapy patients. Materials a...
Conference Paper
Introduction Clonality assessment using IG/TCR rearrangements is an essential tool for clonal evolution analysis and minimal residual disease monitoring in acute lymphoblastic leukemia (ALL). Here we present a new multiplex method for ALL clonal structures analysis at the single-cell level. Material and Methods: DNA from bone marrow (BM) samples of...
Article
Full-text available
The diverse repertoire of T-cell receptors (TCR) plays a key role in the adaptive immune response to infections. Using TCR alpha and beta repertoire sequencing for T-cell subsets, as well as single-cell RNAseq and TCRseq, we track the concentrations and phenotypes of individual T-cell clones in response to primary and secondary yellow fever immuniz...
Conference Paper
Full-text available
Background and aims: Inflammatory bowel diseases (IBD) are chronic-remittent inflammatory diseases of the gastrointestinal tract. Disease development in IBD is still poorly understood and the search for the causative agents is ongoing. The intestinal inflammation in inflammatory bowel diseases (IBD) is thought to be T cell mediated and therefore de...
Article
Full-text available
Background and aims: Intestinal inflammation in inflammatory bowel diseases (IBD) is thought to be T cell mediated and therefore dependent on the interaction between the T-cell receptor (TCR) and human leukocyte antigen (HLA) proteins expressed on antigen presenting cells.The collection of all TCRs in one individual, known as the TCR repertoire, i...
Preprint
Full-text available
The diverse repertoire of T-cell receptors (TCR) plays a key role in the adaptive immune response to infections. Previous studies show that secondary responses to the yellow fever vaccine - the model for acute infection in humans - are weaker than primary ones, but only quantitative measurements can describe the concentration changes and lineage fa...
Article
Rearrangements of T‐ and B‐cell receptor (TCR and BCR) genes are useful markers for clonality assessment as well as for minimal residual disease (MRD) monitoring during the treatment of haematological malignancies. Currently, rearrangements of three out of four TCR and all BCR loci are used for this purpose. The fourth TCR gene, TRA, has not been u...
Article
Phosphorus (P) is central to storing and transferring energy and information in living cells, including those of microalgae. Many microalgal species dwelling in low P environments are naturally equipped to take up and store P whenever it becomes available through a complex phenomenon known as "luxury P uptake." Its research is required for better u...
Article
Full-text available
Under unfavorable conditions such as host immune responses and environmental stresses, human pathogen Mycobacterium tuberculosis may acquire the dormancy phenotype characterized by “non-culturability” and a substantial decrease of metabolic activity and global transcription rates. Here, we found that the transition of M. tuberculosis from the dorma...
Article
B‐cell receptors and T‐cell receptors are the key molecules responsible for specific antigen recognition in adaptive immunity. The huge diversity of immune receptor repertoires constrained their comprehensive studies in the past. More recently, however, high‐throughput sequencing based techniques have revolutionized the field of immune receptor rep...
Article
Retroelements are considered as one of the important sources of genomic variability in modern humans. It is known that transposition activity of retroelements in germline cells generates new insertions in various genomic loci and sometimes results in genetic diseases. Retroelements activity in somatic cells is restricted by different cellular mecha...
Article
Full-text available
Background There is increasing evidence that the transpositional activity of retroelements (REs) is not limited to germ line cells, but often occurs in tumor and normal somatic cells. Somatic transpositions were found in several human tissues and are especially typical for the brain. Several computational and experimental approaches for detection o...
Preprint
Numerous studies have demonstrated that the percentage of naïve T cells and diversity of T cell receptor (TCR) repertoire decrease with age, with some findings likewise suggesting that increased repertoire diversity may be associated with longer lifespan and healthy aging. In this work, we have analyzed peripheral TCR diversity from humans, mice, a...
Article
Full-text available
Human aging is associated with a profound loss of thymus productivity, yet naïve T lymphocytes still maintain their numbers by division in the periphery for many years. The extent of such proliferation may depend on the cytokine environment, including IL-7 and T-cell receptor (TCR) “tonic” signaling mediated by self pMHCs recognition. Additionally,...
Preprint
Full-text available
T-cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical framework to detect TCR clone proliferation and contraction from longitudinal repertoire data. We applied this framew...
Article
Full-text available
T-cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical framework to detect TCR clone proliferation and contraction from longitudinal repertoire data. We applied this framew...
Article
Full-text available
Autologous hematopoietic stem cell transplantation (HSCT), a safer type of HSCT than allogeneic HSCT, is a promising therapy for patients with severe autoimmune diseases (ADs). Despite the long history of medical practice, structural changes in the adaptive immune system as a result of autologous HSCT in patients with various types of ADs remain po...
Preprint
Full-text available
Background There is increasing evidence that the transpositional activity of retroelements (REs) is not limited to germ line cells, but often occurs in tumor and normal somatic cells. Somatic transpositions were found in several human tissues and are especially typical for the brain. Several computational and experimental approaches for detection o...
Article
Objective: The risk of AS is associated with genomic variants related to antigen presentation and specific cytokine signalling pathways, suggesting the involvement of cellular immunity in disease initiation/progression. The aim of the present study was to explore the repertoire of TCR sequences in healthy donors and AS patients to uncover AS-linke...
Article
Vaccination against influenza is widely used to protect against seasonal flu epidemic although its effectiveness is debated. Here we performed deep quantitative T cell receptor repertoire profiling in peripheral blood of a healthy volunteer in response to trivalent subunit influenza vaccine. We did not observe significant rebuilding of peripheral b...
Article
On the way of understanding the rules and laws of adaptive immunity, high-throughput profiling of TCR repertoires becomes a powerful tool. The structure of TCR repertoires is insightful and instructive even before antigen specificity of each particular receptor becomes available. It embodies information about the thymic and peripheral selection of...
Article
Full-text available
Diverse repertoires of hypervariable immunoglobulin receptors (TCR and BCR) recognize antigens in the adaptive immune system. The development of immunoglobulin receptor repertoire sequencing methods makes it possible to perform repertoire-wide disease association studies of antigen receptor sequences. We developed a statistical framework for associ...
Preprint
Full-text available
Diverse repertoires of hypervariable immunoglobulin receptors (TCR and BCR) recognize antigens in the adaptive immune system. The development of immunoglobulin receptor repertoire sequencing methods makes it possible to perform repertoire-wide disease association studies of antigen receptor sequences. We developed a statistical framework for associ...
Data
Number of shared out-of-frame alpha TCR CDR3 clonotypes reported between all 15 pairs of 6 donors consisting of 3 twin pairs (ordinate) compared to the model prediction (abscissa). To be able to compare datasets of different sizes, the sharing number was normalized by the product of the two cloneset sizes. The outlying three red circles represent t...
Data
Number of shared out-frame beta TCR CDR3 clonotypes reported between all 15 pairs of 6 donors consisting of 3 twin pairs (ordinate) compared to the model prediction (abscissa). The three outlying red circles represent the twin pairs, while the black circles refer to pairs of unrelated individuals. Error bars show one standard deviation. (PDF)
Data
Detailed description of experimental and data analysis procedures and supplementary results. (PDF)
Data
Library preparation protocol. A) cDNA first strand synthesis for alpha and beta chains starts from specific primers in the C-segment conserved region. B) The template switching effect was used to introduce a universal primer binding site to the 3’cDNA end. The SMART-Mk sequence contains a sample barcode (black ellipse) for contamination control. C)...
Data
Number of shared in-frame alpha TCR CDR3 clonotypes reported between all 15 pairs of 6 donors consisting of 3 twin pairs (ordinate) compared to the model prediction (abscissa). To be able to compare datasets of different sizes, the sharing number was normalized by the product of the two cloneset sizes. The three red circles represent the twin pairs...
Data
Number of shared in-frame beta TCR CDR3 clonotypes reported between all 15 pairs of 6 donors consisting of 3 twin pairs (ordinate) compared to the model prediction (abscissa). To be able to compare datasets of different sizes, the sharing number was normalized by the product of the two cloneset sizes. The three outlying red circles represent the tw...
Data
Reproducibility of our results using previously published data. Distribution of Pgen—the probability that a sequence is generated by the VJ recombination process—for shared out-of-frame TCR alpha clonotypes between individual A1 from [8] and the other five individuals. While the distribution of shared sequences between unrelated individuals (red cu...
Data
Normalized sharing of out-of-frame zero insertion clonotypes. Number of shared out-frame alpha zero insertion TCR CDR3 clonotypes reported between all 15 pairs of 6 donors consisting of 3 twin pairs (ordinate) compared to the model prediction (abscissa). The three red circles represent the twin pairs, while the black circles refer to pairs of unrel...
Data
Mean number of insertions in shared sequences in alpha out-of-frame repertoires of CD45RO+ (memory) cells. (PDF)
Data
Dependence of mean insertion number on rank holds for different bin sizes. Mean numbers of insertions were obtained by analysing subsequent groups of 1000 (A) and 4000 (B) sequences of decreasing abundances, as in Fig 3A from the main text. (C,D,E) are results for ageing datasets reproduced for the top 1000, 2000 and 4000 clonotypes. Solid lines ar...
Data
Mean number of insertions in shared sequences in alpha out-of-frame repertoires. (PDF)
Data
The dependence between clone abundance and mean insertion number is robust across cord blood donors. Mean numbers of insertions were obtained by analysing groups of 3000 sequences of decreasing abundances as in Fig 3A, for 7 independent published cord blood samples from [24]. A similar decreasing trend is observed for all samples. (PDF)
Data
Rank-abundance dependencies. Here we show the dependence of the clone abundance on its abundance rank in samples from Fig 3A. Memory clones are typically larger than the naive and cord blood clones of same rank, possibly due to the history of clonal expansions. (PDF)
Data
Number of reads, UMI and unique CDR3 nucleotide sequences in each sample. (XLSX)
Data
Ageing data used for Fig 4 and exponential decay fits. Percentage of the naive T-cells defined using flow cytometry, see [23] for details. (XLSX)
Presentation
Full-text available
Taking up nutrients such as phosphorus (P) in amounts exceeding the demand for supporting cell division in the absence of limitation is termed luxury uptake (LU). Although LU is long known in microalgae and regarded as a promising vehicle for recycling of P from waste streams [1], it remains poorly elucidated. We studied the relationships between c...
Article
Allogeneic transplantation of hematopoietic cells (HSCT) is an established method to treat different hematologic malignancies and disorders of hematopoietic and lymphoid system. Graft-versus-host-disease is one of the main risk factor for success of the procedure. Simultaneous depletion of alpha-beta T-cells and CD19+ cells in graft is the promisin...
Article
αβT-cell depleted allogeneic hematopoietic cells transplantation holds promise for the safe and accessible therapy of both malignant and non-malignant blood disorders. Here we employed molecular barcoding-normalized T-cell receptor (TCR) profiling to quantitatively track T-cell immune reconstitution after TCRαβ/CD19-depleted transplantation in chil...
Article
High-throughput sequencing analysis of hypermutating immunoglobulin (IG) repertoires remains a challenging task. Here we present a robust protocol for the full-length profiling of human and mouse IG repertoires. This protocol uses unique molecular identifiers (UMIs) introduced in the course of cDNA synthesis to control bottlenecks and to eliminate...
Article
Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.