DR37 DataRelease

SDY1599: Synovial fibroblast positional identity controlled by inductive Notch signaling underlies pathologic damage in inflammatory arthritis
Status: New
Description: The synovium is a mesenchymal tissue composed mainly of fibroblasts with a lining and sublining that surrounds the joints. In rheumatoid arthritis (RA), the synovial tissue undergoes marked hyperplasia, becomes inflamed and invasive and destroys the joint1,2. Recently, we and others found that a subset of fibroblasts located in the sublining undergoes major expansion in RA and is linked to disease activity 35. However, the molecular mechanism by which these fibroblasts expand in RA remains unknown. Here, we identified a critical role for NOTCH3 signaling in the differentiation of perivascular and sublining CD90(THY1)+ fibroblasts. Using single cell RNA-sequencing and mixed cell micromass organoids, we found that NOTCH3 signaling drives both transcriptional and spatial gradients in fibroblasts emanating from vascular endothelial cells outward. In active RA, NOTCH3 and NOTCH target genes are markedly upregulated in synovial fibroblasts. Importantly, genetic deletion of Notch3 or monoclonal antibody-blockade of NOTCH3 signaling attenuates inflammation and prevents joint damage in inflammatory arthritis. Our results indicate that synovial fibroblasts exhibit positional identity regulated by endothelium-derived Notch signaling and that this stromal crosstalk pathway underlies inflammation and pathology in inflammatory arthritis.
Program/Contract:
ProgramContract
NIH Program Cadherin 11 Regulates Synovial Inflammation In Arthritis
NIH Program Discovery And Functional Impact Of Common And Rare Variants In RA
DOI: 10.21430/M3R2HHAQ4Q
Subjects: 32
Study PI, contact:
NameOrganizationSite
Publications:
Notch signalling drives synovial fibroblast identity and arthritis pathology.. Nature Jun 2020. doi: 10.1038/s41586-020-2222-z [Pubmed: 32499639]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
RNA sequencing 68
Clinical Assessments:None
SDY1619: Study of Safety and Effectiveness of Intravenous Immunization With PfSPZ Vaccine in Healthy African Adults - Vaccine Safety Cohort
Status: New
Description: Plasmodium falciparum sporozite (PfSPZ) Vaccine is a metabolically active, non-replicating, whole malaria sporozoite vaccine that has been reported to be safe and protective against P falciparum controlled human malaria infection in malaria-naive individuals. We aimed to assess the safety and protective efficacy of PfSPZ Vaccine against naturally acquired P falciparum in malaria-experienced adults in Mali. After an open-label dose-escalation study in a pilot safety cohort, we did a double-blind, randomised, placebo controlled trial based in Doneguebougou and surrounding villages in Mali. We recruited 18-35 year old healthy adults who were randomly assigned (1:1) in a double-blind manner, with stratification by village and block randomisation, to receive either five doses of 2.7x10^5 PfSPZ or normal saline at days 1, 29, 57, 85, and 141 during the dry season (January to July inclusive). Participants and investigators were masked to group assignments, which were unmasked at the final study visit, 6 months after receipt of the last vaccination. Participants received combined artemether and lumefantrine (four tablets, each containing 20 mg artemether and 120 mg lumefantrine, given twice per day over 3 days for a total of six doses) to eliminate P falciparum before the first and last vaccinations. We collected blood smears every 2 weeks and during any illness for 24 weeks after the fifth vaccination. The primary outcome was the safety and tolerability of the vaccine, assessed as local and systemic reactogenicity and adverse events. The sample size was calculated for the exploratory efficacy endpoint of time to first P falciparum infection beginning 28 days after the fifth vaccination. The safety analysis included all participants who received at least one dose of investigational product, whereas the efficacy analyses included only participants who received all five vaccinations.
Program/Contract:
ProgramContract
NIH Program Genome-Wide Sieve Analysis And Immunological Validation To Identify Targets Of Protective Efficacy In Field Trials Of A Whole-Organism Malaria Vaccine
DOI: 10.21430/M3UCU1AZLC
Subjects: 12
Study PI, contact:
NameOrganizationSite
Sara Healy NIAID Laboratory of Malaria Immunology and Vaccinology NIAID Laboratory of Malaria Immunology and Vaccinology
Patrick Duffy NIAID Laboratory of Malaria Immunology and Vaccinology NIAID Laboratory of Malaria Immunology and Vaccinology
Publications:
Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial.. The Lancet. Infectious diseases May 2017. doi: 10.1016/S1473-3099(17)30104-4 [Pubmed: 28216244]
Resources:
ClinicalTrials.Gov https://clinicaltrials.gov/ct2/show/NCT01988636]
Assays:None
Clinical Assessments:None
SDY1631: The roles of CD103 and CD49a in adherence and motility of CD8 T cells
Status: New
Description: Tissue resident memory CD8 T (TRM) cells are a unique immune memory subset that develops and remains in peripheral tissues at the site of infection, providing future host resistance upon re-exposure to that pathogen. In the pulmonary system, TRM are identified through S1P antagonist CD69 and expression of integrins CD103/_7 and CD49a/CD29(_1). Contrary to the established role of CD69 on CD8 T cells, the functions of CD103 and CD49a on this population are not well defined. This study examines the expression patterns and functions of CD103 and CD49a with a specific focus on their impact on T cell motility during influenza virus infection. We show that the TRM cell surface phenotype develops by two-weeks post-infection and that each integrin contributes a distinct function regulating CD8 T cell motility both in vitro and in vivo, with CD49a facilitating migration and CD103 limiting motility through tethering. These results demonstrate for the first time how CD103 and CD49a differentially impact adherence and migration in the tissue, likely affecting overall retention, maintenance of TRM, and host protection.
Program/Contract:
ProgramContract
Respiratory Pathogens Research Center (RPRC) Respiratory Pathogens Research Center (RPRC)
DOI: 10.21430/M3IV53ZSX3
Subjects: 12
Study PI, contact:
NameOrganizationSite
David Topham University of Rochester University of Rochester CVBI
Publications:None
Resources:
Assays:
Assay TypeNumber of Exp. Samples
Flow Cytometry 136
Microscopy 28
Clinical Assessments:None
SDY1646: 43rd Multicenter Airway Research Collaboration (MARC-43)
Status: New
Description: We enrolled healthy infants from a primary care group practice from November 2013 through May 2014. Fecal samples were collected via a standardized protocol at home before the clinic visit. First, diapers containing feces were refrigerated or stored in a cooler by parents immediately after collection. The fecal samples were then placed in sterile Sarstedt feces collection containers and immediately stored at _80C. Frozen samples were shipped on dry ice to Baylor College
Program/Contract:
ProgramContract
NIAID Program Research Project Grant (Parent R01) Prospective Cohort Study Of Severe Bronchiolitis And Risk Of Recurrent Wheezing (MARC-35 WIND)
DOI: 10.21430/M3UNSL0593
Subjects: 0
Study PI, contact:
NameOrganizationSite
Carlos A. Camargo Massachusetts General Hospital Massachusetts General Hospital
Publications:
The Fecal Microbiota Profile and Bronchiolitis in Infants.. Pediatrics Jul 2016. doi: 10.1542/peds.2016-0218 [Pubmed: 27354456]
Resources:
Assays:None
Clinical Assessments:None
SDY1671: Study of Safety and Effectiveness of Intravenous Immunization With PfSPZ Vaccine in Healthy African Adults - Vaccine Efficacy and Placebo Cohorts
Status: New
Description: Plasmodium falciparum sporozite (PfSPZ) Vaccine is a metabolically active, non-replicating, whole malaria sporozoite vaccine that has been reported to be safe and protective against P falciparum controlled human malaria infection in malaria-naive individuals. We aimed to assess the safety and protective efficacy of PfSPZ Vaccine against naturally acquired P falciparum in malaria-experienced adults in Mali. After an open-label dose-escalation study in a pilot safety cohort, we did a double-blind, randomised, placebo controlled trial based in Doneguebougou and surrounding villages in Mali. We recruited 18-35 year old healthy adults who were randomly assigned (1:1) in a double-blind manner, with stratification by village and block randomisation, to receive either five doses of 2.7x10^5 PfSPZ or normal saline at days 1, 29, 57, 85, and 141 during the dry season (January to July inclusive). Participants and investigators were masked to group assignments, which were unmasked at the final study visit, 6 months after receipt of the last vaccination. Participants received combined artemether and lumefantrine (four tablets, each containing 20 mg artemether and 120 mg lumefantrine, given twice per day over 3 days for a total of six doses) to eliminate P falciparum before the first and last vaccinations. We collected blood smears every 2 weeks and during any illness for 24 weeks after the fifth vaccination. The primary outcome was the safety and tolerability of the vaccine, assessed as local and systemic reactogenicity and adverse events. The sample size was calculated for the exploratory efficacy endpoint of time to first P falciparum infection beginning 28 days after the fifth vaccination. The safety analysis included all participants who received at least one dose of investigational product, whereas the efficacy analyses included only participants who received all five vaccinations.
Program/Contract:
ProgramContract
NIH Program Genome-Wide Sieve Analysis And Immunological Validation To Identify Targets Of Protective Efficacy In Field Trials Of A Whole-Organism Malaria Vaccine
DOI: 10.21430/M3XAASI63D
Subjects: 93
Study PI, contact:
NameOrganizationSite
Sara Healy NIAID Laboratory of Malaria Immunology and Vaccinology NIAID Laboratory of Malaria Immunology and Vaccinology
Patrick Duffy NIAID Laboratory of Malaria Immunology and Vaccinology NIAID Laboratory of Malaria Immunology and Vaccinology
Publications:
Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial.. The Lancet. Infectious diseases May 2017. doi: 10.1016/S1473-3099(17)30104-4 [Pubmed: 28216244]
Resources:
ClinicalTrials.Gov https://clinicaltrials.gov/ct2/show/NCT01988636]
Assays:None
Clinical Assessments:None
SDY1679: Relaxed constraint and functional divergence of PGR
Status: New
Description: To resolve existing conflicting data on progesterone receptor gene (PGR) evolution, the study assembled a dataset of 119 Eutherian PGRs and used a suite of maximum likelihood-based methods to characterize the strength and direction of selection acting on PGR. The result shows that PGR evolved rapidly in the human lineage (as well as other Catarrhine primates), which likely reflects an episode of relaxed selection intensity rather than positive selection. Coincident with the episode of relaxed selection intensity, ancestral sequence resurrection and functional tests indicate that the major human PR isoforms (PR-A and PR-B) evolved divergent functions in the human stem-lineage. These results suggest that the regulation of progesterone signaling by PR-A and PR-B may also have diverged in the human lineage and that non-human animal models of progesterone signaling may not faithfully recapitulate human biology
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M3SB6G69P1
Subjects: 0
Study PI, contact:
NameOrganizationSite
Vincent Lynch University at Buffalo Department of Biological Sciences
Publications:
Relaxed constraint and functional divergence of the progesterone receptor (PGR) in the human stem-lineage.. PLoS genetics Apr 2020. doi: 10.1371/journal.pgen.1008666 [Pubmed: 32302297]
Resources:
paper https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008666]
Assays:None
Clinical Assessments:None
SDY1680: Flow Cytometry of T cells from HAARVI COVID-19 Cohort
Status: New
Description: Intracellular Cytokine Staining data and Surface Marker Phenotyping data from convalescent COVID-19 infected individuals who were previously either hospitalized or not hospitalized. Both the magnitude and functional breadth of antigen-specific CD4 T cell responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. CD4 T cell responses to all antigens were driven by IFN-?-independent poyfunctional profiles that are not typically the focus of vaccine studies.
Program/Contract:
ProgramContract
NIH Program Qualification Of Assays To Measure Human T-Cell Responses Against Mycobacterial Lipid Antigens
DOI: 10.21430/M3OCS4VQWY
Subjects: 68
Study PI, contact:
NameOrganizationSite
Publications:
None. None None None. doi: None [Pubmed: TBD]
Resources:
Github github.com/seshadrilab]
Assays:
Assay TypeNumber of Exp. Samples
Flow Cytometry 457
Clinical Assessments:None
SDY1681: Endometrial Gland Organoids
Status: New
Description: The study established endometrial gland organoids from decidua isolated from term placental membranes. These organoids express typical markers of glandular epithelia such as E-cadherin, Laminin and Cytokeratin 7, and can be propagated in cell culture through multiple passages. Potential survival factors for the co-culture of organoids and endometrial stromal fibroblasts were identified. These modifications facilitate the generation of patient-specific endometrial gland organoids with known pregnancy outcomes
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M3H8HWJ1IC
Subjects: 0
Study PI, contact:
NameOrganizationSite
Vincent Lynch University at Buffalo Department of Biological Sciences
Publications:
Derivation of endometrial gland organoids from term placenta.. Placenta Nov 2020. doi: 10.1016/j.placenta.2020.08.017 [Pubmed: 32937244]
Resources:
RNAseq_GSE157380 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE157380]
SRA_trace_PRJNA661086 https://www.ncbi.nlm.nih.gov/Traces/study/?acc=PRJNA661086]
paper_link https://www.sciencedirect.com/science/article/pii/S0143400420302782]
Assays:None
Clinical Assessments:None
SDY1683: PLA2G6 in attenuating ferroptosis
Status: New
Description: The study found that spontaneous preterm birth (SPTB) is associated with ferroptosis and that inhibition of GPX4 causes ferroptotic injury in primary human trophoblasts and during mouse pregnancy. Importantly, the role for the phospholipase PLA2G6, known to metabolize Hp-PE to lyso-PE and oxidized fatty acid, was uncovered in mitigating ferroptosis induced by GPX4 inhibition in vitro or by hypoxia/reoxygenation injury in vivo. Together, ferroptosis signaling and the role for PLA2G6 in attenuating trophoblastic ferroptosis in the human and mouse placenta was identified, which provided mechanistic insights into the ill-defined placental lipotoxicity that may inspire PLA2G6-targeted therapeutic strategies
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M3KAQ17AWD
Subjects: 0
Study PI, contact:
NameOrganizationSite
Yoel Sadovsky University of Pittsburgh Magee-Womens Research Institute
Publications:
PLA2G6 guards placental trophoblasts against ferroptotic injury.. Proceedings of the National Academy of Sciences of the United States of America Oct 2020. doi: 10.1073/pnas.2009201117 [Pubmed: 33087576]
Resources:
33087576_supplDocu https://www.pnas.org/content/pnas/suppl/2020/10/21/2009201117.DCSupplemental/pnas.2009201117.sapp.pdf]
RNAseq_GSE147625 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE147625]
PRJNA615850 https://www.ncbi.nlm.nih.gov/bioproject/PRJNA615850]
Assays:None
Clinical Assessments:None
SDY1684: Clinical Immunology of Infant Macaques
Status: New
Description: We collected and analyzed blood samples from 151 healthy rhesus
Program/Contract:
ProgramContract
NIH Program Monocyte/Macrophages In Pediatric AIDS
NIH Program Targeting Macrophage Reservoirs In The Macaque Model Of Pediatric AIDS
DOI: 10.21430/M3W5PX1Q02
Subjects: 143
Study PI, contact:
NameOrganizationSite
Marcelo Kuroda Division of Immunology, Tulane National Primate Research Center Tulane National Primate Research Center
Publications:
Clinical and Immunological Metrics During Pediatric Rhesus Macaque Development.. Frontiers in pediatrics Jul 2020. doi: 10.3389/fped.2020.00388 [Pubmed: 32766187]
Resources:
Assays:None
Clinical Assessments:None
SDY1686: Dissecting maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes, and adult phenotypes
Status: New
Description: Based on 10,734 mother?infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, the study constructed haplotype genetic scores using SNPs known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). And tested associations between these haplotype genetic scores and birth outcomes (gestational duration, birth weight). In addition, constructed the infant-specific birth weight genetic scores to examine the effects of fetal growth on gestational duration and maternal phenotypes during pregnancy. The conclusions of the study are that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M3PC6GT19O
Subjects: 0
Study PI, contact:
NameOrganizationSite
Ge Zhang University of Cincinnati College of Medicine Division of Human Genetics
Publications:
Dissecting maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes, and adult phenotypes: A mendelian-randomization and haplotype-based genetic score analysis in 10,734 mother-infant pairs.. PLoS medicine Aug 2020. doi: 10.1371/journal.pmed.1003305 [Pubmed: 32841251]
Resources:
source_DNBC_dbGAP https://www.ncbi.nlm.nih.gov/gap/advanced_search/?TERM=phs000103.v1.p1]
source_HAPO_dbGAP https://www.ncbi.nlm.nih.gov/gap/advanced_search/?TERM=phs000096.v4.p1]
source_GPN_dbGAP https://www.ncbi.nlm.nih.gov/gap/advanced_search/?TERM=phs000714.v1.p1]
source_FIN http://prematurityresearch.org/ohiocollaborative]
source_MoBa https://www.fhi.no/en/studies/moba/for-forskere-artikler/research-and-data-access]
source_ALSPAC http://www.bristol.ac.uk/alspac/researchers/access]
ALSPAC_dataSharingPlan http://www.bristol.ac.uk/alspac/researchers/data-access/documents/alspac-data-management-plan.pdf]
paper_link https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003305]
Assays:None
Clinical Assessments:None
SDY1688: Computational discovery of therapeutic candidates for preventing preterm birth
Status: New
Description: Few therapeutic methods exist for preventing preterm birth (PTB). In the US, progesterone (P4) supplementation is the only FDA-approved drug for use in preventing recurrent spontaneous PTB. However, P4 has limited effectiveness (only 1/3 of cases). To identify repositioning drug candidates, the study used a rank-based pattern-matching strategy to compare the differential gene expression signature for PTB to differential gene expression drug profiles in the Connectivity Map database and assigned a reversal score to each PTB-drug pair. Eighty-three drugs, including P4, were identified. Many of these compounds have been evaluated in the context of pregnancy, with 13 belonging to pregnancy category A or B ? indicating no known risk in human pregnancy. The drug lansoprazole (a proton-pump inhibitor) with a strong reversal score and a good safety profile was selected for validation in LPS-induced inflammation mouse model. The result showed a significant increase in fetal viability by lansoprazole compared with controls
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M3NWW7IS3O
Subjects: 0
Study PI, contact:
NameOrganizationSite
Marina Sirota University of California, San Francisco Bakar Computational Health Sciences Institute and Department of Pediatrics
Publications:
Computational discovery of therapeutic candidates for preventing preterm birth.. JCI insight Feb 2020. doi: 10.1172/jci.insight.133761 [Pubmed: 32051340]
Resources:
SDY1327_transcriptome https://www.immport.org/shared/study/SDY1327]
source_GSE46510 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46510]
source_GSE59491 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59491]
source_GSE73685 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE73685]
Ref: computational drug repurposing pipeline https://github.com/Bin-Chen-Lab/HCC_NEN]
Cmap_source_GSE70138 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70138]
Drugbank www.drugbank.ca]
Assays:None
Clinical Assessments:None
SDY1692: High-throughput quantitation of serological ceramides/dihydroceramides by LC/MS/MS
Status: New
Description: The study developed the LC/MS/MS assay to quantify 16 ceramides and 10 dihydroceramides in human serum within 5 minutes. Validated the assay results against a set of quality criteria in FDA guidelines: Lower Limit of Quantitation (1 nM), linearity (R2>0.99), precision (imprecision<15 %), accuracy (inaccuracy<15 %), extraction recovery (>90 %), stability (>85 %), and carryover (<0.01 %). With enhanced sensitivity and specificity, the study established gestation baselines of ceramides and dihydroceramides in pregnancy
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M3WBUTVTO4
Subjects: 0
Study PI, contact:
NameOrganizationSite
Xuefeng Ling Stanford University School of Medicine Clinical and Translational Research Program
Publications:
High-throughput quantitation of serological ceramides/dihydroceramides by LC/MS/MS: Pregnancy baseline biomarkers and potential metabolic messengers.. Journal of pharmaceutical and biomedical analysis Sep 2020. doi: 10.1016/j.jpba.2020.113639 [Pubmed: 33017796]
Resources:
Serum_samples https://www.precisionbiospecimens.com/]
33017796_paper_link https://www.sciencedirect.com/science/article/pii/S0731708520315259?via%3Dihub#tbl0020]
Assays:None
Clinical Assessments:None
SDY1693: The association between vaginal bacterial composition and miscarriage
Status: New
Description: To characterise vaginal bacterial composition in early pregnancy and investigate its relationship with first and second trimester miscarriages, the study conducted prospective profiling on 161 pregnancies by using 16S rRNA gene?based metataxonomics from 5 weeks? gestation in pregnancies ending in miscarriage (78) or uncomplicated term deliveries (83) matched for age, gestation and body mass index. Relative vaginal bacteria abundance, diversity and richness were measured and compared among cohorts. RESULTs: Vaginal bacterial composition in first trimester miscarriage is associated with reduced Lactobacillus spp. abundance and is independent of vaginal bleeding. Incomplete/complete miscarriage associated with higher proportions of Lactobacillus spp.?depleted communities compared with missed miscarriage. Early pregnancy vaginal bacterial stability was similar between miscarriage and term pregnancies.
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M3JL1IWXGZ
Subjects: 0
Study PI, contact:
NameOrganizationSite
David MacIntyre Imperial College London Division of the Institute of Reproduction and Developmental Biology
Publications:
The association between vaginal bacterial composition and miscarriage: a nested case-control study.. BJOG : an international journal of obstetrics and gynaecology Jan 2020. doi: 10.1111/1471-0528.15972 [Pubmed: 31573753]
Resources:
PRJEB32479 https://www.ebi.ac.uk/ena/browser/view/PRJEB32479]
paper_link https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/1471-0528.15972]
Silva bacterial database http://www.arb-silva.de]
Clustering tool: CLUSTVIS https://biit.cs.ut.ee/clustvis/]
Assays:None
Clinical Assessments:None
SDY1697: Influenza / S. aureus Superinfection
Status: New
Description: Infection of mice with Influenza virus, S. aureus, or both
Program/Contract:
ProgramContract
Systems Approach to Immunity and Inflammation RFA-AI-16-050 Systems Approach To Immunity And Inflammation
DOI: 10.21430/M3AVN5HGTN
Subjects: 14
Study PI, contact:
NameOrganizationSite
Vincent Tam Temple University Seattle Children's Research Institute
Publications:
PPARa exacerbates necroptosis, leading to increased mortality in postinfluenza bacterial superinfection.. Proceedings of the National Academy of Sciences of the United States of America Jul 2020. doi: 10.1073/pnas.2006343117 [Pubmed: 32581129]
Resources:
Assays:
Assay TypeNumber of Exp. Samples
DNA microarray 14
Clinical Assessments:None
SDY1699: Vaginal dysbiosis increases risk of PPROM, neonatal sepsis and is exacerbated by erythromycin
Status: New
Description: To understand the dynamics of vaginal microbiota compositions associated with PPROM and the impact by antibiotics, the study prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. RESULTS: vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases and persisted following membrane rupture. Vaginal dysbiosis was exacerbated by erythromycin treatment particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M31ZXG1MZW
Subjects: 119
Study PI, contact:
NameOrganizationSite
David MacIntyre Imperial College London Division of the Institute of Reproduction and Developmental Biology
Publications:
Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin.. BMC medicine Jan 2018. doi: 10.1186/s12916-017-0999-x [Pubmed: 29361936]
Resources:
PRJEB21325 https://www.ebi.ac.uk/ena/data/view/PRJEB21325]
ENA seq reads https://www.ebi.ac.uk/ena/browser/view/PRJEB21325]
Figshare https://figshare.com/articles/journal_contribution/Additional_file_1_Figure_S1_of_Vaginal_dysbiosis_increases_risk_of_preterm_fetal_membrane_rupture_neonatal_sepsis_and_is_exacerbated_by_erythromycin/5817027]
Assays:None
Clinical Assessments:None
SDY1701: Unique transcriptomic landscapes identified in isPTB and infectiion-PTB/AHC
Status: New
Description: The study compared placental villous transcriptomes from carefully phenotyped cohorts of PTB due to infection or isPTB (idiopathic spontaneous preterm birth) between 28?36 weeks gestation and healthy term placentas. Transcriptomic analyses revealed a unique expression signature for isPTB, which included three upregulated IGF binding proteins (IGFBP1, IGFBP2, and IGFBP6), supporting a role for aberrant IGF signaling in isPTB, and secondary signatures of inflammatory markers including TNC, C3, CFH, and C1R, which have been associated with placental maturity. In contrast, the expression signature of the PTB-infection cohort included upregulation of proliferative genes along with cell cycling and mitosis pathways. Together, these data suggest an isPTB molecular signature of placental hypermaturity, likely contributing to the premature activation of inflammatory pathways associated with birth and providing a molecular basis for idiopathic spontaneous birth
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M3CWCOQDNW
Subjects: 0
Study PI, contact:
NameOrganizationSite
Heather Brockway University of Cincinnati College of Medicine Department of Pediatrics
Publications:
Unique transcriptomic landscapes identified in idiopathic spontaneous and infection related preterm births compared to normal term births.. PloS one Nov 2019. doi: 10.1371/journal.pone.0225062 [Pubmed: 31703110]
Resources:
GSE118442 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE118442]
GSE73714 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE73714]
paper_link https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225062]
Assays:None
Clinical Assessments:None
SDY1466: Monozygotic and Dizygotic Twin Pair T-Cell Responses to Influenza Vaccination SLVP018 2013
Status: Updated
Description: Evaluate the variation in immune response between individuals and assess whether it changes as a function of age and similarity in genetic and environmental background (by comparing differences between monozygotic and dizygotic twin pairs of different ages).
Program/Contract:
ProgramContract
Human Immunology Project Consortium (HIPC) RFA-AI-14-007, RFA-AI-09-040 Vaccination and infection: indicators of immunological health and responsiveness
DOI: 10.21430/M33B64BQUE
Subjects: 21
Study PI, contact:
NameOrganizationSite
Mark Davis Stanford University Stanford University
Publications:
Variation in the human immune system is largely driven by non-heritable influences.. Cell Jan 2015. doi: 10.1016/j.cell.2014.12.020 [Pubmed: 25594173]
The FluPRINT dataset, a multidimensional analysis of the influenza vaccine imprint on the immune system.. Scientific data Oct 2019. doi: 10.1038/s41597-019-0213-4 [Pubmed: 31636302]
Resources:
CliicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01987349]
Assays:
Assay TypeNumber of Exp. Samples
CyTOF 8
Hemagglutination Inhibition 160
Clinical Assessments:None
SDY1471: B-cell Immunity to Influenza (SLVP017) 2013
Status: Updated
Description: Systems biology approach to examine effects of seasonal flu vaccination in adults of different ages on gene expression, cytokine stimulation and serum cytokines with parameters such as immune senescence to uncover new markers and mechanisms behind failure of immune function in many older people.
Program/Contract:
ProgramContract
Human Immunology Project Consortium (HIPC) RFA-AI-14-007, RFA-AI-09-040 Vaccination and infection: indicators of immunological health and responsiveness
DOI: 10.21430/M3WEPI1HA3
Subjects: 9
Study PI, contact:
NameOrganizationSite
Mark Davis Stanford University Stanford University
Publications:
The FluPRINT dataset, a multidimensional analysis of the influenza vaccine imprint on the immune system.. Scientific data Oct 2019. doi: 10.1038/s41597-019-0213-4 [Pubmed: 31636302]
Resources:
CliicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03020537]
Assays:
Assay TypeNumber of Exp. Samples
CyTOF 9
Hemagglutination Inhibition 56
Clinical Assessments:None
SDY1514: An Observational Study of Childhood Food Allergy (CoFAR2)
Status: Updated
Description: This observational study will investigate the developmental immunology of peanut, egg, and milk allergy in a cohort of milk- or egg-allergic children who are at risk for peanut allergy. This strategy will help to delineate, compare, and contrast biological markers and immunologic changes associated with the development of peanut allergy and loss of egg and milk allergy, while simultaneously evaluating important clinical and environmental influences likely to account for the recent rise in the prevalence of these allergies. The hallmark of food-allergic disease is the production of food-specific Immunoglobulin E (IgE) antibodies that represent an end result of a T helper 2 (Th2) influenced immune response. Currently, there is only a limited understanding of the mechanisms involved in the developmental course of food allergies. To effectively prevent or reverse the progression of food allergy, immune interventions will be needed. Furthermore, it is likely that successful strategies will need to be directed to those persons at identifiable risk (e.g., who have biomarkers associated with development of peanut allergy).
Program/Contract:
ProgramContract
Consortium for Food Allergy Research (CoFAR) RFA-AI-14-003,RFA-AI-09-039,RFA-AI-04-034 Immunobiology of Food Allergy and Its Treatment (CoFAR)
DOI: 10.21430/M3CCG5XNFF
Subjects: 515
Study PI, contact:
NameOrganizationSite
Scott Sicherer Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai
Publications:
Immunologic features of infants with milk or egg allergy enrolled in an observational study (Consortium of Food Allergy Research) of food allergy.. The Journal of allergy and clinical immunology May 2010. doi: 10.1016/j.jaci.2010.02.038 [Pubmed: 20451041]
The natural history of egg allergy in an observational cohort.. The Journal of allergy and clinical immunology Feb 2014. doi: 10.1016/j.jaci.2013.12.1041 [Pubmed: 24636473]
Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy.. The Journal of allergy and clinical immunology Jan 2015. doi: 10.1016/j.jaci.2014.10.007 [Pubmed: 25457149]
Resources:
ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT00356174]
Assays:None
Clinical Assessments:None
SDY1626: Transcriptome and Regulatory Maps of Decidua-derived Stromal Cells Inform Gene Discovery in Preterm Birth
Status: Updated
Description: While a genetic component of preterm birth (PTB) has long been recognized and recently mapped by genome-wide association studies (GWAS), the molecular determinants underlying PTB remain elusive. This stems in part from an incomplete availability of comprehensive functional genomic annotations in human cell types relevant to pregnancy and PTB. Here, we generated extensive transcriptional and chromatin annotations of cultured primary decidua-derived mesenchymal stromal/stem cells (MSCs) and in vitro differentiated decidual stromal cells (DSCs) and developed a computational framework to integrate these functional annotations with results from a GWAS of gestational duration in 56,384 women. This resulted in a significant enrichment of heritability estimates in functional noncoding regions in stromal cells, as well as in the discovery of additional loci associated with gestational duration and target genes of associated loci.
Program/Contract:
ProgramContract
March of Dimes March of Dimes
DOI: 10.21430/M3FQ76H3IG
Subjects: 4
Study PI, contact:
NameOrganizationSite
Marcelo Nobrega University of Chicago Department of Human Genetics
Publications:
Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth.. Science advances Dec 2020. doi: 10.1126/sciadv.abc8696 [Pubmed: 33268355]
Resources:
GEO Reference_PGR https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94038]
GEO Reference_NR2F2 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52008]
GEO Reference_FOSL2 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94038]
GEO Reference_FOXO1 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94037]
GEO Reference_input-NR2F2 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52008]
GEO Reference_input-FOXO1+PolII+PGR+FOSL2 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94038]
GEO Reference_GATA2 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108409]
GEO Reference_input-GATA2 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108409]
Price Lab website https://data.broadinstitute.org/alkesgroup/LDSCORE/]
Source code for the GWAS enrichment analyses https://github.com/CreRecombinase/ptb_workflowr]
H3K27ac_H3K4me1_and H4K4me3 histone modification peak coordinates https://egg2.wustl.edu/roadmap/data/byFileType/peaks/consolidated/narrowPeak/ucsc_compatible/]
Biorxiv https://www.biorxiv.org/content/10.1101/2020.04.06.017079v2]
paper_link https://advances.sciencemag.org/content/6/49/eabc8696.full]
Assays:
Assay TypeNumber of Exp. Samples
Other 1
RNA sequencing 18
Sequencing 72
Clinical Assessments:None
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