A5018027470- Estrogen and related hormone effects
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Breast Cancer Treatment Studies
- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- Nutrition, Genetics, and Disease
- Growth Hormone and Insulin-like Growth Factors
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- S100 Proteins and Annexins
- Single-cell and spatial transcriptomics
- Heat shock proteins research
- Endoplasmic Reticulum Stress and Disease
- Click Chemistry and Applications
- Advanced Biosensing Techniques and Applications
- Protein Degradation and Inhibitors
- Ion channel regulation and function
- Cancer Genomics and Diagnostics
- Wnt/β-catenin signaling in development and cancer
- Ion Transport and Channel Regulation
- bioluminescence and chemiluminescence research
- Global Cancer Incidence and Screening
- Advanced biosensing and bioanalysis techniques
UPMC Hillman Cancer Center
2021-2024
University of Pittsburgh
2015-2024
Magee-Womens Research Institute
2021-2024
Cancer Research Center
2021-2023
University of Pittsburgh Medical Center
2020-2022
Children's Hospital of Pittsburgh
2020
Stamatopoulos and Associates (Greece)
2018
Constitutively active estrogen receptor α (ER/ESR1) mutations have been identified in approximately one-third of ER+ metastatic breast cancers. Although these are known as mediators endocrine resistance, their potential role promoting disease has not yet mechanistically addressed. In this study, we show the presence ESR1 exclusively distant but local recurrences five independent cancer cohorts. concordance with transcriptomic profiling ESR1-mutant tumors, genome-edited Y537S and D538G-mutant...
Phenylalanine hydroxylase–deficient (PAH-deficient) phenylketonuria (PKU) results in systemic hyperphenylalaninemia, leading to neurotoxicity with severe developmental disabilities. Dietary phenylalanine (Phe) restriction prevents the most deleterious effects of but adherence diet is poor adult and adolescent patients, resulting characteristic neurobehavioral phenotypes. Thus, an urgent need exists for new treatments. Additionally, rodent models PKU do not adequately reflect neurocognitive...
In the kidney, epithelial sodium channel (ENaC) regulates blood pressure through control of and volume homeostasis, in lung, ENaC airway alveolar fluids. is a heterotrimer homologous α-, β- γ-subunits, assembles endoplasmic reticulum (ER) before it traffics to functions at plasma membrane. Improperly folded or orphaned subunits are subject ER quality targeted for ER-associated degradation (ERAD). We previously established that conserved, lumenal, molecular chaperone, Lhs1/GRP170, selects...
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...
Molecular chaperones, such as Hsp70, prevent proteotoxicity and maintain homeostasis. This is perhaps most evident in cancer cells, which overexpress Hsp70 thrive even when harboring high levels of misfolded proteins. To define the response to proteotoxic challenges, we examined adaptive responses breast cells presence an inhibitor. We discovered that bin into distinct classes based on inhibitor sensitivity. Strikingly, resistant have higher autophagy levels, was maximally activated only...
No special-type breast cancer [NST; commonly known as invasive ductal carcinoma (IDC)] and lobular (ILC) are the two major histological subtypes of with significant differences in clinicopathological molecular characteristics. The defining pathognomonic feature ILC is loss cellular adhesion protein, E-cadherin (CDH1). We have previously shown that functions a negative regulator IGF1R propose sensitizes cells to growth factor signaling thus alters their sensitivity factor-signaling inhibitors...
Abstract Breast cancer is a leading cause of female mortality and despite advancements in personalized therapeutics, metastatic disease largely remains incurable due to drug resistance. The estrogen receptor (ER, ESR1) expressed two-thirds all breast cancer, under endocrine stress, somatic ESR1 mutations arise approximately 30% cases that result We others reported fusions as mechanism ER-mediated ER fusions, which retain the activation function 1- DNA-binding domains, harbor exons 1 6 fused...
The extracellular regions of epithelial Na+ channel subunits are highly ordered structures composed domains formed by α helices and β strands. Deletion the peripheral knuckle domain subunit in αβγ trimer results activation, reflecting an increase open probability due to a loss inhibitory effect external (Na+ self-inhibition). In contrast, deletion either or γ within dramatically reduces function surface expression, impairs maturation. We systematically mutated individual residues assessed...
Transmembrane proteins have unique requirements to fold and integrate into the endoplasmic reticulum (ER) membrane. Most notably, transmembrane must in three separate environments: extracellular domains oxidizing environment of ER lumen, (TMDs) within lipid bilayer, cytosolic reducing cytosol. Moreover, each region is acted upon by a set chaperones monitored components associated quality control machinery that identify misfolded compartment. One factor lumenal Hsp70-like chaperone, Lhs1. Our...
The epithelial Na
Studies in the yeast Saccharomyces cerevisiae have helped define mechanisms underlying activity of ubiquitin–proteasome system (UPS), uncover proteasome assembly pathway, and link UPS to maintenance cellular homeostasis. However, spectrum substrates is incompletely defined, even though multiple techniques—including MS—have been used. Therefore, we developed a substrate trapping proteomics workflow identify previously unknown substrates. We first generated strain with an epitope tagged...
<div>Abstract<p>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,...