A5081118410- CRISPR and Genetic Engineering
- Neuroscience and Neuropharmacology Research
- Synthesis and Biological Evaluation
- Phenothiazines and Benzothiazines Synthesis and Activities
- Ubiquitin and proteasome pathways
- Viral Infectious Diseases and Gene Expression in Insects
- Cell Adhesion Molecules Research
- MicroRNA in disease regulation
- Inhalation and Respiratory Drug Delivery
- Adipose Tissue and Metabolism
- Genetic Syndromes and Imprinting
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- RNA modifications and cancer
- Colorectal Cancer Screening and Detection
- Musculoskeletal pain and rehabilitation
- Diabetes and associated disorders
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Occupational exposure and asthma
- HER2/EGFR in Cancer Research
- Primary Care and Health Outcomes
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cancer Cells and Metastasis
- Diabetes Management and Research
Medical College of Wisconsin
2024
Covance (United Kingdom)
2022
Eastern Virginia Medical School
2017
Genentech
2011-2015
East Carolina University
2005-2013
MSD (UK) Limited (United Kingdom)
2005-2007
Merck & Co., Inc., Rahway, NJ, USA (United States)
2005
Madigan Army Medical Center
1999
Wacker (United States)
1995-1997
Maebashi Institute of Technology
1995-1997
The basal-like subtype of breast cancer has an aggressive clinical behavior compared to that the luminal subtype. We identified microRNAs (miRNAs) miR-221 and miR-222 (miR-221/222) as subtype-specific miRNAs showed expression miR-221/222 decreased epithelial-specific genes increased mesenchymal-specific genes, cell migration invasion in a manner characteristic epithelial-to-mesenchymal transition (EMT). transcription factor FOSL1 (also known Fra-1), which is found cancers but not subtype,...
MicroRNAs miR-221 and miR-222 are associated with a clinically aggressive form of breast cancer promote epithelial-to-mesenchymal transition.
We examined hematopoietic protein kinase 1 (HPK1), whose reliance on scaffold versus functions for negative immune cell regulation is poorly understood and critical to its assessment as a viable drug target. identify kinase-dependent roles HPK1 in CD8 T cells that restrict their anti-viral anti-tumor responses by using kinase-dead (HPK1.kd) knockin mice. Loss of function enhanced receptor signaling cytokine secretion T-cell-intrinsic manner. In response chronic lymphocytic choriomeningitis...
Idiopathic pulmonary fibrosis is a progressive fibrotic disease characterized by excessive deposition of (myo)fibroblast produced collagen fibrils in alveolar areas the lung. Lysyl oxidases (LOXs) have been proposed to be central enzymes that catalyze cross-linking fibers. Here, we report that, while its expression increased lungs, genetic ablation LOXL2 only leads modest reduction pathological but not On other hand, loss another LOX family member, LOXL4, markedly disrupts and Furthermore,...
Peg10 (paternally expressed gene 10) is an imprinted that essential for placental development. It thought to derive from a Ty3-gyspy LTR (long terminal repeat) retrotransposon and retains Gag Pol-like domains. Here we show the domain of PEG10 can promote vesicle budding similar HIV p24 protein. Expressed in subset mouse endocrine organs addition placenta, was identified as substrate deubiquitinating enzyme USP9X. Consistent with having critical role development, PEG10-deficient trophoblast...
Fibroblast Growth Factor 21 (FGF21) is a potent stimulator of brown fat thermogenesis that improves insulin sensitivity, ameliorates hepatosteatosis, and induces weight loss by engaging the receptor complex comprised Receptor 1 (FGFR1) requisite coreceptor βKlotho. Previously, recombinant antibody proteins activate FGFR1/βKlotho were proposed to act as an FGF21-mimetic; however, in vivo action these engineered has not been well studied. We investigated mechanism which anti-FGFR1/βKlotho...
Abstract This study examines the historical and contemporary power structures in U.S. Parks Protected Areas (PPAs) proposes a framework for transitioning toward more equitable management practices that are centered on Indigenous leadership sovereignty. As an authorship team of non‐Indigenous scholars, we critique colonial infrastructure has maintained settler over lands waters by employing decolonial feminist methodologies adapting evaluation model to understand PPA paradigms along spectrum...
The identification of a series imidazo[1,2-b][1,2,4]triazines with high affinity and functional selectivity for the GABA(A) alpha3-containing receptor subtype is described, leading to clinical candidate, 11. Compound 11 shows good bioavailability half-life in preclinical species, it nonsedating anxiolytic both rat squirrel monkey behavioral models.
Five percent of family physicians offer colonoscopy services, either in the office or hospital, often rural areas that have no gastroenterologist. Two previous large series shown quality and safety performed by physicians. The purpose this study was to verify these findings an outpatient setting, as well obtain patient satisfaction data.Data were obtained from 731 colonoscopies between 1996 2001 a Virginia practice. These data included patients' age sex, indications for procedure, drug...
A simple and efficient strategy for Bacterial Artificial Chromosome (BAC) recombineering based on co-selection is described. We show that it possible to efficiently modify two positions of a BAC simultaneously by co-transformation single-stranded DNA oligo double-stranded selection cassette. The use reduces the manipulation needed make conditional knockout gene targeting vector only steps: single round modification followed retrieval step.
Proteolytic processing of procollagens is a central step during collagen fibril formation. Bone morphogenic protein 1 (BMP1) metalloprotease that plays an important role in the cleavage carboxy-terminal (COOH-terminal) propeptides from procollagens. Although removal required to generate mature fibrils, contribution BMP1 this proteolytic process and its action site remain be fully determined. In study, using postnatal lung fibroblasts as model system, we showed genetic ablation Bmp1 primary...
The need for a high degree of flexibility within compound screening is requirement throughout the drug discovery industry. demands made automation technology are becoming increasingly sophisticated as assay formats diversify and confidence in grows. To meet these high-performance flexibility, MSD with RTS Life Science have developed installed dual-robot arm system at our Terlings Park site to support early stage discovery. Plate transport on via two articulated robotic Staubli arms. has...
Abstract Bone morphogenetic protein 1 (BMP1) belongs to the astacin/BMP1/tolloid-like family of zinc metalloproteinases, which play a fundamental role in development and formation extracellular matrix (ECM). BMP1 mediates cleavage carboxyl terminal (C-term) propeptides from procollagens, crucial step fibrillar collagen fiber formation. Blocking by small molecule or antibody inhibitors has been linked anti-fibrotic activity preclinical models skin, kidney liver fibrosis. Therefore, we reason...
With the aim of expediting drug target discovery and validation for respiratory diseases, we developed an optimized method in situ somatic gene disruption murine lung epithelial cells via AAV6-mediated CRISPR-Cas9 delivery. Efficient editing was observed type II alveolar distal airway following assessment single- or dual-guide AAV vector formats, Cas9 variants, a sequential dosing strategy with combinatorial guide RNA expression cassettes. In particular, were able to demonstrate...
Abstract Vascular leakage, or edema, is a serious complication of acute allergic reactions. leakage triggered by the release histamine and serotonin from granules within tissue-resident mast cells. Here, we show that expression Neutrophil Serine Protease 4 (NSP4) during early stages cell development regulates cell-mediated vascular leakage. In myeloid precursors, granulocyte–macrophage progenitors (GMPs), loss NSP4 results in decrease cellular levels histamine, heparin/heparan sulfate. Mast...
Screening of the Merck compound collection identified 6 as an unusually simple, low molecular weight hit with moderate affinity for GABAA receptors. The structural novelty 6, compared to our advanced series alpha5 inverse agonists, made it attractive molecule further exploration. This paper will describe evolution into a new ligands nanomolar and functional selectivity receptor subtypes.
The ability of stem cells to rapidly proliferate and differentiate is integral the steady-state maintenance tissues with high turnover such as blood intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies defects in barrier function. Rho-kinases, Rock1 Rock2, regulate cell shape cytoskeletal rearrangement, activities essential mitosis. Here, we use inducible gene targeting ablate Rock2 adult mice, identify an obligate requirement for enzymes...
ABSTRACT Peg10 (paternally expressed gene 10) is an imprinted that essential for placental development. It thought to derive from a Ty3-gyspy LTR (long terminal repeat) retrotransposon and retains Gag Pol-like domains. Here we show the domain of PEG10 can promote vesicle budding similar HIV p24 protein. Expressed in subset mouse endocrine organs addition placenta, was identified as substrate deubiquitinating enzyme USP9X. Consistent with having critical role development, PEG10-deficient...