A5033124739- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Immune Cell Function and Interaction
- Computational Drug Discovery Methods
- Immune cells in cancer
- Gene Regulatory Network Analysis
- Immune responses and vaccinations
- Pulmonary Hypertension Research and Treatments
- Neonatal Respiratory Health Research
- Single-cell and spatial transcriptomics
- Chronic Myeloid Leukemia Treatments
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- T-cell and B-cell Immunology
- Tuberculosis Research and Epidemiology
- Genomics and Chromatin Dynamics
- CAR-T cell therapy research
- COVID-19 Clinical Research Studies
- Immunotherapy and Immune Responses
- Acute Lymphoblastic Leukemia research
- HIV Research and Treatment
- Mosquito-borne diseases and control
- Congenital Diaphragmatic Hernia Studies
- Complement system in diseases
- Chronic Lymphocytic Leukemia Research
Center for Discovery
2025
Hackensack University Medical Center
2014-2025
Hackensack Meridian Health
2019-2024
Stanford University
2016-2024
Institute of Infection and Immunity
2018-2023
Translational Research Informatics Center (Japan)
2023
Stanford Medicine
2016-2020
Wayne State University
2010-2019
Woodward (United States)
2013
University of Padua
2011
To find and validate generalizable sepsis subtypes using data-driven clustering.We used advanced informatics techniques to pool data from 14 bacterial transcriptomic datasets eight different countries (n = 700).Retrospective analysis.Persons admitted the hospital with sepsis.None.A unified clustering analysis across discovery revealed three subtypes, which, based on functional analysis, we termed "Inflammopathic, Adaptive, Coagulopathic." We then validated these in nine independent five...
Identifying the pathways that are significantly impacted in a given condition is crucial step understanding underlying biological phenomena. All approaches currently available for this purpose calculate P -value aims to quantify significance of involvement each pathway phenotype. These -values were previously thought be independent. Here we show not case, and many can considerably affect other's through “crosstalk” phenomenon. Although it intuitive various could influence other, presence...
Identification of novel therapeutic effects for existing US Food and Drug Administration (FDA)-approved drugs, drug repurposing, is an approach aimed to dramatically shorten the discovery process, which costly, slow risky. Several computational approaches use transcriptional data find potential repurposing candidates. The main hypothesis such that if gene expression signature a particular opposite disease, may have effect on disease. However, this not be optimal since it fails consider...
The transition from reversible to irreversible pulmonary arterial hypertension involves vascular senescence and can be countered by senolysis.
Rationale Premature infants exposed to oxygen are at risk for bronchopulmonary dysplasia (BPD), which is characterised by lung growth arrest. Inflammation important, but the mechanisms remain elusive. Here, we investigated inflammatory pathways and therapeutic targets in severe clinical experimental BPD. Methods results First, transcriptomic analysis with silico cellular deconvolution identified a lung-intrinsic M1-like-driven cytokine pattern newborn mice after hyperoxia. These findings...
Natural killer (NK) cells likely play an important role in immunity to malaria, but the effect of repeated malaria on NK cell responses remains unclear. Here, we comprehensively profiled response a cohort 264 Ugandan children. Repeated exposure was associated with expansion atypical, CD56 neg population that differed transcriptionally, epigenetically, and phenotypically from dim cells, including decreased expression PLZF Fc receptor γ-chain, increased histone methylation, protein LAG-3, KIR,...
Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the is associated with disease severity and between patients different outcomes. To test this, we integrated 4,780 blood transcriptome profiles aged 0 to 90 years infected one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, influenza, across 34 cohorts 18 countries, single-cell RNA sequencing 702,970 immune cells 289 samples three cohorts. Severe viral infection was increased...
Influx of eosinophils into the lungs is typically associated with type II responses during allergy and fungal parasitic infections. However, we previously reported that accumulate in lung lesions I inflammatory to Mycobacterium tuberculosis (Mtb) humans, macaques, mice, which they support host resistance. Here show migrate macaques mice as early one week after Mtb exposure. In this influx CCR3 independent instead requires cell-intrinsic expression oxysterol receptor GPR183, highly expressed...
Abstract Motivation Drug repurposing is a potential alternative to the classical drug discovery pipeline. Repurposing involves finding novel indications for already approved drugs. In this work, we present machine learning-based method repurposing. This explores anti-similarity between drugs and disease uncover new uses More specifically, our proposed takes into account three sources of information: (i) large-scale gene expression profiles corresponding human cell lines treated with small...
Drug screening for improved function and transcriptomics of iPSC-derived endothelial cells from patients with pulmonary hypertension reveals AG1296.
Each year 3-6 million people develop life-threatening severe dengue (SD). Clinical warning signs for SD manifest late in the disease course and are nonspecific, leading to missed cases excess hospital burden. Better prognostics urgently needed.We integrated 11 public datasets profiling blood transcriptome of 365 patients all ages from seven countries, encompassing biological, clinical, technical heterogeneity. We performed an iterative multi-cohort analysis identify differentially expressed...
Pulmonary arterial hypertension (PAH) is characterized by progressive narrowing of pulmonary arteries, resulting in right heart failure and death. BMPR2 (bone morphogenetic protein receptor type 2) mutations account for most familial PAH forms whereas reduced present many idiopathic forms, suggesting dysfunctional signaling to be a key feature PAH. Modulating therapeutically promising, yet how downregulated unclear.We intended identify pharmaceutically target modifier genes improve PAH.We...
Results from the SCOT (Scleroderma: Cyclophosphamide Or Transplantation) clinical trial demonstrated significant benefits of haematopoietic stem cell transplant (HSCT) versus cyclophosphamide (CTX) in patients with systemic sclerosis. The objective this study was to test hypothesis that transplantation stabilises autoantibody repertoire favourable outcomes.
Abstract Predicting the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for viral infections and validate it in independent data, including COVID-19. We developed logistic regression-based validated multiple infection settings used training data (N = 705) from 21 retrospective transcriptomic clinical studies influenza other illnesses looking at preselected panel host immune response messenger RNAs. selected 6 RNAs...
Background Polyclonal autologous T cells that are epigenetically reprogrammed through mTOR inhibition and IFN-α polarization (RAPA-201) represent a novel approach to the adoptive cell therapy of cancer. Ex vivo results causes shift towards central memory (T CM ) whereas ex promotes type I cytokines, with each these functions known enhance Rapamycin-resistant polarized for II cytokine phenotype were previously evaluated in allogeneic transplantation context. Methods The clinical trial (...
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common diagnosed aggressive lymphoma, with poor outcomes in those who experience relapsed or refractory (R/R) disease. Landmark clinical trials have demonstrated efficacy and safety of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for patients R/R DLBCL, though further exploration real-world (RWOs) data warranted. Methods: A retrospective chart review was performed to collect patient disease characteristics from DLBCL...
Donor lymphocyte infusions (DLIs) are an effective treatment for relapsed Chronic myeloid leukemia (CML) after allogeneic transplantation but limited by the occurrence of GVHD. CD8+ T lymphocytes involved in pathogenesis GVHD may not be essential graft-versus-leukemia (GVL) effect CML. We have treated 26 CML patients with posttransplantation relapse CD8-depleted DLI. Thirteen 15 (87%) who early-phase achieved complete cytogenetic response, only 1 11 advanced-phase disease response. Acute...
The accumulation of high-throughput data in public repositories creates a pressing need for integrative analysis multiple datasets from independent experiments. However, study heterogeneity, bias, outliers and the lack power available methods present real challenge integrating genomic data. One practical drawback many P-value-based meta-analysis methods, including Fisher's, Stouffer's, minP maxP, is that they are sensitive to outliers. Another that, because perform just one statistical test...