A5073060610- Estrogen and related hormone effects
- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Breast Cancer Treatment Studies
- Gene expression and cancer classification
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- S100 Proteins and Annexins
- Single-cell and spatial transcriptomics
- Congenital heart defects research
- Advanced Biosensing Techniques and Applications
- Growth Hormone and Insulin-like Growth Factors
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- FOXO transcription factor regulation
- Click Chemistry and Applications
- Immune cells in cancer
- RNA Research and Splicing
- Cancer Diagnosis and Treatment
- Wnt/β-catenin signaling in development and cancer
- Developmental Biology and Gene Regulation
- Pesticide Residue Analysis and Safety
- PARP inhibition in cancer therapy
University of Pittsburgh
2015-2025
University of Pittsburgh Medical Center
2024
UPMC Hillman Cancer Center
2015-2024
Magee-Womens Research Institute
2023-2024
Cancer Research Center
2015-2024
Monklands Hospital
2023
Precision for Medicine (United States)
2022-2023
University of Southern California
2019
Memorial Sloan Kettering Cancer Center
2019
Thermo Fisher Scientific (United States)
2012
Members of the T-box family proteins play a fundamental role in patterning developing vertebrate heart; however, precise cellular requirements for any one member and mechanism by which individual genes function remains largely unknown. In this study, we have investigated molecular relationship between two genes, Tbx5 Tbx20. We demonstrate that blocking or Tbx20 produces phenotypes display high degree similarity, as judged overall gross morphology, marker analysis cardiac physiology, implying...
Oral exposure to high concentrations of hexavalent chromium [Cr(VI)] induces intestinal redox changes, villus cytotoxicity, crypt hyperplasia, and tumors in mice. To assess the effects Cr(VI) a cell model relevant intestine, undifferentiated (proliferating) differentiated (confluent) Caco-2 cells were treated with Cr(VI), hydrogen peroxide or rotenone for 2–24 hours. DNA damage was then assessed by nuclear staining intensity 8-hydroxydeoxyguanosine (8-OHdG) phosphorylated histone variant...
Despite the critical importance of TBX5 in normal development and disease, relatively little is known about mechanisms by which functions embryonic heart. Our present studies demonstrate that necessary to control length cardiac cell cycle, with depletion leading cycle arrest late G(1)- or early S-phase. Blocking progression leads a decrease number, an alteration timing differentiation program, defects sarcomere formation, ultimately, programmed death. In these we have also established...
Therapy resistance in breast cancer is increasingly attributed to polyploid giant cells (PGCCs), which arise through whole genome doubling and exhibit heightened resilience standard treatments. Characterized by enlarged nuclei increased DNA content, these tend be dormant under therapeutic stress, driving disease relapse. Despite their critical role resistance, strategies effectively target PGCCs are limited, largely due the lack of high-throughput methods for assessing viability. Traditional...
Abstract Invasive lobular carcinoma (ILC) is responsible for 10%-15% of all invasive breast cancers and associated with worse long-term outcomes compared to the most common no special type (NST). Despite known differences between ILC NST, treatment same as stage matched NST. Therefore, identifying biological molecules that are specific can be therapeutically targeted an urgent need. In this context, we recently identified transcription factor AP2b (TFAP2B) one hypomethylated genes in NST...
Abstract Breast cancer is a heterogeneous disease with various histological subtypes. Invasive Lobular Cancer (ILC) the most common special subtype, accounting for 10-15% of all breast cancers. The pathognomonic feature ILC loss E-cadherin (CDH1), which leads to unique single-file growth pattern discohesive cells. Although ILCs show better prognostic factors than No Special Type (NST), patients have worse long-term outcomes, not well understood. has historically been understudied, in part...
Abstract The small heat shock protein Hsp27 has been shown to be involved in a diverse array of cellular processes, including stress response, chaperone activity, regulation glutathione levels, apoptotic signaling, and actin polymerization stability. Furthermore, mutation within associated with the human congenital neuropathy Charcot‐Marie Tooth (CMT) disease. is known expressed developing embryonic tissues; however, little done determine endogenous requirement for embryos. In this study, we...
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...
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...
Estrogen receptor alpha (ER/ESR1) mutations occur in 30% to 40% of endocrine resistant ER-positive (ER+) breast cancer. Forkhead box A1 (FOXA1) is a key pioneer factor mediating ER-chromatin interactions and response ER+ cancer, but its role ESR1-mutant cancer remains unclear. Our previous FOXA1 chromatin immunoprecipitation sequencing (ChIP-seq) identified large portion redistributed binding sites T47D genome-edited Y537S D538G cells. Here, we further integrated genomic profile with the...
Four veterinary drugs of dissimilar chemical structures were evaluated for environmental stability and penchant bioaccumulation. The techniques used (1) a model aquatic ecosystem (3 days) (2) feedlot (33 in which the introduced via excreta chicks or mice. was supported by metabolism cage studies to determine amount form drug excreted Considerable quantities all intact as environmentally short-lived conjugates. Diethylstilbestrol (DES) Clopidol most persistent molecules, but only DES...
Small nucleolar ribonucleoproteins (snoRNPs) are widely studied and characterized as guide RNAs for sequence-specific 2′-O-ribose methylation psuedouridylation of ribosomal RNAs. In addition, snoRNAs have also been shown to interact with some tRNAs direct alternative splicing in mRNA biogenesis. Recent advances bioinformatics resulted new algorithms able rapidly identify noncoding generally specifically genomic metagenomic sequences, resulting a rapid increase the number diversity identified...
Nitro fatty acids (NO2-FAs) are endogenously generated lipid signaling mediators from metabolic and inflammatory reactions between conjugated diene nitric oxide or nitrite-derived reactive species. NO2-FAs undergo reversible Michael addition with hyperreactive protein cysteine thiolates to induce posttranslational modifications that can impact function. Herein, we report a novel mechanism of action natural non-natural nitroalkenes structurally similar (E) 10-nitro-octadec-9-enoic acid...
Hypoxia-inducible factor-1 (HIF-1) and its most important subunit, HIF-1α, plays a central role in tumor progression by regulating genes involved cancer cell survival, proliferation metastasis. HIF-1α activity is associated with nuclear accumulation of the transcription factor regulated several mechanisms including modulation protein stability degradation. Among recent advances are discoveries that inflammation-induced cytokines growth factors affect under normoxia conditions. TNFα, major...
Macrophages are pivotal in driving breast tumor development, progression, and resistance to treatment, particularly estrogen receptor-positive (ER+) tumors, where they infiltrate the microenvironment (TME) influenced by cancer cell-secreted factors. By analyzing single-cell RNA-sequencing data from 25 ER+ we elucidated interactions between cells macrophages, correlating macrophage density with epithelial cell density. We identified that S100A11, a previously unexplored factor...
Macrophages are pivotal in driving breast tumor development, progression, and resistance to treatment, particularly estrogen receptor-positive (ER+) tumors, where they infiltrate the microenvironment (TME) influenced by cancer cell-secreted factors. By analyzing single-cell RNA sequencing data from 25 ER+ we elucidated interactions between cells macrophages, correlating macrophage density with epithelial cell density. We identified that S100A11, a previously unexplored factor...
Although the properties and functions of GABA<sub>A</sub> receptors in mammalian central nervous system have been well studied, presence significance non-neural tissues are less clear. The goal this study was to examine expression receptor α<sub>1</sub>, α<sub>2</sub>, α<sub>4</sub>, α<sub>5</sub>, β<sub>1</sub>, γ<sub>1</sub>, γ<sub>2</sub>, δ subunits kidney determine whether these coassemble form an active renal epithelial cell receptor. Using reverse transcriptase products from RNA...
Abstract Organoids serve as an important preclinical model in multiple cancers including breast cancer, demonstrating preservation of biological features and feasibility drug screening, with reasonable cost high scalability. It has been reported that patient-derived organoids (PDOs) can be robustly derived from both primary metastatic tumors, resemblance to source tissues histological, genomic, transcriptomic features, well consistency response compared xeno-transplantations or patients...
Abstract Background: Activating mutations in ERBB2 (HER2) are enriched &gt;4-fold invasive lobular carcinoma (ILC) with a rate of up to 19% metastatic ILC. ILC is histologic subtype breast cancer characterized by loss E-cadherin (CDH1), suggesting potential interaction between CDH1 and ERBB2. Recent trials have demonstrated promising single agent efficacy using the irreversible pan-HER tyrosine kinase inhibitor (TKI), neratinib, patients mutant However, further studies on combination...