Clifford Stephan

ORCID: 0000-0003-0657-6484
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About
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Research Areas
  • Melanoma and MAPK Pathways
  • PI3K/AKT/mTOR signaling in cancer
  • Glioma Diagnosis and Treatment
  • Colorectal Cancer Treatments and Studies
  • Cancer-related Molecular Pathways
  • Flavonoids in Medical Research
  • Cancer Genomics and Diagnostics
  • Microtubule and mitosis dynamics
  • Cancer, Hypoxia, and Metabolism
  • Cancer Cells and Metastasis
  • Cancer Research and Treatments
  • Synthesis and biological activity
  • Lung Cancer Research Studies
  • Computational Drug Discovery Methods
  • Epigenetics and DNA Methylation
  • PARP inhibition in cancer therapy
  • Protein Degradation and Inhibitors
  • DNA Repair Mechanisms
  • Neuroblastoma Research and Treatments
  • Angiogenesis and VEGF in Cancer
  • Radiation Therapy and Dosimetry
  • Ubiquitin and proteasome pathways
  • Ovarian cancer diagnosis and treatment
  • 3D Printing in Biomedical Research
  • Lung Cancer Treatments and Mutations

Texas A&M Health Science Center
2016-2025

Texas A&M University
2014-2025

High Throughput Biology (United States)
2020-2025

Mitchell Institute
2022-2024

Translational Research in Oncology
2023

Sun Yat-sen University
2021

Texas A&M University System
2019-2020

The University of Texas Health Science Center at Houston
2009-2018

Houston Methodist
2016

The University of Texas MD Anderson Cancer Center
2014

Abstract. Vascular endothelial growth factor (VEGF) is a cytokine that potently stimulates angiogenesis, microvascular hyperpermeability, and endothelium-dependent vasodilation, effects are largely mediated by nitric oxide synthase (eNOS). The expression of VEGF pronounced in glomerular visceral epithelial cells, but its function renal physiology pathophysiology unknown. upregulated high ambient glucose concentrations several cell types vitro glomeruli diabetic rats. To assess the role early...

10.1681/asn.v125993 article EN Journal of the American Society of Nephrology 2001-05-01

The purpose of these experiments was to investigate a potential role for vascular endothelial growth factor (VEGF) in mediating dysfunction induced by increased glucose flux via the sorbitol pathway. Skin chambers were mounted on backs Sprague-Dawley rats and 1 wk later, granulation tissue chamber exposed twice daily 7 d 5 mM glucose, 30 or presence absence neutralizing VEGF antibodies. Albumin permeation blood flow two- three-fold sorbitol; increases prevented coadministration Blood albumin...

10.1172/jci119392 article EN Journal of Clinical Investigation 1997-05-01

Abstract The physical properties of particles used in radiation therapy, such as protons, have been well characterized and their dose distributions are superior to photon-based treatments. However, proton therapy may also inherent biologic advantages that not capitalized on. Unlike photon beams, the linear energy transfer (LET) hence effectiveness particle beams varies along beam path. Selective placement areas high could enhance tumor cell kill simultaneously spare normal tissues. previous...

10.1038/srep09850 article EN cc-by Scientific Reports 2015-05-18

Abstract Background Triple-negative breast cancers (TNBCs), which lack receptors for estrogen, progesterone, and amplification of epidermal growth factor receptor 2, are highly aggressive. Consequently, patients diagnosed with TNBCs have reduced overall disease-free survival rates compared to other subtypes cancer. characterized by the presence cancer cells mesenchymal properties, indicating that epithelial transition (EMT) plays a major role in progression this disease. The EMT program has...

10.1186/s13058-019-1125-0 article EN cc-by Breast Cancer Research 2019-03-07

Protein/protein interactions (PPI) play crucial roles in neuronal functions. Yet, their potential as drug targets for brain disorders remains underexplored. The fibroblast growth factor 14 (FGF14)/voltage-gated Na+ channel 1.6 (Nav1.6) complex regulates excitability of medium spiny neurons (MSN) the nucleus accumbens (NAc), a central hub reward circuitry that controls motivated behaviors. Here, we identified compound 1028 (IUPAC: ethyl...

10.1038/s41467-024-55554-7 article EN cc-by-nc-nd Nature Communications 2025-01-02

Abstract. Long-term peritoneal dialysis is associated with the development of functional and structural alterations membrane. exposure to high glucose concentrations in conventional dialysate has been implicated pathogenesis hyperpermeability neoangiogenesis. Vascular endothelial growth factor (VEGF) an endothelial-specific that potently stimulates microvascular permeability proliferation. High upregulates VEGF expression various cell types tissues. This study investigated whether plays a...

10.1681/asn.v1281734 article EN Journal of the American Society of Nephrology 2001-08-01

The LKB1/AMPK pathway plays a major role in cellular homeostasis and tumor suppression. Down-regulation of occurs several human cancers has been implicated metabolic diseases. However, the precise upstream regulation LKB1-AMPK is largely unknown. Here, we report that AMPK activation by LKB1 regulated tankyrases. Tankyrases interact with ribosylate LKB1, promoting its K63-linked ubiquitination an E3 ligase RNF146, which blocks LKB1/STRAD/MO25 complex formation activation. tankyrase inhibitors...

10.1038/s41467-019-12377-1 article EN cc-by Nature Communications 2019-09-25

Abstract Motivation Drug combinations that simultaneously suppress multiple cancer driver signaling pathways increase therapeutic options and may reduce drug resistance. We have developed a computational systems biology tool, DrugComboExplorer, to identify predict synergistic by integrating the knowledge embedded in vast amounts of available pharmacogenomics omics data. Results This tool generates networks processing DNA sequencing, gene copy number, methylation RNA-seq data from individual...

10.1093/bioinformatics/btz109 article EN cc-by-nc Bioinformatics 2019-02-15

Abstract Replication stress is a characteristic feature of cancer cells, which resulted from sustained proliferative signaling induced by activation oncogenes or loss tumor suppressors. In oncogene-induced replication manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized cells to repair DSBs homologous recombination (HR). order overcome and survive, often require enhanced HR capacity. Therefore, the key link between...

10.1038/oncsis.2017.15 article EN cc-by Oncogenesis 2017-04-17

Abstract The epithelial-mesenchymal transition (EMT) has been implicated in conferring stem cell properties and therapeutic resistance to cancer cells. Therefore, identification of drugs that can reprogram EMT may provide new strategies. Here, we report cells derived from claudin-low mammary tumors, a mesenchymal subtype triple-negative breast cancer, exhibit distinctive organoid structure with extended “spikes” 3D matrices. Upon miR-200 induced mesenchymal-epithelial (MET), the organoids...

10.1038/s41467-021-24545-3 article EN cc-by Nature Communications 2021-07-12

Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and rapidly fatal interstitial lung disease marked by the replacement of alveoli with dense fibrotic matrices. Although mechanisms initiating IPF remain unclear, rare common alleles genes expressed in epithelia, combined aging, contribute to risk for this condition. Consistently, single-cell RNA sequencing (scRNA-seq) studies have identified basal cell heterogeneity that might be pathogenic. We used cloning technologies...

10.1126/scitranslmed.abp9528 article EN Science Translational Medicine 2023-04-26

In the current situation of weak drug pipelines, impending patent expiration several blockbuster drugs, industry consolidation and changing business models that target special diseases like cancer, diabetes, Alzheimer's obesity, pharmaceutical is under intense pressure to generate a strong pipeline distinguished by better productivity, diversity cost effectiveness. The goal discovering high-quality leads in initial stages development cycle, minimize costs associated with failures at later...

10.1517/17460440903190961 article EN Expert Opinion on Drug Discovery 2009-08-20

Extensive spontaneous DNA damage from oncogene-induced replication stress is ubiquitous in precancerous lesions. While this induces differentiation, senescence, or apoptosis normal cells, defects response (RSR) allow cells to continue proliferating, ultimately leading early tumorigenesis. Using systems-level approaches, we developed a defect gene signature that predicted risk of cancer development hyperplastic Intriguingly, found rewire non-malignant into stem cell (CSC)-like state, and...

10.1016/j.celrep.2018.04.068 article EN cc-by-nc-nd Cell Reports 2018-05-01

Abstract Primary and acquired drug resistance imposes a major threat to achieving optimized clinical outcomes during cancer treatment. Aberrant changes in epigenetic modifications are closely involved of tumor cells. Using BET inhibitor (BETi) resistant leukemia cells as model system, we demonstrated herein that genome-wide enhancer remodeling played pivotal role driving therapeutic via compensational re-expression pro-survival genes. Capitalizing on the CRISPR interference technology,...

10.1038/s41467-020-14604-6 article EN cc-by Nature Communications 2020-02-06

Abstract Much has been written and said about the promise excitement of microphysiological systems, miniature devices that aim to recreate aspects human physiology on a chip. The rapid explosion offerings persistent publicity placed high expectations both product manufacturers regulatory agencies adopt data. Inevitably, discussions where this technology fits in chemical testing paradigms are ongoing. Some end-users became early adopters, whereas others have taken more cautious approach...

10.1093/toxsci/kfac061 article EN Toxicological Sciences 2022-06-11

TP 53-mutant acute myeloid leukemia (AML) remains the ultimate therapeutic challenge. Epichaperomes, formed in malignant cells, consist of heat shock protein 90 (HSP90) and associated proteins that support maturation, activity, stability oncogenic kinases transcription factors including mutant p53. High-throughput drug screening identified HSP90 inhibitors as top hits isogenic TP53-wild-type (WT) -mutant AML cells. We detected epichaperomes cells stem/progenitor with TP53 mutations but not...

10.1182/blood.2022019047 article EN cc-by-nc-nd Blood 2023-06-20

Understanding the mechanisms by which tumors adapt to therapy is critical for developing effective combination therapeutic approaches improve clinical outcomes patients with cancer.To identify promising and clinically actionable targets managing colorectal cancer (CRC), we conducted a patient-centered functional genomics platform that includes approximately 200 genes paired this high-throughput drug screen 262 compounds in four patient-derived xenografts (PDXs) from CRC.Both screening...

10.1053/j.gastro.2021.03.022 article EN cc-by-nc-nd Gastroenterology 2021-03-19

Abstract Conditional overexpression of histone reader Tri partite m otif containing protein 24 (TRIM24) in mouse mammary epithelia ( Trim24 COE ) drives spontaneous development carcinosarcoma tumors, lacking ER, PR and HER2. Human carcinosarcomas or metaplastic breast cancers (MpBC) are a rare, chemorefractory subclass triple-negative (TNBC). Comparison morphology, TRIM24 levels derived gene signature reveals strong correlation with human MpBC tumors patient-derived xenograft (PDX) models....

10.1038/s41467-021-25650-z article EN cc-by Nature Communications 2021-09-10

High-throughput viability screens are commonly used in the identification and development of chemotherapeutic drugs. These systems rely on fidelity cellular model to recapitulate drug response that occurs vivo. In recent years, there has been an expansion utilization patient-derived materials as well advanced cell culture techniques, such multi-cellular tumor organoids, further enhance translational relevance systems. Simple quantitative analysis remains a challenge, primarily due...

10.1016/j.slasd.2022.03.004 article EN cc-by-nc-nd SLAS DISCOVERY 2022-03-19

The choice of appropriate physical quantities to characterize the biological effects ionizing radiation has evolved over time coupled with advances in scientific understanding. basic hypothesis dosimetry is that energy deposited by initiates all consequences exposure a sample (e.g., DNA damage, reproductive cell death). Physical defined deposition have included dose, measure mean imparted per unit mass target, and linear transfer (LET), distance charged particles traverse medium. primary...

10.1038/s41598-024-73619-x article EN cc-by-nc-nd Scientific Reports 2024-10-24

Separase is an endopeptidase that cleaves cohesin subunit Rad21, facilitating the repair of DNA damage during interphase and resolution sister chromatid cohesion at anaphase. activity negatively regulated by securin Cdk1-cyclin B in vivo. overexpression reported a broad range human tumors, its mouse models results tumorigenesis. To elucidate further mechanism separase function to test if inhibition overexpressed can be used as strategy inhibit tumor-cell proliferation, small-molecule...

10.1177/1087057114520972 article EN cc-by-nc-nd SLAS DISCOVERY 2014-02-14
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