A5031048434- Chemical Synthesis and Analysis
- Liver Disease Diagnosis and Treatment
- Diet, Metabolism, and Disease
- Monoclonal and Polyclonal Antibodies Research
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Lipid metabolism and biosynthesis
- Cancer-related molecular mechanisms research
- Kruppel-like factors research
- Mathematical Biology Tumor Growth
- Neurotransmitter Receptor Influence on Behavior
- Single-cell and spatial transcriptomics
- Receptor Mechanisms and Signaling
- Fibroblast Growth Factor Research
- Gene Regulatory Network Analysis
- Biochemical and Molecular Research
- Mitochondrial Function and Pathology
- Lipid metabolism and disorders
University of Pennsylvania
2018-2024
University of Delaware
2017-2020
In response to a meal, insulin drives hepatic glycogen synthesis help regulate systemic glucose homeostasis. The mechanistic target of rapamycin complex 1 (mTORC1) is well-established and contributes the postprandial control liver lipid metabolism, autophagy, protein synthesis. However, its role in metabolism less understood. Here, we used metabolomics, isotope tracing, mouse genetics define for mTORC1 signaling glycolytic intermediates deposition. We show that required synthase activity...
Protein C-terminal hydrazides are useful for bioconjugation and construction of proteins from multiple fragments through native chemical ligation. To generate in proteins, an efficient intein-based preparation method has been developed by using thiols hydrazine to accelerate the formation transient thioester intermediate subsequent hydrazinolysis. This approach not only increases yield, but also improves biocompatibility. The scope expanded employing Pyrococcus horikoshii RadA split intein,...
Abstract The hepatic transcription factor forkhead box O1 (FOXO1) is a critical regulator of and systemic insulin sensitivity. Previous work by our group others demonstrated that genetic inhibition FOXO1 improves sensitivity both in dietary mouse models metabolic disease. Mechanistically, this due part to cell nonautonomous control adipose tissue However, the mechanisms mediating liver-adipose crosstalk remain ill defined. One candidate hepatokine controlled fibroblast growth 21 (FGF21)....
The insulin responsive Akt and FoxO1 signaling axis is a key regulator of the hepatic transcriptional response to nutrient intake. Here, we used global run-on sequencing (GRO-seq) measure nascent fasting refeeding as well define specific role in mediating this response. We identified 599 feeding-regulated transcripts, over 6,000 eRNAs, mapped their dependency on signaling. Further, several lncRNAs, including lncRNA Gm11967, whose expression was dependent upon liver Akt-FoxO1 axis. Restoring...
Recent genome-wide association studies (GWAS) have revealed shared genetic components among alcohol, opioid, tobacco and cannabis use disorders. However, the extent of underlying causal variants effector genes, along with their cellular context, remain unclear. We leveraged our existing 3D genomic datasets comprising high-resolution promoter-focused Capture-C/Hi-C, ATAC-seq RNA-seq across >50 diverse human cell types to focus on regions that coincide GWAS loci. Using stratified LD...
Abstract The incidence of obesity, insulin resistance, and type II diabetes (T2DM) continues to rise worldwide. liver is a central insulin‐responsive metabolic organ that governs whole‐body homeostasis. Therefore, defining the mechanisms underlying action in essential our understanding pathogenesis resistance. During periods fasting, catabolizes fatty acids stored glycogen meet demands body. In postprandial conditions, signals store excess nutrients into triglycerides, cholesterol, glycogen....
The formation of blood clots is vital for biological repair injured vessels. When a vessel injured, platelets come into contact with collagen, causing glycoprotein VI (GPVI) to undergo conformational change and initialize the clotting process. This project aimed simplify solve system coupled ordinary differential equations (ODEs) proposed in Model A Regulation Early Steps GPVI Signal Transduction by Phosphatase: Systems Biology Approach JL Dunster et al., modeling early platelet activation...
Peptide hydrazides are powerful surrogates for the thioesters typically used in protein ligation as well being an effective handle labeling. Typical peptide hydrazide preparation relies on solid‐phase synthesis, a technique limited by size and solubility that also uses harsh chemicals. Here, more biochemically‐friendly means of generating these has been established involving split PhoRadA inteins, which only regain their splicing activity upon association with each other. This method avoids...
Hydrazides at proteins’ C termini are much desired because of their straightforward use for bioconjugations and chemical modifications. However, traditional preparation methods often lack the necessary biocompatibility. In full paper, J. Liu, S. Rozovsky, et al. on page 346 in Issue 3, 2020 (DOI: 10.1002/cbic.201900160) show that combining thiols hydrazine under mild conditions results high-yield generation such C-terminal hydrazides. The addition not only accelerates formation transient...