A5047375937- Computability, Logic, AI Algorithms
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Advanced Topology and Set Theory
- Mitochondrial Function and Pathology
- Diabetes Treatment and Management
- semigroups and automata theory
- Adipose Tissue and Metabolism
- ATP Synthase and ATPases Research
- Logic, Reasoning, and Knowledge
- Diet and metabolism studies
- Cancer, Hypoxia, and Metabolism
- Cellular Automata and Applications
- Mathematical Dynamics and Fractals
- Cybersecurity and Cyber Warfare Studies
- Peptidase Inhibition and Analysis
- Liver Disease Diagnosis and Treatment
- Diet, Metabolism, and Disease
- Cardiovascular Function and Risk Factors
- International Law and Human Rights
- Algebraic Geometry and Number Theory
- Adipokines, Inflammation, and Metabolic Diseases
- Cell death mechanisms and regulation
- Rings, Modules, and Algebras
- Autophagy in Disease and Therapy
Pfizer (United States)
2014-2025
University of California, San Diego
2025
EBS University of Business and Law
2020
Max Planck Institute for Research on Collective Goods
2020
University of Strathclyde
2020
Engineering and Physical Sciences Research Council
2020
Washington and Lee University
2008-2020
Cambridge University Press
2020
Queens College, CUNY
2005-2019
University of Pennsylvania
2009-2018
The adipocyte-derived hormone adiponectin signals from the fat storage depot to regulate metabolism in peripheral tissues. Inversely correlated with body levels, reduction obese individuals may play a causal role symptoms of metabolic syndrome. Adiponectin lowers serum glucose through suppression hepatic production, an effect attributed activation AMPK. Here, we investigated signaling pathways that mediate effects by studying mice inducible deletion LKB1, upstream regulator We found loss...
Dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver accumulation ultimately non-alcoholic steatohepatitis (NASH). Therapeutic activators the AMP-Activated Protein Kinase (AMPK) have been proposed as treatment for metabolic diseases; we show that AMPK β1-biased activator PF-06409577 capable lowering systemic levels both rodent monkey preclinical models. able inhibit de novo synthesis pathways, causes...
Adenosine monophosphate-activated protein kinase (AMPK) is a involved in maintaining energy homeostasis within cells. On the basis of human genetic association data, AMPK activators were pursued for treatment diabetic nephropathy. Identification an indazole amide high throughput screening (HTS) hit followed by truncation to its minimal pharmacophore provided acid lead compound. Optimization core and aryl appendage improved oral absorption culminated identification indole acid, PF-06409577...
Diabetic nephropathy remains an area of high unmet medical need, with current therapies that slow down, but do not prevent, the progression disease. A reduced phosphorylation state adenosine monophosphate-activated protein kinase (AMPK) has been correlated diminished kidney function in both humans and animal models renal Here, we describe identification novel, potent, small molecule activators AMPK selectively activate heterotrimers containing β1 subunit. After confirming human rodent...
Abstract Background Follicular variant papillary thyroid carcinoma is a distinct subtype of that can occasionally present with aggressive features, including distant metastases and extrathyroidal extension. While radioactive iodine ablation well-established treatment for residual disease, its post-treatment effects on tracheal paratracheal structures remain poorly characterized. Case presentation A 22-year-old male individual Taiwanese descent presented an enlarged neck mass was diagnosed...
Branched chain amino acid (BCAA) catabolic defects are implicated to be causal determinates of multiple diseases. This work aimed better understand how enhancing BCAA catabolism affected metabolic homeostasis as well the mechanisms underlying these improvements. The rate limiting step is irreversible decarboxylation by branched ketoacid dehydrogenase (BCKDH) enzyme complex, which post-translationally controlled through phosphorylation BCKDH kinase (BDK). study utilized BT2, a small molecule...
Branched chain amino acid (BCAA) catabolic impairments have been implicated in several diseases. ketoacid dehydrogenase (BCKDH) controls the rate limiting step BCAA degradation, activity of which is inhibited by BCKDH kinase (BDK)-mediated phosphorylation. Screening efforts to discover BDK inhibitors led identification thiophene PF-07208254, improved cardiometabolic endpoints mice. Structure-activity relationship studies a thiazole series inhibitors; however, these did not improve metabolism...
Heart failure with preserved ejection fraction (HFpEF) is increasingly common but its pathogenesis poorly understood. The ability to assess genetic and pharmacologic interventions hampered by the lack of robust preclinical mouse models HFpEF. We developed a novel "two-hit" model, which combines obesity insulin resistance chronic pressure overload recapitulate clinical features C57Bl6/NJ mice fed high-fat diet (HFD) for > 10 weeks were administered an AAV8-driven vector resulting in...
Parallel to major changes in fatty acid and glucose metabolism, defect branched-chain amino (BCAA) catabolism has also been recognized as a metabolic hallmark potential therapeutic target for heart failure. However, BCAA catabolic enzymes are ubiquitously expressed all cell types systemic is manifested disorder associated with obesity diabetes. Therefore, it remains be determined the cell-autonomous impact of cardiomyocytes intact hearts independent from its global effects. In this study, we...
Abstract We characterize the structure of computably categorical trees finite height, and prove that our criterion is both necessary sufficient. Intuitively, characterization easiest to express in terms isomorphisms (possibly infinite) trees, but fact it equivalent a -condition. show all which are not have computable dimension ω. Finally, we for every n ≥ 1 ω, there exists tree height Σ 3 0 -categorical Δ
Skeletal muscle is an attractive target for blood glucose-lowering pharmacological interventions. Oral dosing of small molecule direct pan-activators AMPK that bind to the allosteric drug and metabolite (ADaM) site, lowers glucose through effects in skeletal muscle. The molecular mechanisms responsible this effect are not described detail. This study aimed illuminate by which ADaM-site activators increase uptake Further, we investigated consequence co-stimulating muscles with two types i.e.,...