A5060853762- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Single-cell and spatial transcriptomics
- Cancer Immunotherapy and Biomarkers
- Genetic factors in colorectal cancer
- Immune cells in cancer
- Lung Cancer Treatments and Mutations
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Adipose Tissue and Metabolism
- Ethics in Clinical Research
- Bioinformatics and Genomic Networks
- BRCA gene mutations in cancer
- Cancer, Hypoxia, and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Radiomics and Machine Learning in Medical Imaging
- Neurogenetic and Muscular Disorders Research
- Global Cancer Incidence and Screening
- Amyotrophic Lateral Sclerosis Research
- Cancer Treatment and Pharmacology
- Cancer Cells and Metastasis
- CAR-T cell therapy research
City Of Hope National Medical Center
2020-2025
Buck Institute for Research on Aging
2024-2025
Intermountain Healthcare
2020-2025
Merck & Co., Inc., Rahway, NJ, USA (United States)
2025
ProNAi Therapeutics (United States)
2024
Institute for Systems Biology
2023
University of Utah
2012-2022
State Street (United States)
2022
City of Hope
2021
Medical University of South Carolina
2017
Significance The evolution of peripheral immune cell abundance and signaling over time, as well how these cells interact with the tumor, may impact a cancer patient’s response to therapy. By developing an ecological population model, we provide evidence dynamic predator–prey-like relationship between circulating tumor size in patients that respond immunotherapy. This is not found either are nonresponsive immunotherapy or during chemotherapy. Single-cell RNA sequencing serial blood samples...
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder with progressive degeneration of cerebellar Purkinje cells (PCs) and other neurons caused by expansion a glutamine (Q) tract in the ATXN2 protein. We generated BAC transgenic lines which full-length human gene was transcribed using its endogenous regulatory machinery. Mice transgene expanded CAG repeat (BAC-Q72) developed cellular motor phenotype, whereas mice expressing wild-type (BAC-Q22) were indistinguishable from...
Introduction A digital twin is a virtual representation of patient's disease, facilitating real-time monitoring, analysis, and simulation. This enables the prediction disease progression, optimization care delivery, improvement outcomes. Methods Here, we introduce framework for type 2 diabetes (T2D) that integrates machine learning with multiomic data, knowledge graphs, mechanistic models. By analyzing substantial clinical dataset, constructed predictive models to forecast progression....
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the ATXN2 gene. The resides encoded region of gene resulting polyglutamine (polyQ) which has been assumed to result gain function, predominantly, for protein. We evaluated temporal cerebellar expression profiles RNA sequencing ATXN2Q127 mice versus wild-type (WT) littermates. are characterized a progressive motor phenotype onset, and have molecular neurophysiological...
Abstract The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells following chemotherapy is only partially understood. To understand the selection factors driving heterogeneity before and through adaptation to treatment, we profile single-cell RNA-sequencing (scRNA-seq) transcriptomes HGSOC tumors collected longitudinally during therapy. We analyze scRNA-seq data from two independent patient cohorts reveal that driven by three archetypal phenotypes, defined as oncogenic...
Over a century ago, Virchow proposed that cancer represents chronically inflamed, poorly healing wound. Normal wound is represented by transitory phase of inflammation, followed pro-resolution phase, with prostaglandin (PGE2/PGD2)-induced 'lipid class switching' producing inflammation-quenching lipoxins (LXA4, LXB4).
Spinocerebellar ataxia type 2 (SCA2) is a progressive autosomal dominant disorder caused by the expansion of CAG tract in ATXN2 gene. The SCA2 disease phenotype characterized cerebellar atrophy, gait ataxia, and slow saccades. mutation causes gains toxic normal functions gene product, ataxin-2, abnormally Purkinje cell firing frequency. Previously we investigated features controlling expression noted differences for constructs with varying lengths, suggestive repeat associated non-AUG...
Aging manifests as progressive deteriorations in homeostasis, requiring systems-level perspectives to investigate the gradual molecular dysregulation of underlying biological processes. Here, we report systemic changes regulation processes under multiple lifespan-extending interventions. Differential Rank Conservation (DIRAC) analyses mouse liver proteomics and transcriptomics data show that mechanistically distinct interventions (acarbose, 17α-estradiol, rapamycin, calorie restriction)...
Abstract The spinocerebellar ataxia type 2 (SCA2) gene ATXN2 has a prominent role in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS). In addition to cerebellar ataxia, motor neuron disease is often seen SCA2, CAG repeat expansions long normal range increase ALS risk. Also, lowering expression TDP-43 mice prolongs their survival. Here we investigated relationship with dysfunction vivo by comparing spinal cord (SC) transcriptomes reported from SOD1 patients those SCA2...
Accumulating evidence has suggested that cancer progression and therapeutic response depend on both tumor epithelium (EPI) microenvironment (TME). However, the dependency of clinical outcomes EPI vs. TME neither been clearly defined nor quantified. We classified 2373 colorectal (CRC) tumors into consensus molecular subtypes (CMS1-4) generated 10-gene TMES EPIS signatures as serendipitous derivatives most (positively negatively) correlated genes a highly-prognostic, ~ 500-gene signature we...
Abstract We conducted a spatial analysis of stage III colorectal adenocarcinomas using Hyperion Imaging Mass Cytometry, examining 52 tumors to assess the tumor microenvironment at single-cell level. This approach identified 10 distinct cell phenotypes in microenvironment, including stromal and immune cells, with subset showing proliferative phenotype. By focusing on neighborhood interactions tissue niches, particularly regions tumor-infiltrating lymphocytes, we investigated how cellular...
Abstract Recently, we serendipitously identified a pair of distinct 10-gene signatures, one associated with epithelial cells (EPIS) and the tumor microenvironment(TMES). When classified 2373 colorectal cancer (CRC) tumors into consensus molecular subtypes (CMS1-4), EPIS signature score was predominantly related to TME-poor CMS2/CMS3 classes highly predictive EGFRi outcomes in two clinical trial datasets large, real-world clinico-genomics dataset. By contrast, TMES strongly immune/stromal...
Abstract Colorectal cancer (CRC) is a leading cause of cancer-related deaths. An important contributor to CRC development, maintenance and metastasis the tumor microenvironment (TME). This cellular milieu contains neighboring epithelial cells, normal epithelium, fibroblasts, endothelial immune cells many others. The characterization TME critical for understanding biology as well determining specific features with clinical implications. Representing subset TME, (TIME) has characteristics that...
End stage breast cancer often presents with oligometastatic tumors and lacks effective treatment options. Previous studies leveraged post-mortem tissue procurement (also called rapid autopsy) programs to collect shortly after death for profiling by bulk whole exome sequencing (WES). This has revealed substantial heterogeneity in the genomes of metastatic estrogen receptor-positive (ER+) triple-negative cancers. In order understand both genotypes, transcriptional phenotypes, evolution these...
Apolipoprotein E (APOE) modifies human aging; specifically, the ε2 and ε4 alleles are among strongest genetic predictors of longevity Alzheimer's disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. In present study, we analyzed multi-omic association patterns across APOE genotypes, sex, biological age (BA) axes in 2,229 community dwelling individuals. Our analysis, supported by validation an independent cohort, identified diacylglycerols...
Lyme disease (LD) is growing in incidence, with nearly 500,000 cases diagnosed annually the United States. Despite treatment, some patients experience persistent symptoms. The immune mechanisms underlying LD remain poorly understood. We conducted a multiomic longitudinal analysis of 49 and matched controls, integrating plasma proteomics, metabolomics, PBMC immunophenotyping, meta-analysis skin lesions. identified compartmentalized responses acute LD, coordinated alterations circulating...
Abstract We previously identified a signature of 16 serum proteins that highlighted role the e2 allele APOE in lipid regulation via apolipoprotein B (APOB) and E (APOE), inflammation. The were profiled using aptamer-based Somalogic technology. Here, we validate expand protein combination mass-spectrometry, ELISA, Luminex, antibody-based Olink proteomics, blood transcriptomics. replicate association between APOB APOE, correct pattern genotypes level detect new associations complex...
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder caused by the expansion of a CAG tract in ATXN2 gene. The SCA2 phenotype characterized cerebellar ataxia, neuropathy and slow saccades. foreshortens life span currently without symptomatic or disease-modifying treatments. Identifying function-specific therapeutics for problematic due to limited knowledge function. As likely gain-of-toxic gain-of-normal function like other polyglutamine disorders, targeting expression may...
CDK4/6 inhibitors such as ribociclib are becoming widely used targeted therapies in hormone-receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer. However, cancers can advance due to drug resistance, a problem which tumor heterogeneity and evolution key features.Ribociclib-resistant HR+/HER2- CAMA-1 cancer cells were generated through long-term treatment. Characterization of sensitive resistant performed using RNA sequencing whole exome sequencing....
Abstract Single-cell RNA sequencing (scRNA-Seq) is an emerging strategy for characterizing immune cell populations. Compared to flow or mass cytometry, scRNA-Seq could potentially identify types and activation states that lack precise surface markers. However, currently limited due the need manually classify each from its transcriptional profile. While recently developed algorithms accurately annotate coarse (e.g. T cells versus macrophages), making fine distinctions CD8+ effector memory...
CAG repeat expansions in the ATXN2 (ataxin-2) gene can cause autosomal dominant disorder spinocerebellar ataxia type 2 (SCA2) as well increase risk of ALS. Abnormal molecular, motor, and neurophysiological phenotypes SCA2 mouse models are normalized by lowering transcription, reduction nonmutant Atxn2 expression has been shown to life span mice overexpressing TDP-43 (transactive response DNA-binding protein 43 kDa) ALS protein, demonstrating potential benefits targeting transcription humans....
Recently, it was suggested that consensus molecular subtyping (CMS) may aide in predicting response to EGFR inhibitor (cetuximab) therapies. We recently identified APC and TP53 as two tumor suppressor genes, when mutated, enhance cetuximab sensitivity represent easily measured biomarkers tumors or blood. Our study aimed use mutations (AP) refine the CMS classification better predict responses cetuximab. In total, 433 CRC were classified into CMS1-4 subtypes. The (CTX-S) signature scores of...
Over half of colorectal cancers (CRCs) are hard-wired to RAS/RAF/MEK/ERK pathway oncogenic signaling. However, the promise targeted therapeutic inhibitors, has been tempered by disappointing clinical activity, likely due complex resistance mechanisms that not well understood. This study aims investigate MEK inhibitor-associated signaling and identify subpopulation(s) CRC patients who may be sensitive biomarker-driven drug combination(s).We classified 2250 primary metastatic human tumors...
Apolipoprotein E (