A5026992665- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiac Fibrosis and Remodeling
- Wnt/β-catenin signaling in development and cancer
- S100 Proteins and Annexins
- Neuroscience and Neuropharmacology Research
- Immune cells in cancer
- Nuclear Receptors and Signaling
- Cardiac electrophysiology and arrhythmias
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Lysosomal Storage Disorders Research
- Cardiovascular Effects of Exercise
- Advanced Neuroimaging Techniques and Applications
- Biochemical and Molecular Research
- Helicobacter pylori-related gastroenterology studies
- Lanthanide and Transition Metal Complexes
- Cholinesterase and Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Signaling Pathways in Disease
- Metabolism and Genetic Disorders
- Cardiac Ischemia and Reperfusion
- Immune Response and Inflammation
- RNA regulation and disease
- Cancer, Hypoxia, and Metabolism
Takeda (United States)
2024-2025
Centre for Addiction and Mental Health
2019-2022
University of Toronto
2019-2022
Eisai (United States)
2019
Beth Israel Deaconess Medical Center
2011-2017
Johns Hopkins University
2012
Dana-Farber Cancer Institute
2012
West Virginia University
2012
Johns Hopkins Medicine
2012
Harvard University
2012
Background— Heart failure is a growing cause of morbidity and mortality. Cardiac phosphatidylinositol 3-kinase signaling promotes cardiomyocyte survival function, but it paradoxically activated in heart failure, suggesting that chronic activation this pathway may become maladaptive. Here, we investigated the downstream effector, serum- glucocorticoid-regulated kinase-1 (SGK1), its complications. Methods Results— We found cardiac SGK1 human murine failure. role by using cardiac-specific...
CBD-2115 was selected from a library of 148 compounds based on pyridinyl-indole scaffold as first-in-class 4R-tau radiotracer. In vitro binding assays showed [3H]CBD-2115 had KD value 6.9 nM and nominal Bmax 500 in expressing P301L transgenic mouse tissue. with human brain tissue homogenates, has higher affinity (4.9 nM) for progressive supranuclear palsy specific deposits than [3H]flortaucipir (45 or [3H]MK-6240 (>50 nM). [18F]CBD-2115 reliably synthesized (3–11% radiochemical yield molar...
The mTORC1 inhibitor DDiT4L prevents the increase in heart size caused by stress.
Using structure-guided design, several cell based assays, and microdosed positron emission tomography (PET) imaging, we identified a series of highly potent, selective, brain-penetrant oxazole-4-carboxamide-based inhibitors glycogen synthase kinase-3 (GSK-3). An isotopologue our first-generation lead, [3H]PF-367, demonstrates selective specific target engagement in vitro, irrespective the activation state. We discovered substantial ubiquitous GSK-3-specific radioligand binding Tg2576...
Microglia play a role in several central nervous system (CNS) diseases and are highly sought target for positron emission tomography (PET) imaging therapeutic intervention. 5-Cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide ([11C]CPPC) is radiopharmaceutical designed to selectively microglia via macrophage colony stimulating factor-1 receptor (CSF-1R) the CNS. Herein, we report first preclinical evaluation of [3H]CPPC using radioligand binding methods...
Abstract Chronic traumatic encephalopathy is a neurological disorder associated with head trauma and confirmed upon autopsy. PET imaging of chronic may provide means to move towards ante-mortem diagnosis therapeutic intervention following brain injuries. Characterization the neuroinflammatory biomarkers, 18 kDa translocator protein monoamine oxidase-B was conducted using [3H]PBR-28 [3H]L-deprenyl, respectively, in post-mortem tissue. displayed high specific binding both (95.40 ± 1.87%; n =...
Glycogen synthase kinase-3 (GSK-3) is a positron emission tomography (PET) imaging target with implications in the pathogenesis of Alzheimer's disease (AD). This preliminary study evaluates human AD and transgenic P301L mouse brain tissues using GSK-3-targeting radiotracers [3H]PF-367 [3H]OCM-44 radioligand binding assays. A saturation analysis showed decreased GSK-3 density female compared to normal healthy brain. Equivalence (Bmax), affinity (Kd), apparent (Ki) both was demonstrated enable...
Introduction: DDiT4L is a known negative regulator of mTOR signaling in skeletal muscle; however its role the heart unknown. We have recently showed increased mRNA murine transgenic model pathological but not physiological hypertrophy. Here we test hypothesis that and may play hypertrophy failure. Methods: investigated regulation models cultured neonatal rat ventricular cardiomyocytes (NRVMs). Loss gain function autophagy was using confocal imaging, immunoblotting, qRT-PCR NRVMs. Results:...