A5007096218- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- Immune Cell Function and Interaction
- Gene expression and cancer classification
- Estrogen and related hormone effects
- Gut microbiota and health
- Breast Cancer Treatment Studies
- MicroRNA in disease regulation
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Genetics and Neurodevelopmental Disorders
- Metabolism, Diabetes, and Cancer
- Inflammasome and immune disorders
- Bioinformatics and Genomic Networks
- HER2/EGFR in Cancer Research
- Peptidase Inhibition and Analysis
- Stress Responses and Cortisol
Dartmouth Cancer Center
2021-2024
Dartmouth College
2014-2024
Dartmouth–Hitchcock Medical Center
2018-2023
Hanover College
2023
Cotton (United States)
2022
Although it is established that fatty acid (FA) synthesis supports anabolic growth in cancer, the role of exogenous FA uptake remains elusive. Here we show that, during acquisition resistance to HER2 inhibition, metabolic rewiring breast cancer cells favors reliance on over de novo synthesis. Through cDNA microarray analysis, identify transporter CD36 as a critical gene upregulated with acquired inhibitor lapatinib. Accordingly, resistant exhibit increased and plasticity. Genetic or...
The epithelial-to-mesenchymal transition (EMT) is frequently co-opted by cancer cells to enhance migratory and invasive cell traits. It a key contributor heterogeneity, chemoresistance, metastasis in many carcinoma types, where the intermediate EMT state plays critical tumor-initiating role. We isolate multiple distinct single-cell clones from SUM149PT human breast line spanning spectrum having diverse migratory, tumor-initiating, metastatic qualities, including three unique intermediates....
Neuroinflammation is a well-characterized pathophysiology occurring in association with the progression of Parkinson's disease. Characterizing cellular and molecular basis neuroinflammation critical to understanding its impact on incidence PD other neurologic disorders. Inflammasomes are intracellular pro-inflammatory pattern-recognition receptors capable initiating propagating inflammation. These complexes well characterized innate immune system activity NLRP3 inflammasome has been reported...
Approximately 25% of breast cancers overexpress and depend on the receptor tyrosine kinase ERBB2, one 4 ERBB family members. Targeted therapies directed against ERBB2 have been developed used clinically, but many patients continue to develop resistance such therapies. Although much effort has focused elucidating mechanisms acquired ERBB2-targeted therapies, involvement ERBB4 remains elusive controversial. We demonstrate that genetic ablation ERBB4, not ERBB1-3, led apoptosis in...
Stratifying breast cancer into specific molecular or histologic subtypes aids in therapeutic decision-making and predicting outcomes; however, these may not be as distinct previously thought. Patients with luminal-like, estrogen receptor (ER)-expressing tumors have better prognosis than patients more aggressive, triple-negative basal-like tumors. There is, a subset of luminal-like that express lower levels ER, which exhibit features. We found expressing traditionally considered to represent...
Targeted therapies have improved outcomes for certain cancer subtypes, but cytotoxic chemotherapy remains a mainstay triple-negative breast (TNBC). The epithelial-to-mesenchymal transition (EMT) is developmental program co-opted by cells that promotes metastasis and chemoresistance. There are no therapeutic strategies specifically targeting mesenchymal-like cells. We report the US Food Drug Administration (FDA)-approved chemotherapeutic eribulin induces ZEB1-SWI/SNF-directed chromatin...
Objective The aryl hydrocarbon receptor (AHR) plays a key role in obesity. In vitro studies revealed that the tryptophan metabolite kynurenine (Kyn) activates AHR signaling cultured hepatocytes. objective of this study was to determine whether Kyn activated mice induce Methods Mice were fed low‐fat diet and same supplemented with Kyn. Body mass, liver status, expression identified relevant genes determined. Results caused gain significant body develop fatty hyperglycemia, increase levels...
While changes in DNA methylation are known to occur early breast carcinogenesis and the landscape of tumour is profoundly altered compared with normal tissue, there have been limited efforts identify field cancerization effects histologically tissue adjacent tumour. Matched tumour, ipsilateral (ipsilateral-normal), contralateral (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used select epithelial cells neoplastic for...
Abstract The Epithelial-to-Mesenchymal Transition (EMT) is a developmental cellular program frequently coopted by cancer cells 1 and key contributor to both heterogeneity in solid tumors 2–4 later stage chemo-resistance metastasis 5,6 . Rather than being switch from an epithelial mesenchymal state, increasing evidence points the existence of intermediate EMT states, wherein co-express traits 7–13 Multiple stable states possessing unique characteristics exist across spectrum 7,8,14,15 ,...
Abstract Recent advances in deep learning, particularly unsupervised approaches, have shown promise for furthering our biological knowledge through their application to gene expression datasets, though applications epigenomic data are lacking. Here, we employ an learning framework with variational autoencoders (VAEs) learn latent representations of the DNA methylation landscape from three independent breast tumor datasets. Through interrogation methylation-based learned dimension activation...
Polymorphisms in microRNAs and their target sites can disrupt microRNA-dependent gene regulation, have been associated with cancer susceptibility. However, genome-scale analyses of microRNA-related genetic variation are lacking. We tested the associations ~40 000 common [minor allele frequency (MAF) ≥5%], single nucleotide polymorphisms (miR-SNPs), risk head neck squamous cell carcinoma (HNSCC) a discovery population, validated selected loci an independent population among total 2198 cases...
Head and neck squamous cell carcinoma (HNSCC) is commonly diagnosed at an advanced stage, prognosis for such patients poor. There remains a gap in our understanding of genetic variants related with HNSCC prognosis. miRNA-related single nucleotide polymorphisms (miR-SNPs) are class gene-regulatory potential. We used genome-scale approach independent patient populations two-stage to test 40,286 common miR-SNPs association survival the discovery population (n = 847), selected strongest...
Despite recent evidence that 5-hydroxymethylcytosine (5hmC) possesses roles in gene regulation distinct from 5-methylcytosine (5mC), relatively little is known regarding the functions of 5hmC mammalian tissues. To address this issue, we utilized an approach combining both paired bisulfite (BS) and oxidative (oxBS) DNA treatment, to resolve genome-wide patterns 5mC normal breast tissue disease-free women. Although less abundant than 5mC, was differentially distributed, consistently enriched...
Members of the BTB-ZF transcription factor family regulate immune system. Our laboratory identified that member Zbtb20 contributes to differentiation, recall responses, and metabolism CD8 T cells. Here, we report a characterization transcriptional epigenetic signatures controlled by at single-cell resolution during effector memory phases cell response. Without Zbtb20, programs associated with formation were up-regulated throughout A signature open chromatin was genes controlling activation,...
Abstract This manuscript describes the development of a resource module that is part learning platform named ‘NIGMS Sandbox for Cloud-based Learning’, https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis described in editorial authored by National Institute General Medical Sciences: NIGMS Sandbox: A Learning Platform toward Democratizing Cloud Computing Biomedical Research at beginning this supplement. delivers materials introducing utility BASH (Bourne Again Shell) programming...
Background: Epithelial-to-mesenchymal transition (EMT) is an early step in the invasion-metastasis cascade, involving progression through intermediate cell states. Due to challenges with isolating states, genome-wide cytosine modifications that define are not completely understood. Methods: The authors measured multiple DNA modification marks and chromatin accessibility across clonal populations residing specific EMT Results: Clones exhibiting more phenotypes demonstrated increased...
Abstract The epithelial-mesenchymal transition (EMT) is a developmental program co-opted by tumor cells that aids the initiation of metastatic cascade. Tumor undergo EMT are relatively chemoresistant, and there currently no therapeutic avenues specifically targeting have acquired mesenchymal traits. We show treatment mesenchymal-like triple-negative breast cancer (TNBC) with microtubule-destabilizing chemotherapeutic eribulin, which FDA-approved for advanced cancer, leads to...
Abstract Resident memory (Trm) cells play an essential role in anti-tumor immunity. However, little is known about the precursors that differentiate into protective Trm populations against cancer. Here we employed established model of B16 melanoma neoadjuvant anti-CD4 therapy, to track tumor antigen-specific CD8+ T through tissues and across time; from their priming as effectors differentiation Trm. We show tumor-draining lymph nodes (TDLNs) contain Teff begin express canonical markers CD103...
Abstract 5-hydroxymethylcytosine (5hmC) is generated by oxidation of 5-methylcytosine (5mC), however little understood regarding the distribution and functions 5hmC in mammalian cells. We determined genome-wide 5mC normal breast tissue from disease-free women. Although less abundant than 5mC, differentially distributed, consistently enriched among breast-specific enhancers transcriptionally active chromatin. In contrast, regulatory regions associated with transcriptional inactivity were...
MYC is one of the most dysregulated oncogenes and thought to be fundamental tumor formation and/or maintenance in many cancer types. This dominant pro-tumor activity makes an attractive target for therapy. However, a transcription factor lacking enzymatic activity, structure its two domains unknown e.g., transactivation domain. Consequently, few direct MYC-targeting therapies have been developed, none successful clinic. Nevertheless, significant effort has devoted understanding mechanisms...
Abstract/summary Stratifying breast cancer into specific molecular or histological subtypes aids in therapeutic decision-making and predicting outcomes, however, these may not be as distinct previously thought. Patients with luminal-like, Estrogen Receptor (ER)- expressing tumors have better prognosis than patients more aggressive, triple- negative basal-like tumors. There is, a subset of luminal-like that express lower levels ER, which exhibit features. We found traditionally considered to...