A5011384968- Estrogen and related hormone effects
- Cancer Immunotherapy and Biomarkers
- Computational Drug Discovery Methods
- RNA modifications and cancer
- Biosimilars and Bioanalytical Methods
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Advanced Biosensing Techniques and Applications
- Breast Cancer Treatment Studies
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Gene expression and cancer classification
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- Ferroptosis and cancer prognosis
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
- Ovarian cancer diagnosis and treatment
- Mitochondrial Function and Pathology
- 3D Printing in Biomedical Research
- RNA Research and Splicing
- Wnt/β-catenin signaling in development and cancer
- Genomics and Chromatin Dynamics
- Cell Image Analysis Techniques
- Reproductive System and Pregnancy
UPMC Hillman Cancer Center
2012-2025
University of Pittsburgh
2012-2025
University of Colorado Anschutz Medical Campus
2016-2025
Cancer Research Center
2012-2025
Magee-Womens Research Institute
2016-2025
University of Colorado Denver
2016-2024
University of Colorado Cancer Center
2020
University of Pittsburgh Medical Center
2014-2016
Huntsman Cancer Institute
2014
University of Utah
2014
Invasive lobular carcinoma (ILC) is a histologic subtype of breast cancer that frequently associated with favorable outcomes, as approximately 90% ILC express the estrogen receptor (ER). However, recent retrospective analyses suggest patients receiving adjuvant endocrine therapy may not benefit much invasive ductal carcinoma. On basis these observations, we characterized ER function and response in models. The ER-positive cell lines MDA MB 134VI (MM134) SUM44PE were used to examine...
Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported vitro models BC either before or after acquisition resistance making functional consequences difficult study. We report first discovery
Invasive lobular breast carcinoma (ILC) is a histological subtype of cancer that characterized by loss E-cadherin and high expression estrogen receptor alpha (ERα). In many cases, ILC effectively treated with adjuvant aromatase inhibitors (AIs); however, acquired AI resistance remains significant problem. To identify underlying mechanisms anti-estrogen in ILC, we recently developed six long-term estrogen-deprived (LTED) variant cell lines from the human SUM44PE (SUM44; two lines)...
Abstract Epithelial ovarian cancer (EOC) has one of the highest death to incidence ratios among all cancers. High grade serous carcinoma (HGSOC) is most common and deadliest EOC histotype due lack therapeutic options following debulking surgery platinum/taxane‐based chemotherapies. For recurrent chemosensitive HGSOC, poly(ADP)‐ribose polymerase inhibitors (PARPi; olaparib, rucaparib, or niraparib) represent an emerging treatment strategy. While PARPi are effective in homologous recombination...
Members of the cytochrome P450 (P450) family drug-metabolizing enzymes are present in human brain, and they may have important roles oxidation endogenous substrates. The polymorphic CYP2D6 is one major brain isoforms has been implicated neurodegeneration, psychosis, schizophrenia, personality traits. objective this study was to determine whether endocannabinoid arachidonoylethanolamide (anandamide) a substrate for CYP2D6. Anandamide ligand cannabinoid receptor CB1, which also activated by...
Invasive lobular carcinoma (ILC) of the breast typically presents with clinical biomarkers consistent a favorable response to endocrine therapies, and over 90 % ILC cases express estrogen receptor (ER). However, subset may be resistant suggesting that ER biology is unique in ILC. Using cell lines, we previously demonstrated regulates distinct gene expression program cells, hypothesized these ER-driven pathways modulate One potential novel pathway via Wnt ligand WNT4, critical signaling...
Abstract Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer following invasive ductal (IDC) and characterized by loss E-cadherin–mediated adherens junctions. Despite displaying unique histologic clinical features, ILC still remains a chronically understudied disease, with limited knowledge gleaned from available laboratory research models. Here we report comprehensive 2D 3D phenotypic characterization four estrogen receptor–positive human cell lines:...
Charcoal-stripped bovine serum (CSS) is a critical reagent in the study of steroid hormones. However, CSS has high lot-to-lot variability, including residual growth factor and hormone content. Assessing reporting this variability challenging but may affect experimental outcomes data reproducibility. We hypothesized that lot would endocrine response phenotypes breast cancer cells, we tested effects five individual lots on MCF-7 MDA MB 134VI (MM134) cells. Based antiestrogens cell...
Invasive lobular carcinoma (ILC) is an understudied subtype of breast cancer that requires novel therapies in the advanced setting. To study acquired resistance to endocrine therapy ILC, we have recently performed RNA-Sequencing on long-term estrogen deprived cell lines and identified FGFR4 overexpression as a top druggable target. Here, show expression also increases dramatically endocrine-treated distant metastases, with average fold change 4.8 relative paired primary tumor for 2.4-fold...
Ovarian cancer has one of the highest deaths to incidence ratios across all cancers. Initial chemotherapy is effective, but most patients develop chemoresistant disease. Mechanisms driving clinical chemo-response or -resistance are not well-understood. However, achieving optimal surgical cytoreduction improves survival, and improved by neoadjuvant (NACT). NACT offers a window profile pre- versus post-NACT tumors, which we used identify chemotherapy-induced changes tumor microenvironment.
Abstract Purpose: High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha (ERα) in approximately 80% HGSOC and some small but promising clinical trials endocrine therapy, ERα has been understudied as a target this disease. We sought to identify hormone-responsive, ERα-dependent HGSOC. Experimental Design: characterized response cells across culture conditions [ two-dimensional (2D),...
Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver cancer's response to Fulvestrant (Fulv) treatment. Using in vitro cell lines vivo xenograft metastasis mouse models, examined the molecular mechanisms combining...
Abstract Both TP53 and ESR1 mutations occur frequently in estrogen receptor positive (ER+) metastatic breast cancers (MBC) their distinct roles cancer tumorigenesis progression are well appreciated. Recent clinical studies discovered mutual exclusivity between cancers; however, mechanisms underlying this intriguing observation remain largely understudied unknown. Here, we explored the interplay using publicly available experimental data sets. We first confirmed robust mutational six...
Porcupine O-acyltransferase (PORCN) is considered essential for Wnt secretion and signaling. However, we observed that PORCN inhibition does not phenocopy the effects of WNT4 knockdown in WNT4-dependent breast cancer cells. This suggests a unique relationship between To examine role signaling, here overexpressed or WNT3A cancer, ovarian fibrosarcoma cell lines. Conditioned media from these lines co-culture systems were used to assess dependence activity on critical proteins ligand (WLS)...
The current study evaluated associative effects of breast cancer cells with the tumor microenvironment and its influence on behavior.Formalin-fixed, paraffin-embedded tissue matched protein lysates were from two independent patient datasets (TCGA MD Anderson). Reverse-phase arrays (RPPA) utilized to create a proteomics signature define subtypes. Expression patterns cell lines normal tissues determine markers that differentially expressed in stroma cells. Protein localization stromal contents...
Invasive lobular carcinoma of the breast (ILC) is strongly estrogen-driven and represents a unique context for estrogen receptor (ER) signaling. In ILC, ER controls expression Wnt ligand WNT4, which critical endocrine response anti-estrogen resistance. However, signaling mediated by WNT4 cell type- tissue-specific, has not been explored in ILC. We utilized reverse phase protein array (RPPA) to characterize WNT4-driven ILC cells identified that mediates downstream mTOR via phosphorylation S6...
Abstract As one of the most successful cancer therapeutic targets, estrogen receptor-α (ER/ESR1) has been extensively studied over past few decades. Sequencing technological advances have enabled genome-wide analysis ER action. However, comparison individual studies is limited by different experimental designs, and meta-analyses are available. Here, we established EstroGene database through unified processing data from 246 experiments including 136 transcriptomic, cistromic, epigenetic...
Efavirenz-based HIV therapy is associated with breast hypertrophy and gynaecomastia. Here, we tested the hypothesis that efavirenz induces gynaecomastia through direct binding modulation of oestrogen receptor (ER).To determine effect on growth, oestrogen-dependent, ER-positive cancer cell lines MCF-7, T47D ZR-75-1 were treated under oestrogen-free conditions in presence or absence anti-oestrogen ICI 182,780. Cells 17β-oestradiol 182,780 served as positive negative controls, respectively....