A5062506908- Cell death mechanisms and regulation
- Ion channel regulation and function
- Blood groups and transfusion
- Cancer-related Molecular Pathways
- COVID-19 Clinical Research Studies
- Mitochondrial Function and Pathology
- SARS-CoV-2 and COVID-19 Research
- Neuroscience and Neuropharmacology Research
- Hemoglobinopathies and Related Disorders
- Blood transfusion and management
- Erythrocyte Function and Pathophysiology
- Sperm and Testicular Function
- Vitamin C and Antioxidants Research
- Immune Response and Inflammation
- Blood donation and transfusion practices
- Cellular transport and secretion
- Neuroscience and Neural Engineering
- Cardiac electrophysiology and arrhythmias
- Autophagy in Disease and Therapy
- DNA Repair Mechanisms
- Iron Metabolism and Disorders
- Molecular Biology Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Reproductive Biology and Fertility
- RNA Interference and Gene Delivery
University of Iowa Health Care
2021-2024
University of Iowa
2013-2024
University of Iowa Hospitals and Clinics
2015-2022
Iowa City VA Health Care System
2015
National Institute of Diabetes and Digestive and Kidney Diseases
2010
University of Iowa Holden Comprehensive Cancer Center
2010
National Institute of Pathology
2005
Merck & Co., Inc., Rahway, NJ, USA (United States)
2002
Washington University in St. Louis
1996-1999
Laboratoire de Biochimie
1999
BAX, a heterodimeric partner of BCL2, counters BCL2 and promotes apoptosis in gain-of-function experiments. A Bax knockout mouse was generated that proved viable but displayed lineage-specific aberrations cell death. Thymocytes B cells this hyperplasia, Bax- deficient ovaries contained unusual atretic follicles with excess granulosa cells. In contrast, -deficient males were infertile as result disordered seminiferous tubules an accumulation atypical premeiotic germ cells, no mature haploid...
The ongoing coronavirus disease 2019 (COVID-19) pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first few months of pandemic, many features COVID-19 pathogenesis remain to be determined. For example, anosmia a common presentation, patients show no or only minor respiratory symptoms1. Studies animals infected experimentally severe acute syndrome 2 (SARS-CoV-2), cause COVID-19, provide opportunities study aspects that are not easily...
Dissociated cerebellar granule cells maintained in medium containing 25 mM potassium undergo an apoptotic death when switched to with 5 potassium. Granule from mice which Bax, a proapoptotic Bcl-2 family member, had been deleted, did not apoptosis potassium, yet excitotoxic cell response stimulation 30 or 100 μM NMDA. Within 2 h after switching K+, both wild-type and Bax-deficient decreased glucose uptake <20% of control. Protein synthesis also rapidly 50% control within 12 Both Bax...
The death of cranial and spinal motoneurons (MNs) is believed to be an essential component the pathogenesis amyotrophic lateral sclerosis (ALS). We tested this hypothesis by crossing Bax-deficient mice with expressing mutant superoxide dismutase 1 (SOD1), a transgenic model familial ALS. Although Bax deletion failed prevent neuromuscular denervation mitochondrial vacuolization, MNs were completely rescued from SOD1-mediated death. However, deficiency extended lifespan delayed onset motor...
Pharmacologic concentrations of ascorbate may be effective in cancer therapeutics. We hypothesized that achievable with i.v. dosing would cytotoxic pancreatic for which the 5-year survival is <3%.Pancreatic cell lines were treated (0, 5, or 10 mmol/L) 1 hour, then viability and clonogenic determined. Pancreatic tumor cells delivered s.c. into flank region nude mice allowed to grow at time they randomized receive either (4 g/kg) osmotically equivalent saline (1 mol/L) i.p. 2 weeks.There was a...
Abstract Obesity is associated with an increased risk of developing breast cancer and also worse clinical prognosis. The mechanistic link between obesity progression remains unclear, there has been no development specific treatments to improve the outcome obese patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes progression. tumour microenvironment in context induces increase tumour-infiltrating myeloid cells activated turn...
Inactivation of p53-dependent apoptosis promotes oncogenic transformation, tumor development, and resistance to many cytotoxic anticancer agents. p53 can transcriptionally activate bax , a bcl-2 family member that apoptosis. To determine whether is required for apoptosis, the effects deficiency were examined in primary fibroblasts expressing E1A oncogene, setting where dependent on endogenous p53. We demonstrate function as an effector chemotherapy-induced contributes pathway suppress...
Abstract In sepsis there is extensive apoptosis of lymphocytes, which may be beneficial by down-regulating the accompanying inflammation. Alternatively, detrimental impairing host defense. We studied whether Bcl-2, a potent antiapoptotic protein, could prevent lymphocyte in clinically relevant model sepsis. Transgenic mice Bcl-2 was overexpressed T cells had complete protection against sepsis-induced thymus and spleen. Surprisingly, also decrease splenic B cell septic overexpressors compared...
The proapoptotic molecule BAX is required for death of sympathetic and motor neurons in the setting trophic factor deprivation. Furthermore, adult Bax−/− mice have more than do their wild-type counterparts. These findings raise possibility that regulates naturally occurring cell during development many neuronal populations. To test this idea, we assessed apoptosis using TUNEL labeling several well-studied neural systems embryonic early postnatal mice. Remarkably, virtually eliminated between...
The tumor suppressor gene p53 has been implicated in the loss of neuronal viability, but signaling events associated with p53-mediated cell death cortical and hippocampal neurons are not understood. Previous work shown that adenovirus-mediated delivery causes some features typical apoptosis. In present study we determined whether p53-initiated changes viability were dependent on members Bcl-2 family regulators. Primary cultures derived from animals containing Bax (+/+ +/-) or those deficient...
In the sarcoplasmic reticulum membrane of skeletal muscle, ryanodine receptor forms an aqueous pore identified as calcium-release pathway that operates during excitation-contraction coupling. The purified channel has now been shown to have four properties usually associated with gap junction channels: (i) a large nonspecific voltage-dependent conductance consisting several open states; (ii) inhibition probability by low p H; (iii) calcium; and (iv) sensitivity blockade heptanol octanol but...
The high affinity ryanodine receptor of the Ca2+ release channel from junctional sarcoplasmic reticulum rabbit skeletal muscle has been identified and characterized using monoclonal antibodies.Anti-ryanodine antibody XA7 specifically immunoprecipitated [SH]ryanodine-labeled digitonin-solubilized triads in a dose-dependent manner.['HIRyanodine binding to unlabeled was specific, Ca2+-dependent, stimulated by millimolar ATP, inhibited micromolar ruthenium red.Indirect immunoperoxidase staining...
Bax is a multidomain, proapoptotic member of the Bcl-2 family that required for normal spermatogenesis in mice. Despite its function, previous results found Bax-deficient mature male mice demonstrate increased cell death and dramatic testicular atrophy. The present study examined role during development testis to determine whether could be explained by decreased apoptosis earlier development. Consistent with this hypothesis, atrophy preceded weight hypercellular tubules immature TUNEL...