A5027603795- Nuclear Structure and Function
- Cell death mechanisms and regulation
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Heat shock proteins research
- Genomics and Chromatin Dynamics
- Cancer Research and Treatments
- Cancer-related Molecular Pathways
- Lung Cancer Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Telomeres, Telomerase, and Senescence
- Animal Disease Management and Epidemiology
- Liver physiology and pathology
- T-cell and Retrovirus Studies
- Fibroblast Growth Factor Research
- Vector-Borne Animal Diseases
- Lung Cancer Research Studies
- Medical Imaging and Pathology Studies
- Neurofibromatosis and Schwannoma Cases
- Peroxisome Proliferator-Activated Receptors
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Cellular transport and secretion
- thermodynamics and calorimetric analyses
- Lung Cancer Treatments and Mutations
University of Kansas Medical Center
2008-2023
Stowers Institute for Medical Research
2021-2022
The University of Kansas Cancer Center
2008-2009
University of Kansas
2009
The University of Texas Southwestern Medical Center
2003-2004
The 90-kDa heat shock protein (Hsp90) assists in the proper folding of numerous mutated or overexpressed signal transduction proteins that are involved cancer. Consequently, there is considerable interest developing chemotherapeutic drugs specifically disrupt function Hsp90. Here, we investigated extent to which a novel novobiocin-derived C-terminal Hsp90 inhibitor, designated KU135, induced antiproliferative effects Jurkat T-lymphocytes. results indicated KU135 bound directly Hsp90, caused...
Background Appropriate responses to damaged DNA are indispensible for preserving genome stability and preventing cancer. Tumor viruses often target repair machinery achieve transformation. The Human T-cell leukemia virus type I (HTLV-I) is the only known transforming human retrovirus etiological agent of Adult Leukemia (ATLL). Although HTLV-I-transformed leukemic cells have numerous genetic lesions, precise role viral tax gene in this process not fully understood. Results Our results show a...
Mitochondrial outer membrane permeabilization and the release of intermembrane space proteins, such as cytochrome c, are early events during intrinsic (mitochondria-mediated) apoptotic signaling. Although this process is generally accepted to require activation Bak or Bax, underlying mechanism responsible for their true apoptosis not well understood. In current study, we investigated molecular requirements necessary using distinct clones Bax-deficient Jurkat T-lymphocytes in which pathway...
The extent to which the BH3-only protein Bid is important for intrinsic (mitochondria-mediated) apoptotic cell death induced by genotoxic stress remains controversial. In present study, we examine this issue using a panel of gene-manipulated Bax-deficient Jurkat T-lymphocytes. Cells stably depleted were far less sensitive than control-transfected cells etoposide-induced apoptosis. particular, drug-induced Bak activation, cytochrome c release, loss mitochondrial membrane potential, and...
Exposure of cells to hyperthermia is known induce apoptosis, although the underlying mechanisms are only partially understood. Here, we examine molecular requirements necessary for heat-induced apoptosis using genetically modified Jurkat T-lymphocytes. Cells stably overexpressing Bcl-2/Bcl-xL or depleted Apaf-1 were completely resistant implicating involvement mitochondria-mediated pathway. Pretreatment wild-type with cell-permeable biotinylated general caspase inhibitor b-VAD-fmk...
The yeast Saccharomyces cerevisiae contains two known phosphoinositide 4-kinases (PI 4-kinases), which are encoded by PIK1 and STT4; both essential. Pik1p is important for exocytic transport from the Golgi, whereas Stt4p plays a role in cell-wall integrity cytoskeletal rearrangements. In present study, we report that cells have third PI 4-kinase activity LSB6, protein identified previously two-hybrid screen as interacting with LAS17p. Although closely related members of Type III class...
Activation of executioner caspases during receptor-mediated apoptosis in type II cells requires the engagement mitochondrial apoptotic pathway. Although it is well established that recruitment mitochondria this context involves cleavage Bid to truncated (tBid), precise post-mitochondrial signaling responsible for caspase activation controversial. Here, we used distinct clones Jurkat T-lymphocytes which pathway had been inhibited investigate molecular requirements necessary Fas-induced...
Several peroxisomal proteins have two nonoverlapping targeting signals. These signals been termed "redundant" because can still occur with only one signal. We now report that separate motifs within both Pmp47 and Pex8 provide complementary function. is an ATP translocator contains six transmembrane domains (TMDs). had previously shown the TMD2 region (termed TMD2R, consisting of a short adjacent segment cytosolic loop) was required for to proliferated peroxisomes in Saccharomyces cerevisiae....
The promoter of the telomerase catalytic subunit (TERT) is subject to tight regulation and remains repressed in somatic cells ensure their limited life span prevent tumor initiation. Here we report that hTERT strongly by p53 related family members p63 p73. We found p53-mediated repression was different human mouse occurred through p53-dependent transcription inhibition c-Myc or E-box/E2F pathways, respectively. Although p63TAα-mediated SP1, p63TAy-mediated E2F signaling. Finally, p73α-...
Abstract Background The management of ultracentral thoracic tumors with ablative dose radiotherapy remains challenging given proximity to critical central structures. We report patient outcomes, toxicity, and dosimetry for ultracentrally located hypofractionated stereotactic body (hfSBRT). Methods Seventy-eight individuals (50 initial radiotherapy, 28 re-irradiation) undergoing 10 fraction hfSBRT treated between 2009 2020 at a single institution were retrospectively reviewed. Overall...
Abstract The inner nuclear membrane (INM) proteome regulates gene expression, chromatin organization, and transport; however, it is poorly understood how changes in INM protein composition contribute to developmentally regulated processes, such as gametogenesis. We conducted a screen determine the differs between mitotic cells gametes. In addition, we used strategy that allowed us if spores synthesize their proteins de novo, rather than inheriting from parental cell. This split-GFP...
Abstract Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with a 50% rate of local failure current standard care. We recently reported that patient-derived tumor associated fibroblasts (TAF) facilitate HNSCC proliferation metastasis to the cervical lymph node lung mice. Although paracrine molecular interactions between TAFs have not been fully described, we demonstrated (and HNSCC) secrete hepatocyte growth factor (HGF), ligand for c-Met receptor on cells. Further,...
Abstract Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC), which affects 50,000 new patients annually in the United States, is associated with less than 50% 5-year survival. HNSCC tumors display increased glycolysis, even presence of oxygen. Consequently, there an increase lactic acid (LA) production. However, effect tumor microenvironment mechanisms whereby survive highly acidic conditions remain unknown. consist up to 80% tumor-associated fibroblasts (TAFs). We...
Abstract Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy affecting 40,000 cases in the USA annually. Despite therapies HNSCC associated with less than a 50% 5-year survival rate. Limited treatment options high morbidity necessitate development of new treatments. tumors frequently consist up to 80% tumor-associated fibroblasts (TAFs). We reported that tumor (TAFs) facilitate progression. However, molecular mechanisms TAF-mediated growth metastasis remain unknown....
Abstract Introduction: This study was aimed to evaluate the outcomes of patients with large (>2 cm in great diameter) vestibular schwannomas (VSs) treated hypofractionated stereotactic radiotherapy (HFSRT) compared small (<2 cm) ones and impact debulking surgery prior radiation for VSs. Methods: Fifty-nine VSs HFSRT (25 Gy 5 fractions) were evaluated by tumour size surgical status. Patients divided based on size: ( n = 42) 17). The group further into groups pre-treatment 8) no 9)....
Abstract The inner nuclear membrane (INM) proteome regulates gene expression, chromatin organization, and transport, however, it is poorly understood how changes in INM protein composition contribute to developmentally regulated processes, such as gametogenesis. Using a split-GFP complementation system, we compared the distribution of all C-terminally tagged transmembrane proteins Saccharomyces cerevisiae gametes that mitotic cells. Gametes contain distinct needed complete gamete formation,...