A5012832571- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- BRCA gene mutations in cancer
- Gut microbiota and health
- Genomics and Rare Diseases
- Lung Cancer Treatments and Mutations
- T-cell and B-cell Immunology
- Breast Cancer Treatment Studies
- vaccines and immunoinformatics approaches
- Transplantation: Methods and Outcomes
- Colorectal Cancer Treatments and Studies
- Immune cells in cancer
- Xenotransplantation and immune response
- Ferroptosis and cancer prognosis
- Genetic Mapping and Diversity in Plants and Animals
- Genetic Associations and Epidemiology
- Diabetes Management and Education
- Atherosclerosis and Cardiovascular Diseases
- Bladder and Urothelial Cancer Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Economic and Financial Impacts of Cancer
- Protein Degradation and Inhibitors
- SARS-CoV-2 detection and testing
- Bioinformatics and Genomic Networks
Providence Portland Medical Center
2020-2024
Providence Health & Services
2022-2024
Providence College
2020-2024
Cancer Research Center
2020-2022
St. Joseph Health System
2020
Abstract T cells recirculate through tissues and lymphatic organs to scan for their cognate antigen. Radiation therapy provides site-specific cytotoxicity kill cancer but also has the potential eliminate tumor-specific in field. To dynamically study effect of radiation on CD8 cell recirculation, we used Kaede mouse model photoconvert tumor-infiltrating monitor movement out field radiation. We demonstrate that results loss recirculation from tumor lymph node distant sites. Using scRNASeq, see...
Radiation therapy generates extensive cancer cell death capable of promoting tumor-specific immunity. Within the tumor, conventional dendritic cells (cDCs) are known to carry tumor-associated antigens draining lymph node (TdLN) where they initiate T-cell priming. How radiation influences cDC migration is poorly understood. Here, we show that immunological efficacy dependent on in radioimmunogenic tumors. Using photoconvertible mice, demonstrate impairs TdLN Comparative transcriptional...
e13048 Background: Treatment of metastatic (met) breast cancer (mBC) remains challenging due to tumor evolution, where tumors may acquire additional somatic alterations conferring resistance top treatment. We piloted a novel ctDNA assay, ProvSeq-Liquid (PS-L) in the longitudinal profiling mBC. PS-L is next generation sequencing assay that detects cfDNA variants 523 genes. determined reproducibility and applied cohort from newly diagnosed mBC patients compared paired primary met tissue...
Abstract Background Crohn’s diseases and ulcerative colitis, both of which are chronic immune-mediated disorders the gastrointestinal tract major contributors to overarching Inflammatory bowel diseases. It has become increasingly evident that pathological processes IBDs results from interactions between genetic environmental factors, can skew immune responses against normal intestinal flora. Methods The aim this study is assess analyze taxa diversity relative abundances in CD UC Saudi...
Radiation therapy induces immunogenic cell death in cancer cells, whereby released endogenous adjuvants are sensed by immune cells to direct adaptive responses. TLRs expressed on several subtypes recognize innate downstream inflammatory responses part via the adapter protein MyD88. We generated Myd88 conditional knockout mice interrogate its contribution response radiation distinct populations pancreatic cancer. Surprisingly, deletion Itgax (CD11c)-expressing dendritic had little discernable...
Abstract Purpose The progression of ductal carcinoma in situ (DCIS) to invasive breast (IBC) humans is highly variable. To better understand the relationship between them, we performed a multi-omic characterization co-occurring DCIS and IBC lesions cohort individuals. Methods Formalin-fixed paraffin-embedded tissue samples from 50 patients with were subjected DNA-seq whole transcriptome RNA-seq. Paired multi-omics profiles then interrogated for DNA mutations, gene expression pathway...
Large-scale gut microbiome sequencing has revealed key links between dysfunction and metabolic diseases such as type 2 diabetes (T2D). To date, these efforts have largely focused on Western populations, with few studies assessing T2D microbiota associations in Middle Eastern communities where prevalence is now over 20%. We analyzed the composition of stool 16S rRNA from 461 119 non-T2D participants Province Saudi Arabia. quantified abundance microbial to examine any significant differences...
Precision therapies and immunotherapies have revolutionized cancer care, with novel genomic biomarker-associated being introduced into clinical practice rapidly, resulting in notable gains patient survival. Despite this, there is significant variability the utilization of tumor molecular profiling that spans timing test ordering, comprehensiveness gene panels, decision support through therapy trial recommendations.
ABSTRACT Background Recent advances in xenotransplantation living and decedent humans using pig xenografts have laid promising groundwork towards future emergency use first human trials. Major obstacles remain though, including a lack of knowledge the genetic incompatibilities between donors recipients which may led to harmful immune responses against xenograft or dysregulation normal physiology. In 2022 two heart were transplanted into brain-dead decedents with minimized immunosuppression...
9546 Background: Viagenpumatucel-L (HS-110) is an allogeneic cellular vaccine derived from a human lung adenocarcinoma cell line transfected with gp96-Ig fusion protein. Gp96-Ig functions as antigen chaperone for dendritic activation and direct CD8+T expansion via cross presentation. DURGA multi-cohort study evaluating HS-110 plus anti-PD-1 mAbs in patients (pts) advanced NSCLC. We report on Cohort A, which enrolled previously-treated pts who had not received anti-PD(L)1 prior to entry....
Tumor mutational burden (TMB), a surrogate for tumor neoepitope burden, is used as pan-tumor biomarker to identify patients who may benefit from anti-program cell death 1 (PD1) immunotherapy, but it an imperfect biomarker. Multiple additional genomic characteristics are associated with anti-PD1 responses, the combined predictive value of these features and added informativeness each respective feature remains unknown. We evaluated whether machine learning (ML) approaches using proposed...
6622 Background: An ever-increasing number of biomarker-guided therapies, some with pan-cancer indications have expanded the oncologist’s toolbox for fighting advanced cancer. Despite this, not all cancer patients receive tumor genomic testing, or are tested a limited targets. Still others too late in their care journey to benefit from precision therapy. To assess impact removing testing barriers, we developed reflex protocol where comprehensive profiling (CGP) was routinely ordered by...
Abstract Background: Molecular profiling of ductal carcinoma in situ (DCIS) has shown some prognostic utility the clinic. However, there is still an incomplete understanding diversity molecular mechanisms by which DCIS progresses to invasive breast cancer (IBC).Here, we utilize integrative multi-omic co-occurring and IBC humans as a model for mapping relationship between tumor mutations, global gene expression morphological changes IBC. Methods: We performed targeted panel DNA sequencing...
e23109 Background: Immune checkpoint inhibitors (IO) have become a powerful precision therapy option to treat advanced stage cancer with biomarkers such as PD-L1, tumor mutational burden (TMB), and microsatellite instability (MSI) associated improved patient response rates. Despite this, many patients do not receive genomic testing for all IO biomarkers. Providence, large US community health system, developed pathologist-directed protocol where comprehensive profiling (CGP) was routinely...
<h3>Background</h3> The rapidly growing field of immunopeptidomics has greatly expanded our understanding the breadth targets that T cells can potentially recognize on cancer cells. Non-canonical peptides (NCP) derived from non-coding or untranslated regions genome, along with circRNA, aberrant splicing, transposable elements represent potential shared targetable alternative neoantigens, are not expressed in thymus. Recent data highlights some cryptic and appear to increase malignancy...
Abstract Precision therapies and immunotherapies have revolutionized cancer care, resulting in significant gains patient survival across tumor types. Despite this transformation there is variability the utilization of molecular profiling. To standardize testing, we designed a pathologist-directed test ordering system at time diagnosis utilizing 523-gene DNA/RNA hybrid comprehensive genomic profiling (CGP) panel. We assessed actionability rates, therapy choices, outcomes among 3,216 patients....
<title>Abstract</title> Population-scale genomics programs may enable increased access to genomic medicine. The Genomic Medicine for Everyone (Geno4ME) program was established across the diverse seven-state Providence Health system research and genome-guided care pathways patients’ lifetimes. Key components included targeted multi-lingual outreach underrepresented groups, a novel electronic informed consent (e-consent) education platform, whole genome sequencing (WGS) with clinical return of...
e15035 Background: Precision therapies and immunotherapies have revolutionized cancer care, with novel genomic biomarker-associated being introduced into clinical practice rapidly. We assessed the utility of comprehensive profiling (CGP)-based testing for identifying biomarkers associated approved therapies, in precision medicine basket trials (CT) across a large cohort advanced patients Providence health system. Methods: Advanced were tested utilizing CGP workflow between 2019-2021....
Abstract The balance of innate signaling through adaptor proteins such as MyD88 and TRIF is critical in directing the pattern inflammatory responses following exposure to endogenous adjuvants. While stimuli can cause inflammation that supports adaptive immunity, cancer myeloid cells be pre-polarized same signals suppress immune responses. We aim investigate regulating type I IFN secretion by tumors order improve secretion, activation cells, direct macrophage polarization CD8+ T cell mediated...