A5000280486- PARP inhibition in cancer therapy
- Ovarian cancer diagnosis and treatment
- Cancer Genomics and Diagnostics
- Plant-Microbe Interactions and Immunity
- Legume Nitrogen Fixing Symbiosis
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Plant Pathogenic Bacteria Studies
- Advanced Breast Cancer Therapies
- Genomics and Phylogenetic Studies
- AI in cancer detection
- Radiomics and Machine Learning in Medical Imaging
- Gene expression and cancer classification
- Scientific Computing and Data Management
- Genetics, Bioinformatics, and Biomedical Research
- Pancreatic and Hepatic Oncology Research
- Advanced Biosensing Techniques and Applications
- Advanced Fluorescence Microscopy Techniques
- Explainable Artificial Intelligence (XAI)
- Ferroptosis and cancer prognosis
- DNA Repair Mechanisms
- Breast Cancer Treatment Studies
- Toxin Mechanisms and Immunotoxins
- Yeasts and Rust Fungi Studies
- Cancer Immunotherapy and Biomarkers
Oregon Health & Science University
2018-2025
OHSU Knight Cancer Institute
2019-2025
The University of Texas MD Anderson Cancer Center
2023
Oregon State University
2010-2020
ORCID
2018
Highly multiplexed tissue imaging makes detailed molecular analysis of single cells possible in a preserved spatial context. However, reproducible large multichannel images poses substantial computational challenge. Here, we describe modular and open-source pipeline, MCMICRO, for performing the sequential steps needed to transform whole-slide into single-cell data. We demonstrate use MCMICRO on tumor acquired using multiple platforms, thereby providing solid foundation continued development software.
Understanding how bacteria affect plant health is crucial for developing sustainable crop production systems. We coupled ecological sampling and genome sequencing to characterize the population genetic history of Rhodococcus distribution patterns virulence plasmids in isolates from nurseries. Analysis chromosome sequences shows that plants host multiple lineages Rhodococcus, suggested these are transmitted due independent introductions, reservoir populations, point source outbreaks....
Two diametric paradigms have been proposed to model the molecular co-evolution of microbial mutualists and their eukaryotic hosts. In one, mutualist host exhibit an antagonistic arms race each partner evolves rapidly maximize own fitness from interaction at potential expense other. opposing model, conflicts between are largely resolved is characterized by evolutionary stasis. We tested these frameworks in two lineages mutualistic rhizobia, Sinorhizobium fredii Bradyrhizobium japonicum. To...
The plant cytoskeleton underpins the function of a multitude cellular mechanisms, including those associated with developmental- and stress-associated signaling processes. In recent years, actin has been demonstrated to play key role in immune signaling, demonstration that pathogens target filaments block defense immunity. Herein, we quantified spatial changes host filament organization after infection Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), demonstrating type-III effector HopG1...
On the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with AKT inhibitor capivasertib and assess molecular markers response resistance.We performed safety lead-in followed by expansion in endometrial, triple-negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300 mg orally twice daily on 4-day 3-day off schedule was evaluated. Two levels (DL) were planned: 400 (DL1) 320 (DL-1)....
Mechanisms of therapeutic resistance and vulnerability evolve in metastatic cancers as tumor cells extrinsic microenvironmental influences change during treatment. To support the development methods for identifying these mechanisms individual people, here we present an omic multidimensional spatial (OMS) atlas generated from four serial biopsies with breast cancer 3.5 years therapy. This resource links detailed, longitudinal clinical metadata that includes treatment times doses, anatomic...
Members of Gram-positive Actinobacteria cause economically important diseases to plants. Within the Rhodococcus genus, some members can growth deformities and persist as pathogens on a wide range host The current model predicts that phytopathogenic isolates require cluster three loci present linear plasmid, with fas operon central virulence. Fas proteins synthesize, modify, activate mixture regulating cytokinins, which hormonal imbalance in plants, resulting abnormal growth. We sequenced...
Abstract The Cancer Genome Atlas (TCGA) and International Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) genome (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium, which aggregated data from 2,658 cancers across 38 tumour types, we compare WES WGS side-by-side 746 TCGA samples, finding that ~80% mutations overlap in covered exonic regions. We estimate low variant allele fraction (VAF <...
Abstract Background Pseudomonas fluorescens is a genetically and physiologically diverse species of bacteria present in many habitats association with plants. This produces large array secondary metabolites potential as natural products. P. isolate WH6 Germination-Arrest Factor (GAF), predicted small peptide or amino acid analog herbicidal activity that specifically inhibits germination seeds graminaceous species. Results We used hybrid next-generation sequencing approach to develop...
Molecular heterogeneity in metastatic breast cancer presents multiple clinical challenges accurately characterizing and treating the disease. Current diagnostic approaches offer limited ability to assess that exists among lesions throughout treatment course. We developed a precision oncology platform combines serial biopsies, multi-omic analysis, longitudinal patient monitoring, molecular tumor boards, with goal of improving management through enhanced understanding entire ecosystem within...
The accurate diagnosis of diseases caused by pathogenic bacteria requires a stable species classification. Rhodococcus fascians is the only documented member its ill-defined genus that capable causing disease on wide range agriculturally important plants. Comparisons genome sequences generated from isolates associated with diseased plants revealed level genetic diversity consistent them representing multiple species. To test this, we tree based more than 1700 homologous plant-associated...
The accurate identification and quantitation of RNA isoforms present in the cancer transcriptome is key for analyses ranging from inference impacts somatic variants to pathway analysis biomarker development subtype discovery. ICGC-TCGA DREAM Somatic Mutation Calling (SMC-RNA) challenge was a crowd-sourced effort benchmark methods isoform quantification fusion detection bulk sequencing (RNA-seq) data. It concluded 2018 with comparison 77 entries 65 on 51 synthetic tumors 32 cell lines...
Abstract Background: First-line CDKi and endocrine therapy has improved survival for patients with mHRBC. Upon progression, the optimal treatment strategy mHRBC without a targetable mutation in PIK3CA, AKT, PTEN or ESR1 is unclear. The CAPItello-291 trial showed that targeting PIK3CA pathway after progression-free survival, including identifiable genomic alterations AKT PTEN. Protein expression analysis may identify whether signaling pathways such as PIK3CA/AKT are upregulated proffer...
Abstract Multiplex tissue imaging enables single-cell spatial proteomics and transcriptomics but remains limited by incomplete molecular profiling, loss, probe failure. Here, we apply machine learning to impute protein abundance using multiplex data from a breast cancer cohort. We evaluate regularized linear regression, gradient-boosted trees, deep autoencoders, incorporating context enhance imputation accuracy. Our models achieve mean absolute errors between 0.05–0.3 on [0,1] scale, closely...
e13102 Background: First-line CDKi and endocrine therapy has improved survival for many patients (pts) with mHRBC. Yet, some pts still experience rapid disease progression within 6 months of initiation require a tailored therapeutic approach. To understand tumor microenvironment factors associated progression, we performed digital spatial protein profiling (DSP), RNA sequencing (RNAseq) multiplexed immunohistochemistry (mIHC) on samples collected from before after CDKi. Methods: We...
Rhodococcus is a genus of Gram-positive bacteria with species that can cause growth deformations to large number plant species. This ability disease hypothesized be dependent on cluster three gene loci an almost 200 kb-sized linear plasmid. To reevaluate the roles some genes in pathogenicity, we constructed and characterized deletion mutants fasR four fas genes. Findings confirmed fasR, which encodes putative transcriptional regulator, necessary for pathogenesis. However, genes, implicated...
In a pilot study, we evaluated the feasibility of real-time deep analysis serial tumor samples from triple negative breast cancer patients to identify mechanisms resistance and treatment opportunities as they emerge under therapeutic stress engendered by poly-ADP-ribose polymerase (PARP) inhibitors (PARPi). BRCA-mutant basal exceptional long-term survivor, striking destruction was accompanied marked infiltration immune cells containing CD8 effector cells, consistent with pre-clinical...
From a screen of 36 plant-associated strains Burkholderia spp., we identified 24 that suppressed leaf and pseudobulb necrosis orchid caused by B. gladioli. To gain insights into the mechanisms disease suppression, generated draft genome sequence from one suppressive strain, TC3.4.2R3. The is an estimated 7.67 megabases in size, with three replicons, two chromosomes, plasmid pC3. Using combination multilocus analysis phylogenomics, TC3.4.2R3 as seminalis, species within cepacia complex...