A5005465402- Cancer Cells and Metastasis
- Biomarkers in Disease Mechanisms
- Advanced Breast Cancer Therapies
- Nutrition, Genetics, and Disease
- MicroRNA in disease regulation
- DNA Repair Mechanisms
- Ferroptosis and cancer prognosis
- PARP inhibition in cancer therapy
- Breast Cancer Treatment Studies
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Cancer Research and Treatments
- Wnt/β-catenin signaling in development and cancer
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- Genetic Neurodegenerative Diseases
- Protein Kinase Regulation and GTPase Signaling
- Fibroblast Growth Factor Research
- Science, Research, and Medicine
- Glutathione Transferases and Polymorphisms
- BRCA gene mutations in cancer
- Brain Metastases and Treatment
- Cancer Risks and Factors
- Pancreatic and Hepatic Oncology Research
- Immune cells in cancer
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2018-2024
The Ohio State University
2015-2024
The Ohio State University Wexner Medical Center
2018-2024
West Virginia University
2020-2021
Neuroscience Institute
2020
Creative Commons
2020
West Virginia University Hospitals
2020
Case Western Reserve University
2013-2014
University School
2013-2014
Resistance to genotoxic therapies is a primary cause of treatment failure and tumor recurrence. The underlying mechanisms that activate the DNA damage response (DDR) allow cancer cells escape lethal effects remain unclear. Here, we uncover an unexpected mechanism through which pyruvate kinase M2 (PKM2), highly expressed PK isoform in master regulator metabolic reprogramming, integrates with DDR directly promote double-strand break (DSB) repair. In ionizing radiation oxidative stress, ATM...
Engineered oncolytic viruses are used clinically to destroy cancer cells and have the ability boost anticancer immunity. Phosphatase tensin homolog deleted on chromosome 10 loss is common across a broad range of malignancies, implicated in immune escape. The N-terminally extended isoform, phosphatase alpha (PTENα), regulates cellular functions including protein kinase B signaling mitochondrial adenosine triphosphate production. Here we constructed HSV-P10, replicating, PTENα expressing...
The extracellular matrix (ECM) is critical for mammary ductal development and differentiation, but how fibroblasts regulate ECM remodeling remains to be elucidated. Herein, we used a mouse genetic model activate platelet derived growth factor receptor-alpha (PDGFRα) specifically in the stroma. Hyperactivation of PDGFRα stroma severely hindered pubertal morphogenesis, did not interrupt lobuloalveolar differentiation program. Increased stromal signaling induced fat pad fibrosis with...
The contribution of the microenvironment to pancreatic acinar-to-ductal metaplasia (ADM), a preneoplastic transition in oncogenic Kras-driven cancer progression, is currently unclear. Here we show that disruption paracrine Hedgehog signaling via genetic ablation Smoothened (Smo) stromal fibroblasts Kras(G12D) mouse model increased ADM. Smo-deleted had higher expression transforming growth factor-α (Tgfa) mRNA and secreted levels TGFα, leading activation EGFR acinar cells mechanism involved...
The organization of the extracellular matrix has a profound impact on cancer development and progression. becomes aligned throughout tumor progression, providing "highways" for cell invasion. Aligned is associated with breast density negative prognostic factor in several cancers; however, underlying mechanisms regulating this reorganization remain poorly understood. Deletion suppressor Pten stroma was previously shown to promote expansion However, it unknown if PTEN also regulated...
The contribution of the tumor microenvironment to pancreatic ductal adenocarcinoma (PDAC) development is currently unclear. We therefore examined consequences disrupting paracrine Hedgehog (HH) signaling in PDAC stroma. Herein, we show that ablation key HH gene Smoothened (Smo) stromal fibroblasts led increased proliferation cells. Furthermore, Smo deletion resulted proteasomal degradation suppressor PTEN and activation oncogenic protein kinase B (AKT) fibroblasts. An unbiased proteomic...
PARP inhibitors (PARPi) are potentially effective therapeutic agents capable of inducing synthetic lethality in tumors with deficiencies homologous recombination (HR)-mediated DNA repair such as those carrying BRCA1 mutations. However, BRCA mutations rare, the majority proficient HR repair, and thus most resistant to PARPi. Previously, we observed that ionizing radiation (IR) initiates cytoplasmic translocation leading suppression HR-mediated induction PARPi wild-type HR-proficient tumor...
Abstract Background Unlike other breast cancer subtypes that may be treated with a variety of hormonal or targeted therapies, there is need to identify new, effective targets for triple-negative (TNBC). It has recently been recognized membrane potential depolarized in cells. The primary objective the study explore whether hyperpolarization induced by opening potassium channels provide new strategy treatment TNBC. Methods Breast datasets cBioPortal genomics was used search ion channel gene...
Glioblastoma cells co-cultured with astrocytes in col-HA hydrogels exhibit changes migration patterns. 3D vitro models using ECM mimetic materials can be used to analyze glioma-astrocyte crosstalk.
Protein kinase C beta (PKCβ) expression in breast cancer is associated with a more aggressive tumor phenotype, yet the mechanism for how PKCβ pro-tumorigenic this disease still unclear. Interestingly, while it known that mediates angiogenesis, immunity, fibroblast function and adipogenesis, all components of mammary microenvironment (TME), no study to date has investigated whether stromal functionally relevant cancer. Herein, we evaluate mouse virus-polyoma middle T-antigen (MMTV-PyMT)...
Abstract Background Triple-negative breast cancer (TNBC) is a heterogeneous disease and we have previously shown that rapid relapse of TNBC associated with distinct sociodemographic features. We hypothesized versus late in also defined by clinical genomic features primary tumors. Methods Using three publicly-available datasets, identified 453 patients diagnosed adequate follow-up to be characterized as ‘rapid relapse’ (rrTNBC; distant or death ≤2 years diagnosis), ‘late (lrTNBC; > 2...
Abstract The importance of the tumor–associated stroma in cancer progression is clear. However, it remains uncertain whether early events are capable initiating breast tumorigenesis. Here, we show that mammary glands non-tumor bearing mice, stromal-specific phosphatase and tensin homolog ( Pten ) deletion invokes radiation-induced genomic instability neighboring epithelium. In these animals, a single dose whole-body radiation causes focal lobuloalveolar hyperplasia through paracrine...
Pancreatic cancer is an aggressive disease with a 5 year survival rate of 13%. This poor attributed, in part, to limited and ineffective treatments for patients metastatic disease, highlighting need identify molecular drivers pancreatic target more effective treatment. CD200 glycoprotein that interacts the receptor CD200R elicits immunosuppressive response. Overexpression has been associated differential outcomes, depending on tumor type. In context cancer, we have previously reported...
Abstract Background Breast cancer (BC) is the most common in women and leading cause of cancer-associated mortality women. In particular, triple-negative BC (TNBC) has highest rate due large part to lack targeted treatment options for this subtype. Thus, there an urgent need identify new molecular targets TNBC treatment. RALA RALB are small GTPases implicated growth metastasis a variety cancers, although little known their roles BC. Methods The necessity tumor were evaluated vivo using...
Expression of FOXC1, a forkhead box transcription factor, correlates with the human basal-like breast cancer (BLBC) subtype, and functional analyses have revealed its importance for in vitro invasiveness BLBC cells. Women diagnosed this tumor subtype poorer outcome because lack targeted therapies; thus, continued investigation factors driving these tumors is critical to uncover novel therapeutic targets. Several processes that dictate normal mammary morphogenesis parallel progression,...