A5103073940- Bacillus and Francisella bacterial research
- Viral Infections and Vectors
- Poxvirus research and outbreaks
- Cancer Cells and Metastasis
- Erythrocyte Function and Pathophysiology
- Mosquito-borne diseases and control
- SARS-CoV-2 and COVID-19 Research
- Herpesvirus Infections and Treatments
- COVID-19 Clinical Research Studies
- Bacteriophages and microbial interactions
- Viral Infections and Outbreaks Research
- Tissue Engineering and Regenerative Medicine
- Yersinia bacterium, plague, ectoparasites research
- Disaster Response and Management
- Hip and Femur Fractures
- Helicobacter pylori-related gastroenterology studies
- Genetic factors in colorectal cancer
- Neonatal Respiratory Health Research
- Cellular transport and secretion
- Cellular Mechanics and Interactions
- Vector-Borne Animal Diseases
- Neonatal and Maternal Infections
- Immunodeficiency and Autoimmune Disorders
- Heat shock proteins research
- Plant Virus Research Studies
United States Army Medical Research Institute of Infectious Diseases
2019-2024
Vanderbilt University
2008-2020
Pennsylvania State University
1999-2011
Sir Charles Gairdner Hospital
2001
Autophagy plays a critical role in multiple aspects of the immune system, including development and function T lymphocytes. In mammalian cells, class III PI3K vacuolar protein sorting (Vps)34 is thought to play autophagy. However, recent studies have cast doubt on Vps34 autophagy, at least certain cell types. To study effects autophagy lymphocytes, we generated mice that selectively lack lineage. ablation cells caused profound defects autophagic flux, resulting accumulation cellular...
The incorporation of the envelope glycoprotein complex (Env) onto developing particle is a crucial step in HIV-1 lifecycle. long cytoplasmic tail (CT) Env required for HIV particles T cells and macrophages. Here we identify Rab11a-FIP1C/RCP protein as an essential cofactor relevant human cells. Depletion FIP1C reduced tail-dependent manner, was rescued by replenishment FIP1C. redistributed out endosomal recycling to plasma membrane wild type but not CT-truncated Env. Rab14 incorporation,...
Abstract Approximately 30% of triple-negative breast cancers (TNBC) harbor molecular alterations in PI3K/mTOR signaling, but therapeutic inhibition this pathway has not been effective. We hypothesized that intrinsic resistance to TORC1/2 is driven by cancer stem cell (CSC)-like populations could be targeted enhance the antitumor action these drugs. Therefore, we investigated mechanisms which inhibitors affect stem-like properties TNBC cells. Treatment established lines with a inhibitor or...
An antibody targeting the CCHFV GP38 molecule protects adult mice against lethal infection in a severe disease model.
Animal models recapitulating human COVID-19 disease, especially severe are urgently needed to understand pathogenesis and evaluate candidate vaccines therapeutics. Here, we develop novel severe-disease animal for involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or
Abstract Background : People who return to living in the community after a hip fracture are considered have best outcome. However, their quality of life (QOL) and its relationship with function over longer term not been fully assessed. Aims This case control study dwelling subjects six 12 months post aims investigate QOL functional independence. Method The Short Form‐36 (SF‐36) was utilised measure QOL. Modified Barthel Index (MBI), Frenchay Activities Daily Living (FAI), Timed `Up & Go'...
Genesis of myofibroblasts is obligatory for the development pathology in many adult lung diseases. Adult tissue contains a population perivascular ABCG2(pos) mesenchymal stem cells (MSC) that are precursors and distinct from NG2 pericytes. We hypothesized these MSC participate deleterious remodeling associated with pulmonary fibrosis (PF) hypertension (PH). To test this hypothesis, resident were quantified samples control subjects PF patients. cell numbers decreased human interstitial...
Inactivating mutations in MYO5B cause severe neonatal diarrhea Microvillus Inclusion Disease. Loss of active causes the formation pathognomonic inclusions and aberrations brush border enzymes.
Effective therapeutics have been developed against acute Ebola virus disease (EVD) in both humans and experimentally infected nonhuman primates. However, the risk of viral persistence associated recrudescence survivors receiving these remains unclear. In contrast to rhesus macaques that survived (EBOV) exposure absence treatment, we discovered EBOV, despite being cleared from all other organs, persisted brain ventricular system macaque had received monoclonal antibody (mAb) treatment....
Chemotherapy against human African trypanosomiasis relies on four drugs that cause frequent and occasionally severe side‐effects. Because is a disease of poor people in Africa, the traditional market‐driven pathways to drug development are not available. One potentially rapid cost‐effective approach identifying developing new trypanocidal would be high throughput‐screening existing already approved for other uses, as well clinical candidates late development. We have developed an...
Alveolar type II (AT2) epithelial cells are uniquely specialized to produce surfactant in the lung and act as progenitor process of repair after injury. AT2 cell injury has been implicated several diseases, including idiopathic pulmonary fibrosis bronchopulmonary dysplasia. The inability maintain primary culture a significant barrier investigation biology. We have addressed this knowledge gap by developing three-dimensional (3D) organotypic coculture using human fetal fibroblasts. Grown on...
The rapid emergence of SARS-CoV-2 has created a global health emergency. While most human disease is mild, some people develop severe, life-threatening disease.
Human monkeypox (mpox) has recently become a global public health emergency; however, assays that detect mpox infection are not widely available, largely due to cross-reactivity within the Orthopoxvirus genus. Immunoassay development was confined researchers who focus on biothreats and endemic areas (Central West Africa) until 2022 outbreak. As noted in COVID-19 pandemic, antigen detection assays, integrated with molecular necessary help curb spread of disease. Antigen-detecting immunoassays...
Abstract Dysplasia is considered a key transition state between pre-cancer and cancer in gastric carcinogenesis. However, the cellular or phenotypic heterogeneity mechanisms of dysplasia progression have not been elucidated. We established metaplastic dysplastic organoid lines, derived from Mist1-Kras(G12D) mouse stomach corpus studied distinct behaviors characteristics organoids. also examined functional roles for Kras activation using Selumetinib, MEK inhibitor, which downstream mediator...
Perinatal infection with Streptococcus agalactiae, or Group B (GBS), is associated preterm birth, neonatal sepsis, and stillbirth. Here, we study the interactions of GBS macrophages, essential sentinel immune cells that defend gravid reproductive tract. Transcriptional analyses GBS-macrophage co-cultures reveal enhanced expression a gene encoding putative metal resistance determinant, cadD. Deletion cadD reduces survival in efflux, to toxicity. In mouse model ascending during pregnancy,...
Poxviruses exist as multiple infectious morphogenic forms commonly simplified mature virions (MV) and extracellular (EV). The roles of subtypes related to disease transmission are enigmatic EVs can both cell associated (CEV) or released particles (rCEV) each with potentially unique biochemical properties impacting stability infectivity. In vitro analysis prototypical poxviruses is utilized infer larger conclusions about the in vivo function all EV-like particles. Here we present data...
Eastern equine encephalitis virus (EEEV) is mosquito-borne that produces fatal in humans. We recently conducted a first of its kind study to investigate EEEV clinical disease course following aerosol challenge cynomolgus macaque model utilizing the state-of-the-art telemetry measure critical physiological parameters. Here, we report results comprehensive pathology NHP tissues collected at euthanasia gain insights into pathogenesis. Viral RNA and proteins as well microscopic lesions were...
The origin of epithelial cell polarity during development is a fundamental problem in biology. Central to this process the establishment asymmetric membrane domains that will ultimately form apical and basolateral surfaces. spectrin-based skeleton has long been thought participate generation asymmetry. Drosophila melanogaster contains two known (beta)-spectrin isoforms: conventional chain, novel isoform (beta)(Heavy)-spectrin. These proteins are restricted domains, respectively. To assay for...
The role of the cytoskeleton in protein trafficking is still being defined. Here, we describe a relationship between small Ca2+-dependent membrane-binding Annexin B9 (AnxB9), apical βHeavy-spectrin (βH) and multivesicular body (MVB) Drosophila. AnxB9 binds to subset βH spliceoforms, loss results an increase basolateral its appearance on cytoplasmic vesicles that overlap with MVB markers Hrs, Vps16 EPS15. Similar colocalizations are seen when βH-positive endosomes generated either by...
Type IV pili are involved in adhesion, twitching motility, aggregation, biofilm formation and virulence a variety of Gram-negative bacteria. Burkholderia pseudomallei, the causative agent melioidosis Tier 1 biological select agent, is bacterium with eight type pili-associated loci (TFP1 to TFP8). Most have not been fully characterized. In this study, we investigated BPSS2185 , an uncharacterized TFP8 gene that encodes IVB pilus protein subunit. Using genetic deletion complementation analysis...
Current models of cell polarity invoke asymmetric cues that reorganize the secretory apparatus to induce polarized protein delivery. An important step in this process is stabilization composition each membrane domain. The spectrin-based skeleton thought contribute such by increasing half-life many proteins at surface. Genetic evidence consistent with a negative role for Drosophila βHeavy-spectrin endocytosis, but inhibitory mechanism has not been elucidated. Here, we investigated binding...
Abstract Background and Aims: PTK6 is an intracellular src‐related tyrosine kinase that regulates differentiation in the intestine, where knockout animals have increased proliferative activity growth characteristics. To explore phenotype further we attempted to establish epithelial cell lines from intestinal mucosa. Method: We mated Ptk 6 null mice with a tsSV40 large T transgenic mouse (Immortomouse) obtain carrying SV40 gene. Intestinal tissues these were cultured. Results: established...
Directed delivery of EGF receptor (EGFR) ligands to the apical or basolateral surface is a crucial regulatory step in initiation EGFR signaling polarized epithelial cells. Herein, we show that ligand, betacellulin (BTC), preferentially sorted MDCK By sequential truncations and site-directed mutagenesis within BTC cytoplasmic domain, combined with selective cell-surface biotinylation immunofluorescence, have uncovered monoleucine-based sorting motif (EEXXXL:E156EMETL). Disruption this led...