Jeevan Giddaluru

Hospital Israelita Albert Einstein | IIEPAE · Israel Institute of Education and Research

Immunological programing of immune cells varies in response to changing environmental signals. This process is facilitated by modifiers that regulate the translational fate of mRNAs encoding various immune mediators, including cytokines and chemokines, which in turn determine the rapid activation, tolerance, and plasticity of the immune system. RNA...

Dengue Viruses (DENVs) cause one of the most prevalent arthropod-borne viral diseases affecting millions of people worldwide. Identification of genes involved in DENV pathogenesis would help in deciphering molecular mechanisms responsible for the disease progression. Here, we carried out a meta-analysis of publicly available gene expression data of...

Rheumatoid arthritis (RA), a symmetric polyarticular arthritis, has long been feared as one of the most disabling forms of arthritis. Identification of gene signatures associated with RA onset and progression would lead toward development of novel diagnostics and therapeutic interventions. This study was undertaken to identify unique gene signature...

The application of nanotechnology in vaccinology have fuelled rapid advancement towards design and development of nanovaccines. Nanoparticles have been found to enhance the vaccine efficacy through the spatiotemporal orchestration of antigen delivery to secondary lymphoid organs and antigen-presentation by Antigen Presenting Cells (APCs) synchroniz...

Activation of the amino acid starvation response (AAR) increases lifespan and acute stress resistance as well as regulates inflammation. However, the underlying mechanisms remain unclear. Here, we show that activation of AAR pharmacologically by Halofuginone (HF) significantly inhibits production of the proinflammatory cytokine interleukin 1β (IL-1...

Objective This study aimed to present a temporal and spatial analysis of the 2018 measles outbreak in Brazil, particularly in the metropolitan city of Manaus in the Amazon region, and further introduce a new tool for spatial analysis. Methods We analyzed the geographical data of the residences of over 7,000 individuals with measles in Manaus durin...

Objective Public health research frequently requires the integration of information from different data sources. However, errors in the records and the high computational costs involved make linking large administrative databases using record linkage (RL) methodologies a major challenge. We present Tucuxi-BLAST, a versatile tool for probabilistic R...

Background Public health research frequently requires the integration of information from different data sources. However, errors in the records and the high computational costs involved make linking large administrative databases using record linkage (RL) methodologies a major challenge. Methods We present Tucuxi-BLAST, a versatile tool for proba...

The current COVID-19 pandemic has already claimed more than 3.7 million victims and it will cause more deaths in the coming months. Tools that track the number and locations of cases are critical for surveillance and help in making policy decisions for controlling the outbreak. However, the current surveillance web-based dashboards run on proprieta...

Background & aims Obesity is associated with low grade systemic inflammation and insulin resistance. Although metabolic and immunological changes may contribute to the increased risk for COVID-19 mortality in obese, little is known about the impact of obesity in the lungs of patients with COVID-19. Methods We analyzed gene expression profiles of a...

Background The progression and severity of COVID-19 varies significantly in the population. While the hallmarks of SARS-CoV-2 and severe COVID-19 within routine laboratory parameters are emerging, the impact of sex and age on these profiles is still unknown. Methods We performed multidimensional analysis of millions of records of laboratory parame...

The structure and function of the immune system is governed by complex networks of interactions between cells and molecular components. Vaccination perturbs these networks, triggering specific pathways to induce cellular and humoral immunity. Systems vaccinology studies have generated vast data sets describing the genes related to vaccination, moti...

Nutrient sensor GCN2 plays a crucial role in the maintenance of cellular homeostasis during the condition of amino acid deprivation. Dysfunction in the GCN2 signaling underlies several chronic metabolic diseases. Recent studies highlight the anti-viral potential of GCN2 against RNA viruses such as Sindbis and HIV. However, its effect on dengue viru...

Introduction: The progression and severity of the coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), varies significantly in the population. While the hallmarks of SARS-CoV-2 and severe COVID-19 within routine laboratory parameters are emerging, little is known abo...

The current COVID-19 pandemic has already claimed more than 100,000 victims and it will cause more deaths in the coming months. Tools that can track the number and locations of cases are critical for surveillance and can help in making policy decisions for controlling the outbreak. The current surveillance web-based dashboards run on proprietary pl...

Immune cells sense and programme its cellular machinery appropriately to the environmental changes through the activation of cytoprotective adaptive pathway so‐called the “integrated stress response (ISR)”. However, the mechanisms implicated in ISR‐induced protective responses are poorly understood. Here, we show that ISR activation by arsenite (Ar...

Ulcerative colitis (UC) is a persistent inflammatory illness, which is clinically categorised as Inflammatory bowel disease (IBD), affecting millions of people worldwide. The precise cause behind the pathology of the disease remains unknown. However, the involvement of multiple factors including genetic predisposition, immunological deregulations,...

HF induces SG formation in BMDMs. Immunofluorescence imaging of SGs (indicated by white arrows) in BMDMs left untreated (media) or treated with HF (20 nM) at time points specified. Scale bars, 5μm. Data are representative of 1 of 4 independent experiments. BMDM, bone marrow–derived macrophage; HF, Halofuginone; SG, stress granule. (TIF)

HF promotes induction of autophagy. (A) LPS-primed or -unprimed J774A.1 macrophages were treated with HF for 6 h in presence or absence of autophagy inhibitor CQ; lysates were assayed for the expression of autophagy proteins LC3-I and LC3-II by immunoblotting. β-actin was used as loading control. (B) p62 expression in macrophages treated with HF in...

GEO data sets used for the meta-analysis study. The table summarizes information of the GEO data sets containing UC and CD patient samples. The table also includes the sample source and the number of control samples. CD, Crohn’s disease; GEO, Gene Expression Omnibus; UC, ulcerative colitis. (XLSX)

Decreased GCN2–eIF2 signaling and RBPs (TIA-1/TIAR) in macrophages result in increased IL-1β production in response to LPS stimulation, and reduced responsiveness to HF treatment. (A) J774A.1 macrophages were transfected with control siRNA- or GCN2-specific siRNA. After 24 h, cell lysates were prepared and analyzed for GCN2 expression by western bl...

Meta-analysis of gene expression data sets reveals differential expression of GCN2 in PBMCs and colon samples from patients with UC and CD. (A) Pipeline of individual gene expression data set analysis followed by meta-analysis. (B) Heat map (left) representing 4,038 DEGs that were commonly expressed across the 5 data sets, in which GCN2 is down-reg...

List of primers used for site-directed mutagenesis. Three different sets of primers given in the table were designed to amplify the entire sequence of the pCMV6-IL-1β plasmid except the 3 regions enriched with AT sequences to be deleted. The primers were designed in such a way that the first mutant plasmid serves as a template to generate the secon...

HF suppresses IL-1β production in LPS-primed macrophages. (A) Mouse BMDMs were primed with LPS (500 ng/ml), followed by HF stimulation for the indicated times; ATP (5mM) was added to the cultures for 30 min prior to harvest. IL-1β levels were measured by ELISA (S1 Data). ***P <0.001 (two-way ANOVA and Bonferroni post-test). (B) Analysis of producti...

List of mouse gene-specific primers. The primer sequences listed in the table were used to examine the analysis of gene expression of various genes. (XLSX)

HF is not toxic to cells at concentrations below 40 nM. Mouse macrophages primed with LPS or left unstimulated were cultured with HF at different concentrations as indicated for 6 h, 12 h, and 24 h. Percent viable cells were assayed by using MTT (S1 Data). Data are representative of 1 of 3 independent experiments. HF, Halofuginone; MTT, 3-(4,5-dime...

HF reduces IL-1β and IL-18 mRNA levels. (A) qRT-PCR analysis of proinflammatory cytokines IL-18, TNF-α, and IL-6 in BMDMs stimulated with LPS or LPS plus HF (S1 Data). (B) IL-1β mRNA levels in HEK293T cells transfected with pCMV6-IL-1β for 36 h followed by treatment with or without Act-D (2 h) and further treatment with HF (20 nM) (S1 Data). *P < 0...

HF-induced effect on IL-1β production is independent of PKR. IL-1β protein levels in the culture supernatant of control siRNA–or PKR siRNA–transfected J774A.1 macrophages, stimulated with LPS (500 ng/ml) followed by stimulation with different concentrations of HF. ATP (5 mM) was added to the cultures for 30 min at the end of the experiment (S1 Data...

LPS-induced TNF-α but not IL-6 transcripts are targeted by the RBPs TIA-1/TIAR during HF treatment. qRT-PCR analysis of IL-6 and TNF-α mRNA in RIP (pull-down using TIA-1/TIAR or IgG) of LPS-primed J774A.1 macrophages untreated or treated with HF (20 nM) (S1 Data). *P < 0.05. Error bars indicate mean ± SEM. Data represent 1 experiment of 3 independe...

HF-induced autophagy controls IL-1β production by targeting SGs for clearance and by controlling mitochondrial ROS. (A) Immunofluorescence microscopy imaging of SGs (stained by TIA-1/TIAR) colocalization with LC3 during HF treatment. Nuclei were stained with DAPI; scale bars, 5 μM. (B) Levels of IL-1β protein in the culture supernatant of control s...