A5013444827- Protein Degradation and Inhibitors
- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Neurofibromatosis and Schwannoma Cases
- Autophagy in Disease and Therapy
- Cell death mechanisms and regulation
- Neuroblastoma Research and Treatments
- Asthma and respiratory diseases
- Health and Medical Research Impacts
- Viral gastroenteritis research and epidemiology
- Cardiac Arrest and Resuscitation
- Disaster Response and Management
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- Toxin Mechanisms and Immunotoxins
- Dysphagia Assessment and Management
- Anatomy and Medical Technology
- Neuroscience of respiration and sleep
- Glioma Diagnosis and Treatment
- Respiratory viral infections research
- Sirtuins and Resveratrol in Medicine
- Innovations in Medical Education
- Virus-based gene therapy research
- Family and Patient Care in Intensive Care Units
- Respiratory and Cough-Related Research
University of Alabama at Birmingham
2013-2022
St. Vincent's Birmingham
2013
Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants. In tissue samples NEC, we identified numerous macrophages and a few neutrophils but not many lymphocytes. We hypothesized that these pathoanatomic characteristics NEC represent common injury response the gastrointestinal tract to variety insults at specific stage gut development. To evaluate developmental changes in mucosal response, used trinitrobenzene sulfonic acid (TNBS)-induced inflammation as...
The mechanisms by which cigarette smoking impairs airway mucus clearance are not well understood. We recently established a ferret model of smoke-induced chronic obstructive pulmonary disease (COPD) exhibiting bronchitis. investigated the effects smoke on mucociliary transport (MCT). Adult ferrets were exposed to for 6 months, with in vivo measured technetium-labelled DTPA retention. Excised tracheae imaged micro-optical coherence tomography. Mucus changes primary human epithelial cells and...
Tamoxifen is widely used to treat estrogen receptor-positive breast cancer. Recent findings that tamoxifen and its derivative 4-hydroxytamoxifen (OHT) can exert receptor-independent cytotoxic effects have prompted the initiation of clinical trials evaluate use in receptor-negative malignancies. For example, OHT malignant peripheral nerve sheath tumors (MPNST) where not involved. In this study, we gained insights into by studying how it kills MPNST cells. Although caspases were activated...
Glioblastomas (GBMs) are the most common and aggressive primary human malignant brain tumors. 4-Hydroxy tamoxifen (OHT) is an active metabolite of (TMX) prodrug a well-established estrogen receptor (ER) estrogen-related antagonist. A recent study from our laboratory demonstrated that OHT induced ER-independent peripheral nerve sheath tumor (MPNST) cell death by autophagic degradation prosurvival protein Kirsten rat sarcoma viral oncogene homolog. Because both MPNST GBM glial in origin, we...
Rationale The majority of chronic obstructive pulmonary disease (COPD) patients have bronchitis, for which specific therapies are unavailable. Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is observed in but has not been proven a controlled animal model with airway disease. Furthermore, the potential CFTR as therapeutic target tested vivo, given limitations to rodent models COPD. Ferrets exhibit fibrosis-related lung pathology when absent and COPD bronchitis...
Faculty qualified to teach in the anatomical sciences are growing scarce just as need for trained anatomists is greater than ever. Enrollments surging anticipation of a large physician shortfall; meanwhile, many reaching retirement age. Who will fill teaching gap? This study assessed trends doctorates awarded Anatomy and related fields within United States (US) since 1969 evaluated modern graduate education sciences. Data were compiled from National Science Foundation Survey Earned...
DNA methylation is a major epigenetic event that affects not only cellular gene expression but also has the potential to influence bacterial and viral in their host-dependent functions. Adeno-associated virus (AAV) genome contains high degree of CpG sequences capable its terminal repeat sequences, which are sole elements retained AAV-based vectors used therapy. The present study determined status host cell on wild type (wt) AAV integration recombinant (r) transgene HeLa cells. Results...
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived sarcomas and the leading cause of mortality in patients with neurofibromatosis type 1 (NF1). Current treatment modalities have been largely ineffective, resulting a high rate MPNST recurrence poor five-year patient survival. This necessitates exploration alternative chemotherapeutic options for patients. study sought to assess cytotoxic effect BH3-mimetic AT101 [(-)-gossypol] on cells vitro identify key...
Malignant peripheral nerve sheath tumors (MPNSTs) are rapidly progressive Schwann cell neoplasms. The erbB family of membrane tyrosine kinases has been implicated in MPNST mitogenesis and invasion and, thus, is a potential therapeutic target. However, kinase inhibitors (TKIs) used alone have limited tumoricidal activity. Manipulating the autophagy lysosomal pathway cells treated with cytostatic agents can promote apoptotic death some cases. goal this study was to establish mechanistic basis...
Limited success achieved in translating basic science discoveries into clinical applications for chronic airway diseases is attributed to differences respiratory anatomy and physiology, poor approximation of pathologic processes, lack correlative endpoints between humans laboratory animal models. Here, we discuss advantages using ferrets (Mustela putorus furo) as a model improved understanding human physiology demonstrate assays quantifying epithelial ion transport vivo ex vivo, establish...
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, Schwann cell-derived neoplasms of the nervous system that have recently been shown to possess an autocrine CXCL12/CXCR4 signaling loop promotes tumor cell proliferation and survival. Importantly, axis is driven by availability CXCL12 ligand rather than CXCR4 receptor levels alone. Therefore, pharmacological reduction expression could be a potential chemotherapeutic target for patients with MPNSTs or other pathologies wherein...
Airway dehydration causes mucus stasis and bacterial overgrowth in cystic fibrosis (CF), resulting recurrent respiratory infections exacerbations. Strategies to rehydrate airway including inhibition of the epithelial sodium channel (ENaC) have potential improve mucosal defense by enhancing mucociliary clearance (MCC) reducing risk progressive decline lung function. In current work, we evaluated effects AZD5634, an ENaC inhibitor that shows extended retention safety profile as compared with...
Therapy-induced autophagy is recognized as a critical determinant of treatment outcome in cancer patients, primarily factor underlying drug resistance. However, recent investigations point toward context-dependent, death-inducing role for autophagy, the mechanism which remains largely unknown. Our study provides evidence that can directly mediate cell killing multiple tumor types by facilitating degradation KRAS/K-Ras, key survival protein. These findings have broad implications strategies...
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, Schwann cell‐derived neoplasms of the nervous system. MPNSTs have recently been shown to possess an autocrine CXCL12/CXCR4 signaling loop that promotes tumor cell proliferation and survival. Importantly, axis is driven by availability CXCL12 ligand rather than CXCR4 receptor levels. Accordingly, pharmacological reduction expression and/or secretion could be a potential chemotherapeutic option for patients with or other...
Tamoxifen (TMX) is widely used as a chemotherapeutic agent in the treatment of estrogen receptor (ER)‐positive breast cancer. Recent studies have demonstrated that TMX inhibits growth malignant peripheral nerve sheath tumors (MPNSTs) through an ER‐independent mechanism associated with induction autophagy. We hypothesize could induce autophagic cell death glioblastoma (GBM), most common and aggressive astrocytic glioma. In established human GBM line xenografts, caused concentration‐dependent...
Abstract Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell-derived sarcomas. MPNSTs the leading cause of mortality in patients with neurofibromatosis type 1 (NF1), an autosomal dominant genetic disease. Current treatment modalities have been ineffective resulting high recurrence (40–68%) and poor five year survival rate between 16–52% these tumors. This necessitates need for novel therapeutic options. The anti-apoptotic members Bcl-2 family reported to be...
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell‐derived sarcomas and a leading cause of mortality in neurofibromatosis type 1 (NF1) patients. Current treatment modalities have been ineffective resulting high rate recurrence poor five year survival, which necessitates the exploration novel therapeutic agents. AT101, BH3 mimetic, has shown to induce cell death several cancers is phase II clinical trials. The objective this study was investigate molecular...