A5083207214- Pancreatic function and diabetes
- Congenital heart defects research
- Cancer Cells and Metastasis
- Ubiquitin and proteasome pathways
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Diabetes and associated disorders
- Neonatal Respiratory Health Research
- Alzheimer's disease research and treatments
- Genetic Associations and Epidemiology
- Renal Diseases and Glomerulopathies
- RNA Interference and Gene Delivery
- 3D Printing in Biomedical Research
- Cognitive Abilities and Testing
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Lung Cancer Treatments and Mutations
- Cancer-related Molecular Pathways
- Advanced Breast Cancer Therapies
- Construction Engineering and Safety
- CAR-T cell therapy research
- Cancer, Hypoxia, and Metabolism
- Ferrocene Chemistry and Applications
- Genetics and Neurodevelopmental Disorders
- Congenital Diaphragmatic Hernia Studies
Tempus Labs (United States)
2021-2025
National Institutes of Health
2019
National Cancer Institute
2019
Center for Cancer Research
2019
National Cancer Institute
2017
University of Michigan
2010-2016
University of Colorado Denver
2010
University of Colorado Boulder
2010
University of North Dakota
2006
Mater Health Services
2000
Patient-derived tumor organoids (TOs) are emerging as high-fidelity models to study cancer biology and develop novel precision medicine therapeutics. However, utilizing TOs for systems-biology-based approaches has been limited by a lack of scalable reproducible methods profile these models. We describe robust pan-cancer TO platform with chemically defined media optimized on cultures acquired from over 1,000 patients. Crucially, we demonstrate genetic transcriptomic concordance this approach...
Abstract Hypercholesterolemia is a potential trigger of Alzheimer's disease, and thought to increase brain levels β‐amyloid (Aβ) iron. However, animal models address the mechanisms by which Aβ iron accumulation may cause neuronal damage are poorly defined. To this question, we fed adult rabbits 1% cholesterol‐enriched diet for 7 months. This was associated with increased regional deposition both peptide in brain. Iron preferentially accumulated around plaques adjacent cortex, but not found...
Hox genes are required for proper anteroposterior axial patterning and the development of several organ systems. Here, we show that all three Hox5 paralogous play redundant roles in developing lung. Hoxa5;Hoxb5;Hoxc5 triple-mutant embryos develop severely hypoplastic lungs with reduced branching proximal-distal defects. exclusively expressed lung mesoderm; however, defects observed both mesenchyme endodermally derived epithelium, demonstrating act to regulate mesodermal-epithelial crosstalk...
Despite significant advances in our understanding of pancreatic endocrine cell development, the function mesodermal niche this process is poorly understood. Here we report a novel role for Hox6 genes organogenesis. are expressed exclusively mesoderm developing pancreas. Genetic loss all three paralogs (Hoxa6, Hoxb6, Hoxc6) leads to dramatic endoderm-derived cells including insulin-secreting beta cells, as well mild delays and disruptions pancreas branching exocrine differentiation....
Background: Antibody-drug conjugates (ADCs) such as the HER2-targeting agent trastuzumab deruxtecan, TROP-2 targeting sacituzumab govitecan, and NECTIN4 enfortumab vedotin-ejfv, have resulted in increased clinical response rates previously difficult to treat solid tumor indications, but only a minority of patients exhibit responses. Increased understanding molecular underpinnings sensitivity resistance ADCs beyond membranous target expression is needed. To that end, we developed platform for...
The thymus is critical for the establishment of adaptive immune system and development a diverse T cell repertoire. depends upon cell-cell interactions with epithelial cells in thymus. composed two different types cells: cortical medullary cells. Both these express critically depend on transcription factor Foxn1Foxn1 also expressed hair follicle, disruption Foxn1 function mice results severe thymic developmental defects hairless (nude) phenotype. Despite its importance, little known about...
High-content imaging of tumor organoids (TOs) treated with therapeutic agents provides detailed cell viability readouts at the organoid level. In contrast, most used protocols provide one number per well. While requiring use inverted microscopy an automated stage, this protocol can critical information about heterogeneous responses TOs to various treatments. This describes a technique for culturing and drug testing using fluorescent indicators high reproducibility. For complete details on...
Human RFamide-related peptide-1 (hRFRP-1, MPHSFANLPLRF-NH(2)) binds to neuropeptide FF receptor 2 (NPFF(2)R) dramatically diminish cardiovascular performance. hRFRP-1 and its signaling pathway may provide targets address cardiac dysfunction. Here, structure-activity relationship, transcript, Ca(2+) transient, phospholabeling data indicate the presence of a in cardiomyocytes. Alanyl-substituted N-terminal truncated analogues identified that R(11) was essential for activity, hRFRP-1((8-12))...
Abstract Introduction: Patient-derived organoids (PDOs) enable the ex vivo study of tumor heterogeneity and its effect on response to treatment. Our previous work demonstrated that our robust pan-cancer organoid platform shows genetic transcriptomic concordance with clinical samples can be deployed for high-throughput drug screening. Here, we ran a standard care (SOC) panel PDOs paired de-identified clinically curated data comparison patient same drugs exploration potentially more effective...
Abstract CDK4/6 inhibitors (CDK4/6i) in combination with antiestrogens have revolutionized the treatment of ER+ metastatic breast cancer (MBC), significantly prolonging survival. However, this is not curative, and tumors eventually acquire resistance. Following progression on combination, patients are left limited options. A diverse array mechanisms resistance to CDK4/6i + been described. laboratory models that capture heterogeneity lacking. Patient-derived organoids (PDOs) provide a rapid,...
e13544 Background: Prediction of drug response based on cancer molecular profiles is paramount importance for precision oncology. Most existing prediction models are built using screening data immortalized cell lines, which usually have altered genomic compared with patient tumors. Recently, patient-derived organoids (PDOs) emerging as a promising platform better representing We build computational PDO data, the first study its type to our knowledge. Methods: successfully developed 27 lines...
Background Cell engager and adoptive cell therapeutics have emerged as efficacious durable treatments in patients with B-cell malignancies. Though many analogous strategies are under development solid tumors, none received approval. Preclinical of these therapies requires labeling immortalized lines and/or primary expanded T cells to distinguish target effector cells. However, had limited evidence reproducibility patient-derived models such tumor organoid cultures thus far. Here, we build...