A5014935092- Cancer Research and Treatments
- Osteoarthritis Treatment and Mechanisms
- Wnt/β-catenin signaling in development and cancer
- Cell Image Analysis Techniques
- Genomics and Phylogenetic Studies
- Glioma Diagnosis and Treatment
- Genetics, Bioinformatics, and Biomedical Research
- Cancer Genomics and Diagnostics
- Radiomics and Machine Learning in Medical Imaging
- Molecular Biology Techniques and Applications
- RNA Research and Splicing
- Knee injuries and reconstruction techniques
- 3D Printing in Biomedical Research
- Bone fractures and treatments
- Bioinformatics and Genomic Networks
- Artificial Intelligence in Healthcare and Education
- Neurobiology and Insect Physiology Research
- Protease and Inhibitor Mechanisms
- Online Learning and Analytics
- Spectroscopy Techniques in Biomedical and Chemical Research
- Optical Imaging and Spectroscopy Techniques
- Down syndrome and intellectual disability research
- Tendon Structure and Treatment
- Animal Behavior and Reproduction
- Cardiac Fibrosis and Remodeling
Temple University
2024
Portland VA Medical Center
2021
Samumed (United States)
2017-2021
University of California, San Diego
2007-2017
Joint Genome Institute
2003
Rhodopseudomonas palustris is among the most metabolically versatile bacteria known. It uses light, inorganic compounds, or organic for energy. acquires carbon from many types of green plant–derived compounds by dioxide fixation, and it fixes nitrogen. Here we describe genome sequence R. palustris, which consists a 5,459,213-base-pair (bp) circular chromosome with 4,836 predicted genes plasmid 8,427 bp. The reveals that confer remarkably large number options within given type metabolism,...
<h2>Summary</h2><h3>Objectives</h3> Osteoarthritis (OA) is a degenerative disease characterized by loss of cartilage and increased subchondral bone within synovial joints. Wnt signaling affects the pathogenesis OA as this pathway modulates both differentiation osteoblasts chondrocytes, production catabolic proteases. A novel small-molecule inhibitor, SM04690, was evaluated in series <i>in vitro</i> vivo</i> animal studies to determine its effects on chondrogenesis, protection synovial-lined...
ObjectivesWnt pathway upregulation contributes to knee osteoarthritis (OA) through osteoblast differentiation, increased catabolic enzymes, and inflammation. The small-molecule Wnt inhibitor, lorecivivint (SM04690), which previously demonstrated chondrogenesis cartilage protection in an animal OA model, was evaluated elucidate its mechanism of action.DesignBiochemical assays measured kinase activity. Western blots protein phosphorylation human mesenchymal stem cells (hMSCs), chondrocytes,...
The Wnt/β-catenin signaling pathway is aberrantly activated in colorectal (CRC) and many other cancers, novel strategies for effectively targeting it may be needed due to its complexity. In this report, SM08502, a small molecule clinical development the treatment of solid tumors, was shown reduce Wnt gene expression through potent inhibition CDC-like kinase (CLK) activity. SM08502 inhibited serine arginine rich splicing factor (SRSF) phosphorylation disrupted spliceosome activity, which...
In Down syndrome (DS) or trisomy of chromosome 21, the β-amyloid (Aβ) peptide product amyloid precursor protein (APP) is present in excess. Evidence points to increased APP gene dose and Aβ as playing a critical role cognitive difficulties experienced by people with DS. Particularly, linked late-life emergence dementia associated neuropathological markers Alzheimer's disease (AD). At present, no treatment targets Aβ–related pathogenesis Herein we used vaccine containing 1–15 embedded into...
Abstract Pre-clinical oncology researchers face significant challenges when identifying suitable tumor models. Suboptimal model selection can impede the translational success of preclinical findings to clinical applications. Traditional online databases rely on rigid filtering systems that may not accommodate complex and specific criteria require. To address this critical need, Certis Oncology developed CertisOI, a Generative AI-powered platform transforms how discover analyze cancer models...
Background: Genomic profiling cannot solely predict the complexity of how tumor cells behave in their vivo microenvironment and susceptibility to therapies. The aim study was establish a functional drug prediction model utilizing patient-derived GBM samples for vitro testing efficacy followed by validation overcome disadvantages strict pharmacogenomics approach. Methods: High-throughput pharmacologic tumors cultured as 3D organoids offered cost-effective, clinically phenotypically relevant...
Data integration is an escalating problem in bioinformatics. We have developed a web tool and warehousing system, Booly, that features simple yet flexible data model coupled with the ability to perform powerful comparative analysis, including use of Boolean logic merge datasets together, integrated aliasing system decipher differing names same gene or protein. Furthermore, Booly collaborative sharing public repository so users can retrieve new while contributors easily disseminate content....
Abstract Dysregulation of alternative pre-mRNA splicing has been identified as a common mechanistic driver tumor initiation, disease progression, and emergence therapy resistance. An iterative screening campaign SM08502, potent pan-inhibitor CDC-like kinases (CLKs), which are known to regulate splicing. In preclinical studies, SM08502 inhibited growth induced apoptosis in broad array models. Study NCT03355066 is two-part Phase 1 first-in-human study that evaluated the safety, tolerability,...
<ns4:p>The single figure publication is a novel, efficient format by which to communicate scholarly advances. It will serve as forerunner of the nano-publication, modular unit information critical for machine-driven data aggregation and knowledge integration.</ns4:p>
e15185 Background: Aberrant activation of Wnt signaling contributing to tumorigenesis is most commonly associated with CRC (90% harbor pathway mutations). SM08502, a novel, oral inhibitor, was evaluated in preclinical models. Methods: In vitro signaling: assessed using TOPflash β-catenin/TCF reporter assay SW480 human cells. gene expression: measured by qRT-PCR and Wnt3a-stimulated cells (HEK-293T, IEC-6), the Nanostring array (180 genes) across panel 16 cell lines. proliferation: 17 lines...
Abstract Accurate prediction of drug response using machine learning (ML) remains a significant challenge in development as well personalized cancer therapy. Furthermore, there is scarcity rigorous external validation studies for evaluating models. Even when available, such validations are often confined to in-vitro studies. Orthotopic patient-derived xenograft (O-PDX) mice serve essential preclinical models that closely replicate the human tumor microenvironment and assess therapeutic...
Abstract Glioblastoma (GBM) is a devastating primary brain cancer with approximately 10,000 new US diagnoses annually. The current standard of care (SOC) for GBM includes surgical resection followed by radiation therapy (RT) and temozolomide (TMZ), however, there near universal recurrence development resistance after treatment. Relapse in disease tightly linked dynamic changes gene expression during tumor evolution, highlighting the need stronger preclinical models. Here, we report...
Abstract Precision oncology seeks to tailor cancer treatments individual patients. Patient-derived xenografts (PDXs) have emerged as a promising platform for selecting efficacious, personalized therapies and developing new drugs. Here, we present workflow validating patients with colorectal (CRC) that integrates orthotopic PDX (O-PDX) models, molecular profiling, machine learning, in vivo pharmacological validation. Of the nine tumor biopsies collected, seven were successfully developed into...
Introduction: The lymphatic vessels play important roles in maintaining tissue fluid homeostasis, intestinal lipid uptake and immune surveillance. Malformation or dysfunction of these are associated with a number diseases, including lymphedema, inflammation, fibrosis, myocardial infarction atherosclerosis etc. Recent studies have shown that stimulation vessel growth could prevent lymphedema improve many disease pathologies, highlighting targeting as novel therapeutic approach for related...
Cardiovascular disease is the leading cause of death worldwide. Despite high prevalence, standard treatments have made little progress, and developing novel therapeutic to improve cardiac diseases top priority field. Lymphatics are essential in maintaining tissue-fluid homeostasis, clearing cell debris, trafficking immune cells. Over recent years, lymphatics emerged as a potential target for treatment cardiovascular diseases, lymphangiogenesis shown function following myocardial infarction...
The availability of complete genome sequence information for diverse organisms including model genetic has ushered in a new era protein comparisons making it possible to search commonalities among entire proteomes using the Basic Local Alignment Search Tool (BLAST). Although identification and analysis proteins shared by humans proven an invaluable tool understanding gene function, sets unique given organism's proteome have remained largely unexplored. We constructed searchable database that...
Abstract Patient derived xenografts (PDX) are increasingly utilized in translational research and drug development. Characterizing the genomic features of PDX is essential to establishing reliable models for cancer research. Despite great interest, problems remain tumor data banks including improper type diagnosis sample mix-ups. In an effort improve annotation quality models, we developed a machine learning model trained on gene expression from The Cancer Genome Atlas (TCGA). We then...
<h3>Background</h3> Emerging evidence highlights the importance of local tumor microenvironment (TME) in evaluating efficacy new therapeutics, especially for immunotherapies. Historically, patient-derived xenograft (PDX) modeling involves subcutaneous implantation which minimally represents actual human site, as opposed to orthotopic (O-PDX) more accurately reflects TME. In this study, we sought determine immunological and functional differences between modeling. <h3>Methods</h3> We...
Abstract Glioblastoma (GBM) is a devastating primary brain cancer with approximately 10,000 new US diagnoses annually. The current standard of care for GBM includes surgical resection followed by radiation therapy (RT) and temozolomide (TMZ), however there near universal recurrence development resistance after treatment. Relapse in disease tightly linked dynamic changes gene expression during tumor evolution, highlighting the need stronger preclinical models. Here we report developing pair...
<h3>Background</h3> In the synovial joint, Wnt pathway upregulation contributes to osteoarthritis (OA) by increasing osteocyte differentiation, cartilage thinning, and inflammation. SM04690, a novel small molecule, has previously demonstrated potential OA disease-modifying effects through inhibition <i>in vitro</i> vivo</i>. <h3>Objectives</h3> To elucidate mechanism of action for SM04690 on inhibition, chondrocyte anti-inflammation. <h3>Methods</h3> activity was measured using cell-based...