Zohreh Tatari-calderone - Academia.edu (original) (raw)

Papers by Zohreh Tatari-calderone

Additional file 2. Delineation of Covid-19 relevant modules sets in all 17 aggregates retained in... more Additional file 2. Delineation of Covid-19 relevant modules sets in all 17 aggregates retained in the first step of the selection process.

Additional file 3. Composition and annotation of the 382 module repertoire employed as a framewor... more Additional file 3. Composition and annotation of the 382 module repertoire employed as a framework for the selection of targeted Covid-19 blood transcriptional panels. Membership to the 28 Covid-19 module sets is indicated in column D.

Additional file 1: Figure S1. Coverage of the pre-established 38 transcriptional module aggregate... more Additional file 1: Figure S1. Coverage of the pre-established 38 transcriptional module aggregate repertoire by the Nanostring immunology panel 2. The bar graphs show the distribution of the 579 transcript constituting the standard Nanostring immunology panel used by Ong et al. across the 38 module aggregates forming this repertoire. The Venn diagram shows the degree of overlap between the Nanostring panel and the transcripts forming this modular repertoire.

npj Genomic Medicine, 2022

Clinical implementation of pharmacogenomics will help in personalizing drug prescriptions and all... more Clinical implementation of pharmacogenomics will help in personalizing drug prescriptions and alleviate the personal and financial burden due to inefficacy and adverse reactions to drugs. However, such implementation is lagging in many parts of the world, including the Middle East, mainly due to the lack of data on the distribution of actionable pharmacogenomic variation in these ethnicities. We analyzed 6,045 whole genomes from the Qatari population for the distribution of allele frequencies of 2,629 variants in 1,026 genes known to affect 559 drugs or classes of drugs. We also performed a focused analysis of genotypes or diplotypes of 15 genes affecting 46 drugs, which have guidelines for clinical implementation and predicted their phenotypic impact. The allele frequencies of 1,320 variants in 703 genes affecting 299 drugs or class of drugs were significantly different between the Qatari population and other world populations. On average, Qataris carry 3.6 actionable genotypes/dip...

Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to f... more Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells.

F1000Research, 2021

Developing the skills needed to effectively search and extract information from biomedical litera... more Developing the skills needed to effectively search and extract information from biomedical literature is essential for early-career researchers. It is, for instance, on this basis that the novelty of experimental results, and therefore publishing opportunities, can be evaluated. Given the unprecedented volume of publications in the field of biomedical research, new systematic approaches need to be devised and adopted for the retrieval and curation of literature relevant to a specific theme. Here we describe a hands-on training curriculum aimed at retrieval, profiling, and visualization of literature associated with a given topic. This curriculum was implemented in a workshop in January 2021. We provide supporting material and step-by-step implementation guidelines with the ISG15 gene literature serving as an illustrative use case. Through participation in such a workshop, trainees can learn: 1) to build and troubleshoot PubMed queries in order to retrieve the literature associated w...

Transfusion Medicine and Hemotherapy, 2014

Proceedings of the National Academy of Sciences, 1995

We describe a technique for HLA-Cw genotyping by digestion of PCR-amplified genes with restrictio... more We describe a technique for HLA-Cw genotyping by digestion of PCR-amplified genes with restriction endonucleases. Locus-specific primers selectively amplified HLA-Cw sequences from exon 2 in a single PCR that avoided coamplification of other classical and nonclassical class I genes. Amplified DNAs were digested with selected enzymes. Sixty-three homozygous cell lines from International Histocompatibility Workshop X and 113 unrelated individual cells were genotypes for HLA-Cw and compared with serology. The present protocol can distinguish 23 alleles corresponding to the known HLA-Cw sequences. Genotyping of serologically undetectable alleles (HLA-Cw Blank) and of heterozygous cells was made possible by using this method. Six additional HLA-Cw alleles were identified by unusual restriction patterns and confirmed by sequencing; this observation suggests the presence of another family of allele-sharing clusters in the HLA-B locus. This PCR-restriction endonuclease method provides a sim...

Clinical and Developmental Immunology, 2013

The goal of the present work was to identify the candidate genetic markers predictive of alloimmu... more The goal of the present work was to identify the candidate genetic markers predictive of alloimmunization in sickle cell disease (SCD). Red blood cell (RBC) transfusion is indicated for acute treatment, prevention, and abrogation of some complications of SCD. A well-known consequence of multiple RBC transfusions is alloimmunization. Given that a subset of SCD patients develop multiple RBC allo-/autoantibodies, while others do not in a similar multiple transfusional setting, we investigated a possible genetic basis for alloimmunization. Biomarker(s) which predicts (predict) susceptibility to alloimmunization could identify patients at risk before the onset of a transfusion program and thus may have important implications for clinical management. In addition, such markers could shed light on the mechanism(s) underlying alloimmunization. We genotyped 27 single nucleotide polymorphisms (SNPs) in theCD81,CHRNA10,andARHGgenes in two groups of SCD patients. One group (35) of patients devel...

Cancer Immunotherapy Principles and Practice, 2021

This book focuses on converging concepts and peculiarities relevant to the relationship between t... more This book focuses on converging concepts and peculiarities relevant to the relationship between the host and the neoplastic tissue. It aims at guiding the neophyte through a critical interpretation of upcoming results based on a solid understanding of anticancer immunotherapy concepts within the context of alternative treatments and the potential for their combinations. The book is primarily targeted at young basic and clinical investigators but open to all other constituencies. It brings together cutting-edge insight that every translational investigator and practicing clinician needs to know about tumor immunology and immunotherapy. The textbook is divided into five sections. The first section, comprising thirteen chapters, presents the basic principles of tumor immunology such as systems biology of T cells, activation of CD4 + T lymphocytes, regulation of cell-mediated immunity, role of Breg cells in modulating the antitumor immune response, innate immune system, and the role of the tumor microenvironment. The second section, consisting of ten chapters, deals with cancer immunotherapy targets and classes such as cancer vaccines, T cell modulatory cytokines, adoptive T cell transfer, and oncolytic viruses. The next section, comprising fourteen chapters discusses immune function in cancer patients. Section four, consisting of fourteen chapters, presents disease-specific treatments and outcomes such as immunotherapy for melanoma, genitourinary malignancies, gastrointestinal cancers, hepatocellular carcinoma, gynecologic malignancies, breast cancer, lung cancer, head and neck cancer, hematologic malignancies, brain tumors, sarcomas, and pediatric cancers. The final section discusses the regulatory aspects of cancer immunotherapy covering chemistry, manufacturing and control, and preclinical and clinical considerations for cell therapy and gene therapy-based immunotherapy products for human clinical trials, and regulatory considerations for in vitro diagnostic devices. In addition, the book also presents a chapter on the history of immunotherapy.

Frontiers in Immunology

Transcriptome profiling approaches have been widely used to investigate the mechanisms underlying... more Transcriptome profiling approaches have been widely used to investigate the mechanisms underlying psoriasis pathogenesis. Most researchers have measured changes in transcript abundance in skin biopsies; relatively few have examined transcriptome changes in the blood. Although less relevant to the study of psoriasis pathogenesis, blood transcriptome profiles can be readily compared across various diseases. Here, we used a pre-established set of 382 transcriptional modules as a common framework to compare changes in blood transcript abundance in two independent public psoriasis datasets. We then compared the resulting “transcriptional fingerprints” to those obtained for a reference set of 16 pathological or physiological states. The perturbations in blood transcript abundance in psoriasis were relatively subtle compared to the changes we observed in other autoimmune and auto-inflammatory diseases. However, we did observe a consistent pattern of changes for a set of modules associated ...

The Journal of …, 2002

The interaction between CD28 on T cells and CD80 on APCs intensifies the linkage between TCR and ... more The interaction between CD28 on T cells and CD80 on APCs intensifies the linkage between TCR and MHC at the site of contact between T cells and APCs. In this study, we demonstrate that during human T cell/human APC interaction, the autologous or allogeneic human CD4 ؉ T cells become positive for the detection of CD80 at an early stage of activation (24 h). This detection of CD80 is attributable to the acquisition of CD80 from APCs, as opposed to the up-regulation of endogenous CD80, as demonstrated by CD4 ؉ T cells treated with cyclohexamide. Furthermore, no CD80 mRNA could be detected at 24 h in T cells that had acquired CD80 from APCs. CD80 acquisition by T cells from APCs was enhanced upon TCR engagement. The amount of CD80 acquisition by CD4 ؉ T cells was shown to be related to the expression of CD80 on APCs. Using soluble fusion proteins (soluble CTLA-4, CD28, and CD80) to block either CD28 on the surface of T cells or CD80 on the surface of APCs, it was demonstrated that CD80 acquisition by T cells is mediated through its receptors, possibly CD28 interaction. Moreover, we demonstrate that T cells that have acquired CD80 have the ability to stimulate other T cells. These data thus suggest that CD80 acquisition by human T cells might play a role in the immunoregulation of T cell responses.

Scientific Reports

To describe the clinical features, epidemiology, autoantibody status, HLA haplotypes and genetic ... more To describe the clinical features, epidemiology, autoantibody status, HLA haplotypes and genetic mechanisms of type 1 diabetes mellitus (T1DM). Patients (0–18 years) with diabetes were recruited. Clinical data was collected, autoantibodies and c-peptide were measured. Whole Genome Sequencing was performed. Genomic data analysis was compared with the known genes linked with T1DM and HLA alleles were studied. 1096 patients had one or more antibody positivity. The incidence of T1DM in 2020 was 38.05 per 100,000 children and prevalence was 249.73. GADA was the most common autoantibody followed by IAA. Variants in GSTCD, SKAP2, SLC9B1, BANK1 were most prevalent. An association of HLA haplotypes DQA1*03:01:01G (OR = 2.46, p value = 0.011) and DQB1*03:02:01G (OR = 2.43, p value = 0.022) was identified. The incidence of T1DM in Qatar is the fourth highest in the world, IA2 autoantibody was the most specific with some patients only having ZnT8 or IA2 autoantibodies thus underlining the neces...

Background: Covid-19 morbidity and mortality are associated with a dysregulated immune response. ... more Background: Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of focused blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. Methods: We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. Results: As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: immunological relevance, therapeutic development relevance and SARS biology relevance. Conclusion: Altogether the work presented here may contribute to th...

Scientific Reports, 2015

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this ... more Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over 7 times more likely to have Stage III disease (p = 0.011; OR = 7.13, (95% CI 1.56-32.52). Neonates with TGFβ-1 (rs2241712) had a decreased incidence of NEC-related perforation (p = 0.044; OR = 0.28, 95% CI: 0.08-0.97) and an increased incidence of mortality (p = 0.049; OR = 2.99, 95% CI: 1.01-8.86). TRIM21 (rs660) was associated with NEC-related intestinal perforation (p = 0.038; OR = 4.65, 95% CI 1.09-19.78). In premature Caucasian neonates, the functional SNP IL-6 (rs1800795) is associated with both the development and increased severity of NEC. TRIM21 (rs660) and TGFβ-1 (rs2241712) were associated with NEC-related perforation in all neonates in the cohort. These findings suggest a possible genetic role in the development of NEC. Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality among preterm neonates 1,2. Its prevalence has increased over the last 30 years as advances in neonatal critical care have led to improved survival of more preterm neonates. In fact, a recent study looking at mortality among extremely premature neonates between 2000-2011, noted that although overall mortality among this population has declined, deaths related to NEC have increased 3. There is an overall mortality rate of 20-30% in infants with NEC and approaches 100% in neonates with pan-intestinal disease (NEC totalis) 4. The onset of NEC is variable, and is inversely proportional to gestational age 5. Signs and symptoms of the disease are often non-specific and require a high index of suspicion. The diagnosis of NEC is made using specific criteria as classified by the Modified Bell Staging (Table 1) 6,7 .

Human immunology, Jan 15, 2015

Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is conside... more Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT-HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression. While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p=0.02), -DQ3 (p=0.02) and -DQ5 (p=0.01) alleles were significantly hig...

Purpose The current method of obtaining DNA for genetic evaluation in Very Low Birthweight infant... more Purpose The current method of obtaining DNA for genetic evaluation in Very Low Birthweight infants requires obtaining a blood sample. In these premature neonates, every milliliter of blood drawn is significant in terms of their total blood volume. It is the purpose of this study to evaluate if a non-invasive test can be used as a substitute to obtain enough high-quality DNA to perform genetic analysis including single nucleotide polymorphism (SNP) genotyping, evaluation of copy number variants, and exome sequencing. We hypothesize that genetic analysis of premature infants with a non-invasive test, specifically a buccal swab, results in sufficient, high quality DNA to determine their genotype for a SNP associated with a hyper-immune state. Methods Patients were prospectively recruited if they were admitted to the NICU at less than 34 weeks gestation, or transferred in with a diagnosis of necrotizing enterocolitis (NEC). Patients were excluded if they had congenital heart disease (ex...