A5040835776- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Gene expression and cancer classification
- Chronic Lymphocytic Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Machine Learning in Bioinformatics
- Protein Degradation and Inhibitors
- Bioinformatics and Genomic Networks
- Psoriasis: Treatment and Pathogenesis
- Rheumatoid Arthritis Research and Therapies
- Sphingolipid Metabolism and Signaling
- Systemic Lupus Erythematosus Research
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Genetic Associations and Epidemiology
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Ovarian cancer diagnosis and treatment
- Spondyloarthritis Studies and Treatments
- thermodynamics and calorimetric analyses
- Multiple Myeloma Research and Treatments
- Pharmacological Effects of Natural Compounds
- Monoclonal and Polyclonal Antibodies Research
- Fractal and DNA sequence analysis
Predictive Science (United States)
2019-2024
Bristol-Myers Squibb (United States)
2022-2024
Bristol-Myers Squibb (Switzerland)
2019
University of Pittsburgh
2012-2014
Ozanimod (RPC1063) is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) 5 (S1PR5), which has shown therapeutic benefit in clinical trials relapsing multiple sclerosis ulcerative colitis. its active metabolite, RP-101075, exhibit similar specificity profile at S1P family vitro pharmacodynamic vivo. The NZBWF1 mouse model was used dosing mode to assess potential ozanimod RP-101075 an established animal systemic lupus erythematosus. Compared with...
Abstract Multiple myeloma (MM) is a plasma cell malignancy characterised by aberrant production of immunoglobulins requiring survival mechanisms to adapt proteotoxic stress. We here show that glutamyl-prolyl-tRNA synthetase (GluProRS) inhibition constitutes novel therapeutic target. Genomic data suggest GluProRS promotes disease progression and associated with poor prognosis, while downregulation in MM cells triggers apoptosis. developed NCP26, ATP-competitive ProRS inhibitor demonstrates...
Abstract Recent genetic and molecular classification of DLBCL has advanced our knowledge disease biology, yet were not designed to predict early events guide anticipatory selection novel therapies. To address this unmet need, we used an integrative multiomic approach identify a signature at diagnosis that will high risk clinical failure. Tumor biopsies from 444 newly diagnosed analyzed by WES RNAseq. A combination weighted gene correlation network analysis differential expression was...
Identification of genetic variants that are associated with disease is an important goal in elucidating the causes diseases. The patterns common diseases complex and may involve multiple interacting variants. Relief family algorithms a powerful tool for efficiently identifying disease, even if have nonlinear interactions without significant main effects. Many variations been developed over past two decades several them applied to single nucleotide polymorphism (SNP) data.We new spatially...
Ranking and identifying biomarkers that are associated with disease from genome-wide measurements holds significant promise for understanding the genetic basis of common diseases. The large number single nucleotide polymorphisms (SNPs) in studies (GWAS), however, makes this task computationally challenging when ranking is to be done a multivariate fashion. This paper evaluates performance graph-based method called label propagation (LP) efficiently ranks SNPs data. LP was evaluated on...
Abstract Finding biomarkers that provide shared link between disease severity, drug-induced pharmacodynamic effects and response status in human trials can number of values for patient benefits: elucidating current therapeutic mechanism-of-action, and, back-translating to fast-track development next-generation therapeutics. Both opportunities are predicated on proactive generation molecular profiles capture longitudinal trajectories before after pharmacological intervention. Here, we present...
Immunochemotherapy has been the mainstay of treatment for newly diagnosed diffuse large B-cell lymphoma (ndDLBCL) yet is inadequate many patients. In this work, we perform unsupervised clustering on transcriptomic features from a cohort ndDLBCL patients and identify seven clusters, one called A7 with poor prognosis, develop classifier to these clusters in independent cohorts. This high-risk cluster enriched activated cell-of-origin, low immune infiltration, high MYC expression, copy number...
ABSTRACT Diffuse large B‐cell lymphoma (DLBCL) patients that fail to achieve a complete metabolic response with frontline immunochemotherapy have poor prognosis. Genomic profiling has led broader understanding of the molecular drivers in DLBCL, but it is unknown how well current classifiers identify will experience primary treatment resistance (PTR). Using whole exome and RNA sequencing data from newly diagnosed DLBCL patients, we evaluated genomic landscape PTR compared non‐PTR DLBCL. We...
ABSTRACT Finding biomarkers that provide shared link between disease severity, drug-induced pharmacodynamic effects and response status in human trials can number of values for patient benefits: elucidating current therapeutic mechanism-of-action, and, back-translating to fast-track development next-generation therapeutics. Both opportunities are predicated on proactive generation molecular profiles capture longitudinal trajectories before after pharmacological intervention. Here, we present...
<h3>Background and aims</h3> Ozanimod (RPC1063) is a specific potent small molecule modulator of S1P<sub>1</sub>,<sub>5R</sub> that has shown therapeutic benefit in clinical trials relapsing multiple sclerosis ulcerative colitis. Its metabolite, RP-101075, shares ozanimod's specificity profile at the S1P receptor family <i>in vitro</i>, its pharmacokinetic (PK) pharmacodynamic vivo</i>. <h3>Methods</h3> The (NZB×NZW)F1 model was used dosing mode to assess an S1P<sub>1,5R</sub> systemic lupus...