A5037212349- Fish Ecology and Management Studies
- Aquaculture Nutrition and Growth
- 3D Printing in Biomedical Research
- Genetic Associations and Epidemiology
- Cancer Cells and Metastasis
- Physiological and biochemical adaptations
- Reproductive biology and impacts on aquatic species
- Wildlife Ecology and Conservation
- Aquaculture disease management and microbiota
- Estrogen and related hormone effects
- Water Quality and Resources Studies
- Trypanosoma species research and implications
- Marine and fisheries research
- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- Lipid metabolism and biosynthesis
- Histone Deacetylase Inhibitors Research
- Research on Leishmaniasis Studies
- Genetic and phenotypic traits in livestock
- Protein Kinase Regulation and GTPase Signaling
- Retinal Diseases and Treatments
- Virus-based gene therapy research
- Liver physiology and pathology
- Ion Channels and Receptors
University of Pittsburgh
2013-2024
AstraZeneca (United Kingdom)
2019-2022
AbbVie (United States)
2020
Fisheries and Oceans Canada
2016
University of British Columbia
2011-2016
Discovery Institute
2009-2011
Confederated Tribes of Warm Springs
2000-2010
Michigan State University
2005-2010
Michigan Department of Natural Resources
2005-2008
Oregon Department of Fish and Wildlife
2000-2003
Abstract Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses 141 species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10 −8 ), 10 which associate risk including five new loci- COL5A1 , GLTPD2 SPTLC3 MBOAT7 GALNT16 (false...
The cultural and ecological values of Pacific lamprey (Lampetra tridentata) have not been understood by Euro-Americans thus their great decline has almost gone unnoticed except Native Americans, who elevated the issue initiated research to restore its populations, at least in Columbia Basin. They regard as a highly valued resource result ksuyas (lamprey) become one icons. Ksuyas are harvested this day subsistence food various tribes along coast regarded for value. Interestingly, our review...
Abstract Unlike most anadromous fishes that have evolved strict homing behaviour, P acific lamprey ( E ntosphenus tridentatus ) seem to lack philopatry as evidenced by minimal population structure across the species range. Yet unexplained findings of within‐region genetic heterogeneity coupled with morphological and behavioural diversity described for suggest adaptive variation underlying fitness traits may be responsible. We employed restriction site–associated DNA sequencing genotype 4439...
Abstract Polygenic risk scores (PRS) for breast cancer have potential to improve prediction, but there is limited information on their utility in various clinical situations. Here we show that among 122,978 women the FinnGen study with 8401 cases, PRS modifies of two high-impact frameshift variants. Similarly, after diagnosis, individuals elevated an developing contralateral cancer, and can considerably assessment female first-degree relatives. In more detail, c.1592delT variant PALB2...
Corticosteroid hormones are critical for controlling metabolism, hydromineral balance, and the stress response in vertebrates. Although corticosteroid have been well characterized most vertebrate groups, identity of earliest hormone has remained elusive. Here we provide evidence that 11-deoxycortisol is lamprey, a member agnathans evolved more than 500 million years ago. We used RIA, HPLC, mass spectrometry analysis to determine active present lamprey plasma. also an receptor extracted from...
Despite significant investments in cancer research and drug discovery/development, the rate of new approval is ≤5% most cases metastatic remain incurable. Ninety-five percent drugs fail clinical development because a lack therapeutic efficacy and/or unacceptable toxicity. One major factors responsible for low success anticancer failure preclinical models to adequately recapitulate complexity heterogeneity human cancer. For throughput capacity reasons, high-throughput screening growth...
Summary 1. Spatial patterns in channel morphology and substratum composition at small (1–10 metres) large scales kilometres) were analysed to determine the influence of habitat heterogeneity on distribution abundance larval lamprey. 2. We used a nested sampling design multiple logistic regression evaluate spatial Pacific lamprey, Lampetra tridentata , 30 sites (each composed twelve 1‐m 2 quadrat samples) distributed throughout 55‐km section Middle Fork John Day River, OR, U.SA. Statistical...
Patients with clinical manifestations of leishmaniasis, including cutaneous have limited treatment options, and existing therapies frequently significant untoward liabilities. Rapid expansion in the diversity available leishmanicidal chemotypes is initial step finding alternative efficacious treatments. To this end, we combined a low-stringency Leishmania major promastigote growth inhibition assay structural computational filtering algorithm. After rigorous validation process, interrogated...
Cutaneous leishmaniasis remains ignored in therapeutic drug discovery programs worldwide. This is mainly because cutaneous frequently a disease of impoverished populations countries where funds are limited for research and patient care. However, the health burden individuals endemic areas mandates readily available, effective, safe treatments. Of existing therapeutics, many growth inhibitory to Leishmania parasites, potentially creating dormant parasite reservoirs that can be activated when...
Glucocorticoids (GCs) are produced by the adrenal glands and circulate in blood to coordinate organismal physiology. In addition, different tissues may independently regulate their local GC levels via synthesis. Here, we find that mouse, endogenous GCs show tissue-specific developmental patterns, rather than mirroring blood. Using solid-phase extraction, HPLC, specific immunoassays, quantified steroids found of female male mice, (1) can be much higher systemic levels, (2) follow age-related...
Studies have demonstrated ways in which climate-related shifts the distributions and relative abundances of marine species are expected to alter dynamics catch potential global fisheries. While these studies assess impacts on large-scale commercial fisheries, few efforts been made quantitatively project small-scale subsistence fisheries that economically, socially culturally important many coastal communities. This study uses a dynamic bioclimate envelope model scenarios changes abundance,...
In solid tumors like head and neck cancer (HNC), chronic acute hypoxia have serious adverse clinical consequences including poorer overall patient prognosis, enhanced metastasis, increased genomic instability, resistance to radiation-, chemo-, or immuno-therapies. However, cells in the two-dimensional monolayer cultures typically used for drug discovery experience 20%-21% O2 levels (normoxic) which are 4-fold higher than normal tissues ≥10-fold hypoxic regions of tumors. The oxygen...
Background The parasitic protozoan Trypanosoma brucei utilizes glycolysis exclusively for ATP production during infection of the mammalian host. first step in this metabolic pathway is mediated by hexokinase (TbHK), an enzyme essential to parasite that transfers γ-phospho a hexose. Here we describe identification and confirmation novel small molecule inhibitors bacterially expressed TbHK1, one two TbHKs T. brucei, using high throughput screening assay. Methodology/Principal Findings...
Pacific lamprey, Lampetra tridentata , has declined precipitously throughout their range in the Columbia River basin of North America. Tribal Nations and Federal State agencies are engaged efforts to restore these fish. Understanding whether lamprey emit detect migratory pheromones is particularly important for restoration efforts. Using behavioural assays, we demonstrated that adult attracted odors emanating from larval conspecifics. We then identified putative released by lamprey. Chemical...
Multicellular tumor spheroid (MCTS) cultures represent more physiologically relevant in vitro cell models that recapitulate the microenvironments and cell–cell or cell–extracellular matrix interactions which occur solid tumors. We characterized morphologies, viability, growth behaviors of MCTSs produced by 11 different head neck squamous carcinoma (HNSCC) lines seeded into cultured ultra-low attachment microtiter plates (ULA-plates) over extended periods time. HNSCC MCTS developed...
<h3>Importance</h3> Randomized clinical trials demonstrate no benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in unselected patients with head and neck squamous cell carcinoma (HNSCC). However, a patient stage IVA HNSCC received 13 days of neoadjuvant erlotinib experienced near-complete histologic response. <h3>Objective</h3> To determine mechanism exceptional response to therapy HNSCC. <h3>Design, Setting, Participants</h3> Single locally advanced who...
Abstract Background and Purpose We extend the characterization of TRPM8 antagonist VBJ103 with tests selectivity, specificity distribution, therapeutic efficacy systemic administration against oxaliplatin‐induced cold hyperalgesia impact on core body temperature (CBT). Experimental Approach Selectivity at human TRPA1 TRPV1 as well in vitro safety profiling was determined. Effects were evaluated a model hyperalgesia. Both peripheral centrally mediated effects CBT assessed radiotelemetry. Key...
High cancer drug development attrition rates have provoked considerable debate about whether the two-dimensional tumor growth inhibition high-throughput screening assays used in pre-clinical lead discovery adequately reflect solid complexity. We automated high-content image acquisition and analysis methods to compare fluorescent uptake, accumulation, distribution Cal33 FaDu head neck (HNC) monolayer multicellular spheroid (MCTS) models. Ellipticine, idarubicin, daunorubicin, doxorubicin were...
Acute kidney injury (AKI), a sudden loss of function, is common and serious condition for which there are no approved specific therapies. While multiple approaches to treat the underlying causes AKI, targets have been clinically validated. Here, we assessed series potent, selective competitive inhibitors histone deacetylase 8 (HDAC8), promising therapeutic target in an AKI setting. Using biochemical assays, zebrafish phenotypic human organoid show that HDAC8 can lead efficacy increasingly...