Kami Chiotti
A5036202114- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Evolution and Genetic Dynamics
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Fungal and yeast genetics research
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Plant and animal studies
- Single-cell and spatial transcriptomics
- Hepatitis B Virus Studies
- Molecular Biology Techniques and Applications
- Genomics and Rare Diseases
- Prostate Cancer Treatment and Research
- Bioinformatics and Genomic Networks
- Cancer Risks and Factors
- Xenotransplantation and immune response
- Mesenchymal stem cell research
- Estrogen and related hormone effects
- Bacterial biofilms and quorum sensing
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Yeasts and Rust Fungi Studies
Oregon Health & Science University
2013-2024
University of Montana
2011-2014
McLaughlin Research Institute
2000
The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling Multiple Cancers project, our effort to generate a comprehensive encyclopedia somatic mutation calls for TCGA enable robust cross-tumor-type analyses. Our approach accounts variance and batch effects introduced by rapid advancement DNA extraction,...
As organisms adaptively evolve to a new environment, selection results in the improvement of certain traits, bringing about an increase fitness. Trade-offs may result from this process if function other traits is reduced alternative environments either by adaptive mutations themselves or accumulation neutral elsewhere genome. Though cost adaptation has long been fundamental premise evolutionary biology, existence and molecular basis for trade-offs are not well-established. Here, we show that...
Somatic mutations in cancer are more frequent heterochromatic and late-replicating regions of the genome. We report that regional disparities mutation density virtually abolished within transcriptionally silent genomic cutaneous squamous cell carcinomas (cSCCs) arising an XPC−/− background. cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access DNA machinery chromatin-rich as primary cause for disparity. Strikingly, we find increasing levels...
Infiltration of T cells in breast tumors correlates with improved survival patients cancer, despite relatively few mutations these tumors. To determine if T-cell specificity can be harnessed to augment immunotherapies we sought identify the alpha-beta paired receptors (TCRs) tumor-infiltrating lymphocytes shared between multiple patients. Because TCRs function as heterodimeric proteins, used an emulsion-based RT-PCR assay link and amplify TCR pairs. Using this on engineered hybridomas,...
Women diagnosed with breast cancer within 5 years of childbirth have poorer prognosis than nulliparous or pregnant women. Weaning-induced involution is implicated, as the collagen-rich, immunosuppressive microenvironment involuting mammary gland tumor promotional in mice. To investigate role fibroblasts, isolated PDGFRα+ cells from and postweaning mice were assessed for activation phenotype protumorigenic function. Fibroblast during was evident by increased expression fibrillar collagens,...
Abstract Representative in vitro model systems that accurately response to therapy and allow the identification of new targets are important for improving our treatment prostate cancer. Here we describe molecular characterization drug testing a panel 20 cancer cell lines. The lines cluster into distinct subsets based on RNA expression, which is largely driven by functional Androgen Receptor (AR) expression. KLK3 , AR-responsive gene encodes specific antigen, shows greatest variability...
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 <...
BACKGROUNDHER2-targeting therapies have great efficacy in HER2-positive breast cancer, but resistance, part due to HER2 heterogeneity (HET), is a significant clinical challenge. We previously described that phase II neoadjuvant trastuzumab emtansine (T-DM1) and pertuzumab (P) trial early-stage none of the patients with HER2-HET tumors had pathologic complete response (pCR).METHODSTo investigate cellular molecular differences among according pCR, we performed RNA sequencing ERBB2 FISH 285...
Abstract Background Interspecific hybridization occurs in every eukaryotic kingdom. While hybrid progeny are frequently at a selective disadvantage, some instances their increased genome size and complexity may result greater stress resistance than ancestors, which can be adaptively advantageous the edges of ancestors' ranges. this phenomenon has been repeatedly documented field, response populations to long-term selection not often explored lab. To fill knowledge gap we crossed two most...
Abstract The BET bromodomain protein BRD4 is a chromatin reader that regulates transcription, including in cancer. In prostate cancer, specifically, the anti-tumor activity of inhibition has been principally linked to suppression androgen receptor (AR) function. MYC well-described target gene multiple cancer types, and prior work demonstrates plays an important role promoting cell survival. Importantly, several clinical trials are ongoing, However, there limited information about...
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 Evolutionary adaptation of Pseudomonas aeruginosa to the cystic fibrosis lung is limited by genetic variation, which depends on rates horizontal gene transfer and mutation supply. Because each may increase following secondary infection or mutator emergence, we sought ascertain incidence variability in populations containing lacking mutators. Forty-nine strains collected over 3 years from 16 patients were phenotyped for antibiotic resistance status genotyped repetitive-sequence PCR...
To build a catalog of peptides presented by breast cancer cells, we undertook systematic MHC class I immunoprecipitation followed elution I-loaded in cells. We determined the sequence 3196 ligands representing 1921 proteins from panel 20 cell lines. After removing duplicate peptides, i.e., same peptide eluted more than one line, total number unique was 2740. Of eluted, 1750 had been previously identified, and these, sixteen have shown to be immunogenic. Importantly, half these immunogenic...
RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) characterize the minority LUADs lacking apparent in pathway. We show that WGS analysis uncovers RPA(+) 28 (33%) samples. Among remaining 57 cases, observe focal deletions targeting promoter or transcription start site STK11 (n = 7) KEAP1 3), and mutations associated with...
Abstract Background Resistance to HER2-targeted therapeutics remains a significant clinical problem in HER2+ breast cancer patients with advanced disease. This may be particularly true for basal subtype disease, as recent evidence suggests they receive limited benefit from standard of care therapies. Identification drivers resistance and aggressive disease that can targeted clinically has the potential impact patient outcomes. Methods We performed siRNA knockdown screens genes differentially...
Metastasis is the most dreaded outcome after a breast cancer diagnosis, and little known regarding what triggers or promotes to spread distally, how prevent eradicate metastasis effectively. Bilateral cancers are an uncommon form of cancers. In our study, percentage bilateral were clonally related based on copy number variation profiling. Whole exome sequencing comparative sequence analysis revealed that limited somatic mutations acquired in this “breast-to-breast” might promote distant...
Abstract Subclonal reconstruction algorithms use bulk DNA sequencing data to quantify parameters of tumor evolution, allowing an assessment how cancers initiate, progress and respond selective pressures. We launched the ICGC–TCGA (International Cancer Genome Consortium–The Atlas) DREAM Somatic Mutation Calling Tumor Heterogeneity Evolution Challenge benchmark existing subclonal algorithms. This 7-year community effort used cloud computing 31 on 51 simulated tumors. Algorithms were scored...
Objective To evaluate the growth factor responses associated with myocardial angiogenesis. Design Mice were treated transmyocardial revascularization (TMR) and evaluated for angiogenic responses. Methods TMR was performed via thoractomy a 27 g needle. At 2, 5, 7 days post-treatment, hearts removed from control groups, then assayed angiogenesis, fibroblast (FGF)-2 expression vascular endothelial cell (VEGF) expression. Results caused an reaction in blood vessels at post-TMR treatment....
Abstract Tumours are dynamically evolving populations of cells. Subclonal reconstruction algorithms use bulk DNA sequencing data to quantify parameters tumour evolution, allowing assessment how cancers initiate, progress and respond selective pressures. A plethora subclonal have been created, but their relative performance across the varying biological technical features real-world cancer genomic is unclear. We therefore launched ICGC-TCGA DREAM Somatic Mutation Calling -- Tumour...