A5050134822- Fibroblast Growth Factor Research
- Adipose Tissue and Metabolism
- RNA regulation and disease
- Diet and metabolism studies
- Mesenchymal stem cell research
- Cancer, Hypoxia, and Metabolism
- Nuclear Receptors and Signaling
- Adipokines, Inflammation, and Metabolic Diseases
- Lipoproteins and Cardiovascular Health
- Kruppel-like factors research
- GDF15 and Related Biomarkers
- Metabolism, Diabetes, and Cancer
- Angiogenesis and VEGF in Cancer
- Metabolomics and Mass Spectrometry Studies
- T-cell and B-cell Immunology
- Muscle Physiology and Disorders
- Advanced Proteomics Techniques and Applications
- Genetics, Aging, and Longevity in Model Organisms
- Ubiquitin and proteasome pathways
- Human Pose and Action Recognition
- Pressure Ulcer Prevention and Management
- Diabetes and associated disorders
- Dermatology and Skin Diseases
- Single-cell and spatial transcriptomics
- Galectins and Cancer Biology
Enzo Life Sciences (United States)
2022-2024
Genentech
2014
Understanding the regulation of islet cell mass has important implications for discovery regenerative therapies diabetes. The liver plays a central role in metabolism and endocrine number, but liver-derived factors that regulate α-cell β-cell remain unidentified. We propose nutrient-sensing circuit between pancreas which glucagon-dependent control hepatic amino acid regulates mass. found glucagon receptor inhibition reduced catabolism, increased serum acids, induced proliferation an...
Antibody-mediated activation of fibroblast growth factor receptor 1 reverses the diabetic phenotype in mice, likely by affecting brown adipose tissues.
FGF21 is a stress-induced hormone with potent anti-obesity, insulin-sensitizing, and hepatoprotective properties. Although proteolytic cleavage of recombinant human in preclinical species has been observed previously, the regulation endogenously produced not well understood. Here we identify fibroblast activation protein (FAP) as enzyme that cleaves inactivates FGF21. A selective chemical inhibitor, immunodepletion, or genetic deletion Fap stabilized serum. In addition, administration FAP...
Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT) has been proposed a potential treatment for obesity-linked disorders. Here, we describe the generation humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR) 1/βKlotho complex, common FGF21 and FGF19. Using this molecule, show antibody-mediated activation FGFR1/βKlotho complex in mice induces sustained energy expenditure BAT, browning white tissue,...
Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result amputation morbidity. Although multiple approaches used clinically to help wound closure, many still lack adequate treatment. Here we show that IL-20 subfamily cytokines upregulated during normal healing. While there is a redundant role for each individual cytokine this healing, mice deficient IL-22R, common receptor chain IL-20, IL-22, IL-24, display significant delay Furthermore, IL-22...
We introduce neutron-encoded (NeuCode) amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model Bap1, tumor suppressor and deubiquitinase whose vivo roles outside cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation cholesterol biosynthetic machinery coincident with reduced expression gluconeogenic lipid...
Abstract Nicotinamide adenine dinucleotide (NAD) levels decline during aging, contributing to physical and metabolic dysfunction. The NADase CD38 plays a key role in age‐related NAD decline. Whether the inhibition of increases lifespan is not known. Here, we show that inhibitor 78c healthspan naturally aged mice. In addition 10% increase median survival, improved exercise performance, endurance, function effects were different between sexes. Our study first investigate effect animals.
Abstract Aim Characterize Growth Differentiation Factor 15 (GDF15) as a secreted biomarker of the integrated stress response (ISR) within central nervous system (CNS). Methods We determined GDF15 levels utilizing in vitro and vivo neuronal systems wherein ISR was activated. Primarily, we used murine model vanishing white matter disease (VWMD), neurological driven by persistent CNS, to establish link between cerebrospinal fluid (CSF) gene expression signature CNS. also CSF VWM patients....
The phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) controls phosphate homeostasis by regulating renal expression of sodium-dependent co-transporters and cytochrome P450 enzymes involved in vitamin D catabolism. Multiple FGF Receptors (FGFRs) can act as receptors for FGF23 when bound the co-receptor Klotho expressed tubular epithelium. FGFRs also regulate skeletal secretion; ectopic FGFR activation is implicated genetic conditions associated with overproduction hypophosphatemia....
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...
Diversity Outbred (DO) mice are a powerful model system for mapping complex traits due to their high genetic diversity and resolution. However, while there extensive tools available standard analysis in DO mice, fewer techniques have been implemented facilitate integrated, cross-study analysis. Here, we implement Haseman-Elston regression estimate correlations among 7,233 phenotypes measured across eleven independent mouse studies. We used this network of cluster according shared genetics,...
We present a method to infer the 3D pose of mice, including limbs and feet, from monocular videos. Many human clinical conditions their corresponding animal models result in abnormal motion, accurately measuring motion at scale offers insights into health. The poses improve classification health-related attributes over 2D representations. inferred are accurate enough estimate stride length even when feet mostly occluded. This could be applied as part continuous monitoring system...
Abstract Pregnancy‐associated plasma protein‐A (PAPP‐A) is a secreted metalloprotease that increases insulin‐like growth factor (IGF) availability by cleaving IGF‐binding proteins. Reduced IGF signaling extends longevity in multiple species, and consistent with this, PAPP‐A deletion lifespan healthspan; however, the mechanism remains unclear. To clarify PAPP‐A’s role, we developed neutralizing antibody treated adult mice it. Transcriptomic profiling across tissues showed anti‐PAPP‐A reduced...
Systemic lupus erythematosus is a common autoimmune inflammatory disease which associated with increases in autoantibodies and immune complexes that deposit the kidney. The MRL-lpr mouse model used for study of complex glomerulonephritis but very little known about plasma proteome changes this model. We performed in-depth quantitative profiling on control (strain MpJ) mice to investigate proteome, immunoglobulins their glycoproteome as well protein complexes. Methodologies included...
Abstract eIF2B is a decameric guanine nucleotide exchange factor (GEF) that essential for protein synthesis and key effector of the integrated stress response (ISR). Hypomorphic mutations in any subunits are associated with Vanishing White Matter Disease (VWM), leukodystrophy characterized by ISR activation white matter loss. Here, we showed VWM-associated N208Y eIF2Bα mutation, which abolishes sugar phosphate binding, led to drastic reduction its level cells concomitant activation. We found...
Provide scientific rationale and clinical approach to test ABBV-CLS-7262 as a novel therapy for Vanishing White Matter disease
Abstract Blood plasma is one of the most commonly analyzed and easily accessible biological samples. Here, we describe an automated liquid-liquid extraction (LLE) platform that generates accurate, precise, reproducible samples for metabolomic, lipidomic, proteomic analyses from a single aliquot while minimizing hands-on time avoiding contamination plasticware. We applied mass spectrometry to examine metabolome, lipidome, proteome 90 determine effects age, day, high-fat diet in mice. From 25...
Blood plasma is one of the most commonly analyzed and easily accessible biological samples. Here, we describe an automated liquid-liquid extraction platform that generates accurate, precise, reproducible samples for metabolomic, lipidomic, proteomic analyses from a single aliquot while minimizing hands-on time avoiding contamination plasticware. We applied mass spectrometry to examine metabolome, lipidome, proteome 90 determine effects age, day, high-fat diet in mice. From 25 μl mouse...
Abstract Reducing insulin-like growth factor (IGF) signaling is one of the best conserved and characterized mechanisms to extend longevity. Pregnancy associated plasma protein A (PAPP-A) a secreted metalloprotease that increases IGF availability by cleaving binding proteins. PAPP-A inhibition reduces local signaling, limits progression multiple age-related diseases, extends lifespan, but behind these pleiotropic effects remains unknown. Here, we developed utilized neutralizing antibody...