A5063733765- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cell Adhesion Molecules Research
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Circular RNAs in diseases
- Advanced biosensing and bioanalysis techniques
- Cancer-related molecular mechanisms research
- Nanoparticle-Based Drug Delivery
- Melanoma and MAPK Pathways
- Protein Kinase Regulation and GTPase Signaling
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Angiogenesis and VEGF in Cancer
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Research Studies
- HER2/EGFR in Cancer Research
- Genomics and Chromatin Dynamics
- Axon Guidance and Neuronal Signaling
- Ferroptosis and cancer prognosis
- ATP Synthase and ATPases Research
- Immune cells in cancer
- Caveolin-1 and cellular processes
- Biochemical and Molecular Research
- bioluminescence and chemiluminescence research
UNC Lineberger Comprehensive Cancer Center
2020-2025
Segeberger Kliniken
2022
University of North Carolina at Chapel Hill
2014-2021
University of North Carolina Health Care
2016-2017
Institut thématique Génétique, génomique et bioinformatique
2016
BACKGROUND. The KRAS proto-oncogene is among the most frequently mutated genes in cancer, yet for 40 years it remained an elusive therapeutic target. Recently, allosteric inhibitors that covalently bind to G12C mutations have been approved use lung adenocarcinomas. Although responses are observed, they often short-lived, thus making in-depth characterization of mechanisms resistance paramount importance.
Lung cancer is the leading cause of cancer-related deaths worldwide, and lung squamous carcinomas (LUSC) represent about 30% cases. Molecular aberrations in adenocarcinomas have allowed for effective targeted treatments, but corresponding therapeutic advances LUSC not materialized. However, immune checkpoint inhibitors sub-populations patients led to exciting responses. Using computational analyses The Cancer Genome Atlas, we identified a subset tumors characterized by dense infiltration...
Despite being among the most common oncogenes in human cancer, to date, there are no effective clinical options for inhibiting KRAS activity. We investigated whether systemically delivered siRNAs have therapeutic potential KRAS-mutated cancer models. identified siRNA sequences with notable potency knocking down expression. Using lung and colon adenocarcinoma cell lines, we assessed antiproliferative effects of silencing vitro. For vivo experiments, used a nanoliposomal delivery platform,...
In tumors, extravascular fibrin forms provisional scaffolds for endothelial cell (EC) growth and motility during angiogenesis. We report that fibrin-mediated angiogenesis was inhibited tumor delayed following postnatal deletion of Tgfbr2 in the endothelium Cdh5-CreERT2 Tgfbr2fl/fl mice (Tgfbr2iECKO mice). ECs from Tgfbr2iECKO failed to upregulate fibrinolysis inhibitor plasminogen activator 1 (Serpine1, also known as PAI-1), due part uncoupled TGF-β-mediated suppression miR-30c. Bypassing...
Polymeric micelle formulation of an immune modulator improves survival in a highly aggressive model non–small cell lung cancer.
The KRAS proto-oncogene encodes a small GTPase that is crucial for the activation of intracellular signaling pathways control cell proliferation, survival and differentiation. frequently mutated in cancer resulting its constitutive dysregulation downstream drive oncogenic transformation. G12V second most common mutation cancer, occurs lung, colon pancreatic cancers. However, while significant advancements have been made developing G12C, G12D pan-KRAS inhibitors, there remain no direct...
Abstract Lung squamous carcinoma (LUSC) is a highly metastatic disease with poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting circular RNA (circRNA), CDR1as. Although the putative function of circRNA through miRNA sponging, more potently silenced axis CDR1as and its antisense transcript, cerebellar degeneration related protein 1 (CDR1). Silencing or CDR1 significantly inhibited metastases was sufficient to promote migration...
Oncogenic mutations in the KRAS gene are well-established drivers of cancer. While recently developed KRASG12C inhibitors offer a targeted therapy and have shown success clinic, represents only 11% all mutations. Current therapeutic approaches for other both indirect nonmutant-selective, largely focusing on inhibition downstream effectors such as MAP kinases. Inhibition signaling results system-wide down-modulation respective targets, raising concerns about systemic cell toxicity. Here, we...
Many new drug development candidates are highly lipophilic compounds with low water solubility. This constitutes a formidable challenge for the use of such cancer therapy, where high doses and intravenous injections needed (Di et al., 2012). Here, we present poly(2-oxazoline) polymer (POx)-based nanoformulation strategy to solubilize deliver hydrophobic drugs. POx micelles prepared by simple thin-film hydration method. In this method, dissolved in common solvent allowed mix, following which...
Our recent ERK inhibitor analyses in pancreatic ductal adenocarcinoma (PDAC) demonstrated that MYC protein loss is a marker of sensitivity, and indicated resistant cell lines possess KRASdependent, ERK-independent mechanisms maintaining levels. In seeking to identify these mechanisms, we first determined the signaling networks by which mutant KRAS regulates MYC. Acute suppression caused rapid proteasome-dependent protein, through both ERK1/2-dependent -independent mechanisms. Surprisingly,...
Angiogenesis is the growth of new vessels from pre-existing vasculature and an important component many biological processes, including embryogenesis development, wound healing, tumor metastasis, ocular cardiovascular diseases. Effective in vitro models that recapitulate biology angiogenesis are needed to appropriately study this process identify mechanisms regulation can be ultimately targeted for novel therapeutic strategies. The bead assay has been previously demonstrated multiple stages...
Abstract The KRAS proto-oncogene encodes a small GTPase that is crucial for the activation of intracellular signaling pathways control cell proliferation, survival and differentiation. frequently mutated in cancer resulting its constitutive dysregulation downstream drive oncogenic transformation. G12V second most common mutation cancer, occurs lung, colon pancreatic cancers. However, while significant advancements have been made developing G12C, G12D pan-KRAS inhibitors, there remain no...
Angiogenesis is the growth of new vessels from pre-existing vasculature and an important component many biological processes, including embryogenesis development, wound healing, tumor metastasis, ocular cardiovascular diseases. Effective in vitro models that recapitulate biology angiogenesis are needed to appropriately study this process identify mechanisms regulation can be ultimately targeted for novel therapeutic strategies. The bead assay has been previously demonstrated multiple stages...
Abstract About 40% of the NSCLC patients have Stage IV cancer at time diagnosis. The only viable treatment options for metastatic disease are systemic chemotherapy and immunotherapy. Nonetheless, chemoresistance remains a major cause failure. New immunotherapeutic modalities such as anti-PD1 checkpoint blockade shown promise; however, response to strategies is highly variable across patients. Here, we show that our novel poly(2-oxazoline) (POx) based nanomicellar formulation Resiquimod, an...
Abstract Oncogenic mutations in the KRAS gene are well-established drivers of cancer. Promising preclinical strategies including RNA interference (RNAi) have been developed to target oncogenic function, yet a clinically effective therapy directly remains be achieved. While genetic knockdown mutant (mKRAS) with RNAi is one promising approach, current methods not mutant-selective, and thus they also decrease normal levels, raising concerns about cell toxicity. Here, we describe custom short...
Tumor xenograft models developed by transplanting human tissues or cells into immune-deficient mice are widely used to study cancer response drug candidates. However, unfit for investigating the effect of immunotherapeutic agents on host immune (Morgan, 2012). Here, we describe preparation an orthotopic, syngeneic model lung adenocarcinoma (LUAD), a subtype non-small cell (NSCLC), antitumor chemo and in immune-competent animal. The tumor is implanting 344SQ LUAD derived from metastases...
Abstract Introduction: Lung cancer is the leading cause of cancer-related deaths worldwide, and patients usually die from metastatic disease. Radiation a mainstay treatment in lung cancer, but its efficacy largely dependent on tumor perfusion. We recently found that miR-200b novel AngiomiR capable inhibiting metastasis angiogenesis while inducing vascular normalization. are investigating whether normalization with can enhance therapeutic radiation model cancer. Methods: Using cell lines, we...
Abstract Tumor-associated endothelial cells (TECs) are dysfunctional and leak fibrin which is resolved (fibrinolysis) replaced with collagen in a process that closely resembles wound healing. Because degraded perivascular also promotes angiogenesis creates scaffolds for invasive cancer cells, vascular-directed fibrinolysis solid tumors fundamental spark during tumor progression. Using miRNA screen of freshly isolated TECs, we identified TGF beta-regulated controls vascular-mediated tumors....
RTK/MAPK/PI3K pathway genes are mutated in 90% of glioblastomas.It remains unclear whether targeted inhibitor response is predicted by mutation status.We addressed this issue using isogenic, immortalized mouse and human astrocytes with without MAPK and/or PI3K mutations.MEK inhibitors showed variable potency (GSK1120212 .PD0325901 .AZD6244) vitro.Efficacy was independent mutations, but increased 2 -66 fold mutations.In contrast, efficacy (BKM120 .LY294002) 1.5-5 when MAPK, PI3K, or both were...
<div>Abstract<p>Lung squamous carcinoma (LUSC) is a highly metastatic disease with poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting circular RNA (circRNA), CDR1as. Although the putative function of circRNA through miRNA sponging, more potently silenced axis CDR1as and its antisense transcript, cerebellar degeneration related protein 1 (CDR1). Silencing or CDR1 significantly inhibited metastases was sufficient...
<div>Abstract<p>Lung squamous carcinoma (LUSC) is a highly metastatic disease with poor prognosis. Using an integrated screening approach, we found that miR-671-5p reduces LUSC metastasis by inhibiting circular RNA (circRNA), CDR1as. Although the putative function of circRNA through miRNA sponging, more potently silenced axis CDR1as and its antisense transcript, cerebellar degeneration related protein 1 (CDR1). Silencing or CDR1 significantly inhibited metastases was sufficient...