A5032122099- Cancer, Lipids, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Cancer Mechanisms and Therapy
- Cholesterol and Lipid Metabolism
- CAR-T cell therapy research
- Glioma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Metabolomics and Mass Spectrometry Studies
- Autophagy in Disease and Therapy
- Cytokine Signaling Pathways and Interactions
- Immunotherapy and Immune Responses
- Drug Transport and Resistance Mechanisms
- Cardiac Arrhythmias and Treatments
- Protein Degradation and Inhibitors
- Cardiac pacing and defibrillation studies
- Cancer, Hypoxia, and Metabolism
- Cancer Treatment and Pharmacology
- Pharmacogenetics and Drug Metabolism
- Cardiac electrophysiology and arrhythmias
- Cancer Immunotherapy and Biomarkers
- Radiopharmaceutical Chemistry and Applications
- Ubiquitin and proteasome pathways
- Ferroptosis and cancer prognosis
City Of Hope National Medical Center
2018-2024
University of Kansas Medical Center
2020-2024
The University of Kansas Cancer Center
2022-2024
University of Kansas
2022-2024
Beckman Research Institute
2019-2024
City of Hope
2019-2024
University Medical Center
2021
University Hospital and Clinics
2021
National Cancer Center
2020
University of California, San Francisco
2003-2013
Glioblastoma (GBM) is the most common malignant primary brain tumor of adults and one lethal all cancers. Epidermal growth factor receptor (EGFR) mutations (EGFRvIII) phosphoinositide 3-kinase (PI3K) hyperactivation are in GBM, promoting survival, including through sterol regulatory element-binding protein 1 (SREBP-1)-dependent lipogenesis. The role cholesterol metabolism GBM pathogenesis, its association with EGFR/PI3K signaling, potential therapeutic targetability unknown. In our...
Inhibitors of fatty acid signaling promote apoptosis in glioblastoma cells with highly active EGFR signaling.
Although it is known that mTOR complex 2 (mTORC2) functions upstream of Akt, the role this protein kinase in cancer not well understood. Through an integrated analysis cell lines, vivo models, and clinical samples, we demonstrate mTORC2 frequently activated glioblastoma (GBM), most common malignant primary brain tumor adults. We show activating epidermal growth factor receptor (EGFR) mutation (EGFRvIII) stimulates activity, which partially suppressed by PTEN. signaling promotes GBM survival...
We determined the x-ray structure of bovine aquaporin 0 (AQP0) to a resolution 2.2 Å. The this eukaryotic, integral membrane protein suggests that selectivity AQP0 for water transport is based on identity and location signature amino acid residues are hallmarks water-selective arm AQP family proteins. Furthermore, channel lumen narrowed only by two, quasi-2-fold related tyrosine side chains might account reduced conductance relative other AQPs. functionally open passage because there eight...
Abstract The sterol regulatory element-binding proteins (SREBP) are key transcriptional regulators of lipid metabolism and cellular growth. It has been proposed that SREBP signaling regulates growth through its ability to drive biosynthesis. Unexpectedly, we find loss activity inhibits cancer cell viability by uncoupling fatty acid synthesis from desaturation. Integrated profiling metabolic flux analysis revealed cells with attenuated maintain long-chain saturated synthesis, while losing...
Acquired resistance to tyrosine kinase inhibitors (TKI) represents a major challenge for personalized cancer therapy. Multiple genetic mechanisms of acquired TKI have been identified in several types human cancer. However, the possibility that cells may also evade treatment by co-opting physiologically regulated receptors has not addressed. Here, we show first example this alternate mechanism brain tumors showing EGF receptor (EGFR)-mutant glioblastomas (GBMs) EGFR TKIs transcriptionally...
Abstract Purpose: mTOR pathway hyperactivation occurs in approximately 90% of glioblastomas, but the allosteric inhibitor rapamycin has failed clinic. Here, we examine efficacy newly discovered ATP-competitive kinase inhibitors CC214-1 and CC214-2 glioblastoma, identifying molecular determinants response mechanisms resistance, develop a pharmacologic strategy to overcome it. Experimental Design: We conducted vitro vivo studies glioblastoma cell lines an intracranial model to: determine...
A common mutation of the epidermal growth factor receptor in glioma is de2-7EGFR (or EGFRvIII). Glioma cells expressing contain an intracellular pool with high levels mannose glycosylation, which consistent delayed processing. We now show that this delay occurs Golgi complex. Low were also seen within mitochondria. Src activation dramatically increased amount mitochondrial de2-7EGFR, whereas its pharmacological inhibition caused a significant reduction. Because phosphorylated by at Y845, we...
Background: M5A is a humanized monoclonal antibody (mAb) directed against carcinoembryonic antigen (CEA) The purpose of this first in human phase I dose-escalation trial was to characterize the toxicities and determine maximum tolerated dose (MTD) yttrium-90 (90Y)-DOTA-M5A as single agent combination with gemcitabine (gem). Methods: Patients advanced metastatic CEA-producing malignancies who had progressed on standard therapies were administered indium-111 (111In)-DOTA-M5A. If tumor...
Standard-of-care treatment for Glioblastoma Multiforme (GBM) is comprised of surgery and adjuvant chemoradiation. Chimeric Antigen Receptor (CAR) T cell therapy has demonstrated disease-modifying activity in GBM holds great promise. Radiation, a standard-of-care GBM, well-known immunomodulatory properties may overcome the immunosuppressive tumor microenvironment (TME); however, radiation dose optimization integration with CAR not well defined. Murine immunocompetent models were treated...
An IL-4 antagonist was designed based on structural and biochemical analysis of unbound in complex with its high-affinity receptor (IL-4Rα). Our design strategy sought to capture a protein–protein interaction targeting the high affinity that has for IL-4Rα. This impact due potential relevance IL-4Rα as drug target treatment asthma. To mimic binding surface, critical side chains were identified, these transplanted onto previously characterized, de novo -designed four-helix protein called...
Objectives: The treatment of choice for locally advanced cervical cancer is definitive chemoradiation (CRT). Hysterectomy not indicated due to higher-rates cut-through resections leaving gross disease behind, requiring additional therapy with increasing morbidity and no benefit in overall survival (OS). objectives this study were determine factors associated hysterectomies evaluate OS outcomes. Materials Methods: National Cancer Database (NCDB) was queried patients 18 years older clinical...
Key Teaching Points•Cardiac stereotactic body radiotherapy (SBRT) is a salvage option for refractory ventricular tachycardia with structural heart disease.•WiSE-CRT (Wireless Stimulation Endocardially Cardiac Resynchronization Therapy; EBR Systems, Sunnyvale, CA) promising leadless left endocardial pacing modality cardiac resynchronization therapy.•We present proof-of-concept case of successful SBRT in patient WiSE CRT.•In presence implantable electronic device (CIED), especially CRT...