A5059515000- Cancer, Lipids, and Metabolism
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Mathematical Biology Tumor Growth
- COVID-19 Clinical Research Studies
- Gene expression and cancer classification
- Peroxisome Proliferator-Activated Receptors
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- Bioinformatics and Genomic Networks
- SARS-CoV-2 and COVID-19 Research
- Metabolomics and Mass Spectrometry Studies
- Influenza Virus Research Studies
- Long-Term Effects of COVID-19
- Bacterial Infections and Vaccines
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Tannin, Tannase and Anticancer Activities
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- COVID-19 and Mental Health
- Adipokines, Inflammation, and Metabolic Diseases
- Diabetes and associated disorders
- Liver physiology and pathology
Yale University
2022-2025
University of Florida
2024-2025
Institute For Defense Analyses
2024-2025
Center for Systems Biology
2024
University of New Haven
2023
UConn Health
2017-2020
University of California, Irvine
2012-2016
Applied Mathematics (United States)
2013
1alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3] regulates calcium homeostasis and controls cellular differentiation proliferation. The vitamin D receptor (VDR) is a ligand-regulated transcription factor that recognizes cognate response elements (VDREs) formed by direct or everted repeats of PuG(G/T)TCA motifs separated 3 6 bp (DR3 ER6). Here, we have identified 1,25(OH)2D3 target genes combining 35,000+ gene microarrays genome-wide screens for consensus DR3 ER6 elements, containing single...
The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1–3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling >15,000 longitudinal blood nasal samples 540 participants the using 14 distinct assays. These unbiased analyses identify cellular molecular signatures present within 72 h hospital admission that...
BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation molecular and cellular profiles the full course can link immune programs coordination progression heterogeneity.METHODSWe performed deep immunophenotyping conducted longitudinal multiomics modeling, integrating 10 assays 1,152 Immunophenotyping Assessment...
Abstract Summary With the increased reliance on multi-omics data for bulk and single cell analyses, availability of robust approaches to perform unsupervised learning clustering, visualization, feature selection is imperative. We introduce nipalsMCIA, an implementation multiple co-inertia analysis (MCIA) joint dimensionality reduction that solves objective function using extension Non-linear Iterative Partial Least Squares (NIPALS). applied nipalsMCIA both datasets observed significant...
Ferroptosis is a recently discovered form of iron-dependent regulated cell death (RCD) that occurs via peroxidation phospholipids containing polyunsaturated fatty acid (PUFA) moieties. Activating this an emerging strategy in cancer treatment. Because multiple pathways and molecular species contribute to the ferroptotic process, predicting which tumors will be sensitive ferroptosis challenge. We thus develop mathematical model several critical order perform systems-level analysis process....
Predictive biological signatures provide utility as biomarkers for disease diagnosis and prognosis, well prediction of responses to vaccination or therapy. These are identified from high-throughput profiling assays through a combination dimensionality reduction machine learning techniques. The genes, proteins, metabolites, other analytes that compose also generate hypotheses on the underlying mechanisms driving responses, thus improving understanding. Dimensionality is critical step in...
Abstract Mass cytometry, also known as CyTOF, is a newly developed technology for quantification and classification of immune cells that can allow analysis over three dozen protein markers per cell. The high dimensional data generated requires innovative methods visualization. We conducted comparative four dimension reduction techniques – principal component (PCA), isometric feature mapping (Isomap), t-distributed stochastic neighbor embedding (t-SNE), Diffusion Maps by implementing them on...
Systems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing differences in outcome. Comparing such is challenging due variability study designs. To address this, we established a community resource compare predicting B. pertussis booster generate experimental data for explicit purpose of model evaluation. We here describe our second prediction challenge using this resource, where benchmarked 49...
Abstract Combined agonist stimulation of the TNFR costimulatory receptors 4-1BB (CD137) and OX40(CD134) has been shown to generate supereffector CD8 T cells that clonally expand greater levels, survive longer, produce a quantity cytokines compared stimulated with an either receptor individually. In order understand mechanisms for this effect, we have created mathematical model activation cell intracellular signaling network by mono- or dual-costimulation. We show status is generated via...
Ovarian cancer (OC) has an overall modest number of mutations that facilitate a functional immune infiltrate able to recognize tumor mutated antigens, or neoantigens. Although patient-derived xenografts (PDXs) can partially model the mutational load and mimic response chemotherapy, no study profiled neoantigen-driven in OC PDXs. Here we demonstrate genomic status primary from patient be recapitulated vivo PDX model, with goal defining autologous T cells activation by neoantigens using...
Ovarian cancer (OVC) is the most lethal of gynecological malignancies, with diagnosis often occurring during advanced stages disease. Moreover, a majority cases become refractory to chemotherapeutic approaches. Therefore, it important improve our understanding molecular dependencies underlying disease identify novel diagnostic and precision therapeutics for OVC. Cancer cells are known sequester iron, which can potentiate progression through mechanisms that have not yet been completely...
Abstract Platelets are uniquely positioned as mediators of not only hemostasis but also innate immunity. However, how age and geriatric conditions such frailty influence platelet function during an immune response remains unclear. We assessed the transcriptome at baseline following influenza vaccination in Younger (age 21–35) Older ≥65) adults (including community‐dwelling individuals who were largely non‐frail skilled nursing facility (SNF)‐resident nearly all met criteria for frailty)....
Hospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles the full course can link immune programs coordination progression heterogeneity. In this study, we carried out deep immunophenotyping conducted longitudinal multi-omics modeling integrating ten distinct assays on a total 1,152 IMPACC participants identified several...
Systems vaccinology studies have identified factors affecting individual vaccine responses, but comparing these findings is challenging due to varying study designs. To address this lack of reproducibility, we established a community resource for Bordetella pertussis booster responses and host annual contests predicting patients' vaccination outcomes. We report here on our experiences with the "dry-run" prediction contest. found that, among 20+ models adopted from literature, most successful...
Abstract Motivation With the increased reliance on multi-omics data for bulk and single cell analyses, availability of robust approaches to perform unsupervised analysis clustering, visualization, feature selection is imperative. Joint dimensionality reduction methods can be applied datasets derive a global sample embedding analogous single-omic techniques such as Principal Components Analysis (PCA). Multiple co-inertia (MCIA) method joint that maximizes covariance between block-...
Abstract Computational models that predict an individual's response to a vaccine offer the potential for mechanistic insights and personalized vaccination strategies. These often stem from small cohort studies focusing on single vaccines limiting their generalizability. The ability assess performance of resulting would be improved by comparing independent datasets. We established prototype platform evaluates Models Immunity Pertussis Booster vaccinations (CMI-PB). It aims generate...
A large number of growth factors and drugs are known to act in a biphasic manner: at lower concentrations they cause increased division target cells, whereas higher the mitogenic effect is inhibited. Often, molecular details factor known, inhibitory not. Hepatoctyte Growth Factor, HGF, has recently been recognized as strong mitogen that present microenvironment solid tumors. Recent evidence suggests HGF acts manner on tumor growth. We build multi-species model action cells using different...
Abstract The goal of cancer immunotherapy is to boost a patient’s immune response tumor. Yet, the design an effective complicated by various factors, including potentially immunosuppressive tumor microenvironment, immune-modulating effects conventional treatments, and therapy-related toxicities. These complexities can be incorporated into mathematical computational models that then used aid in rational therapy design. In this review, we survey modeling approaches under umbrella major...