A5000034398- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Receptor Mechanisms and Signaling
- Adenosine and Purinergic Signaling
- Pharmacological Receptor Mechanisms and Effects
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neuroscience and Neuropharmacology Research
- Immune cells in cancer
- Inhalation and Respiratory Drug Delivery
- Healthcare professionals’ stress and burnout
- Glutathione Transferases and Polymorphisms
- Coordination Chemistry and Organometallics
- Chemical Reaction Mechanisms
- Cerebrovascular and Carotid Artery Diseases
- Neurotransmitter Receptor Influence on Behavior
- Cancer, Hypoxia, and Metabolism
- Pain Mechanisms and Treatments
- Immune Response and Inflammation
- Cyclization and Aryne Chemistry
- Atherosclerosis and Cardiovascular Diseases
- Respiratory Support and Mechanisms
- Synthesis and Properties of Aromatic Compounds
- Energetic Materials and Combustion
- Protein Degradation and Inhibitors
- Renal cell carcinoma treatment
University of Pittsburgh
2020-2025
University of Pittsburgh Medical Center
2023-2024
UPMC Presbyterian
2023
Presbyterian Hospital
2023
Dartmouth College
2015-2020
National Institutes of Health
2017-2019
National Institute of Diabetes and Digestive and Kidney Diseases
2017-2019
Institute of Bioorganic Chemistry
2017-2018
National Cancer Institute
2014-2015
Center for Cancer Research
2014-2015
The lack of techniques for noninvasive imaging inflammation has challenged precision medicine management acute respiratory distress syndrome (ARDS). Here, we determined the potential positron emission tomography (PET) chemokine-like receptor-1 (CMKLR1) to monitor lung in a murine model lipopolysaccharide-induced injury. Lung uptake CMKLR1-targeting radiotracer, [ 64 Cu]NODAGA-CG34, was significantly increased injury, correlated with expression multiple inflammatory markers, and reduced by...
Tryptophan indole 15N–1H signals are well separated in nuclear magnetic resonance (NMR) spectra of proteins. Assignment the therefore enables one to obtain site-specific information on complex proteins supramacromolecular systems, even when extensive assignment backbone resonances is challenging. Here we exploit unique chemical shift by introducing extrinsic tryptophan reporter residues at judiciously chosen locations a membrane protein for increased coverage structure and function NMR. We...
Physiological responses to nociceptive stimuli are initiated within tens of milliseconds, but the corresponding sub-second behavioral have not been adequately explored in awake, unrestrained animals. A detailed understanding these is crucial for progress pain neurobiology. Here, high-speed videography during Aδ fiber stimulation demonstrated engagement a multi-segmental motor program coincident with, or even preceding, withdrawal stimulated paw. The included early head orientation and...
Precision management of fibrotic lung diseases is challenging due to their diverse clinical trajectories and lack reliable biomarkers for risk stratification therapeutic monitoring. Here, we validated the accuracy CMKLR1 as an imaging biomarker inflammation-fibrosis axis. By analyzing single-cell RNA sequencing datasets, demonstrated
(N)-Methanocarba ([3.1.0]bicyclohexyl) adenosines and corresponding ribosides were synthesized to identify novel A1 adenosine receptor (A1AR) agonists for CNS or peripheral applications. Human mouse AR binding was determined assess the constrained ring system's A1AR compatibility. N6-Dicyclobutylmethyl ribose agonist (9, MRS7469, >2000-fold selective A1AR) known truncated N6-dicyclopropylmethyl methanocarba 7 (MRS5474) drug-like. The pure diastereoisomer of riboside 4 displayed high hA1AR...
A three-step synthesis of masked 2,3-diaminoindole 1 from 2-iodo-3-nitro-1-(phenylsulfonyl)indole (2) has been developed. Treatment with trifluoroacetic acid generates the unstable 2,3-diamino-1-(phenylsulfonyl)indole (3), which can be trapped α-dicarbonyl compounds to afford 5H-pyrazino[2,3-b]indoles 7-10.
Elucidating the targets and mechanism of action natural products is strategically important prior to drug development assessment potential clinical applications. In this report, we elucidated main product tonantzitlolone (TZL) in clear cell renal carcinoma (CCRCC). We identified TZL as a dual PKCα PKCθ activator vitro, although CCRCC cells its activity was mostly PKCθ-dependent. Through activation PKCθ, induced an insulin resistant phenotype by inhibiting IRS1 PI3K/Akt pathway....
A new synthesis of dibenzo[a,c]anthracene (4) is described that features the generation, from tetrabromo-bis-triflate 1 and phenyllithium, a 1,3,6-naphthotriyne (2) synthetic equivalent trapped with 3 equiv furan to form Diels-Alder tris-adduct 3. subsequent two-step deoxygenation represents first dibenz[a,c]anthracene involves tandem aryne cycloaddition-deoxygenation strategy.
Functionalized antagonist probes of the A<sub>2A</sub> adenosine receptor.
While screening off-target effects of rigid (N)-methanocarba-adenosine 5'-methylamides as A3 adenosine receptor (AR) agonists, we discovered μM binding hits at the δ-opioid (DOR) and translocator protein (TSPO). In an effort to increase OR decrease AR affinity by structure activity analysis this series, antagonist κ-(K)OR appeared in 5'-esters (ethyl 24 propyl 30), which retained TSPO interaction (μM). 7-Deaza modification C2-(arylethynyl)-5'-esters but not 4'-truncation enhanced KOR...
An improved chemical synthesis, site-specific incorporation and enhanced photo-crosslinking ability of tmdF have been demonstrated in the context protein–protein interactions.
Adenines that incorporate known agonist affinity-enhancing substituents are A<sub>3</sub>AR-selective antagonists.
Abstract Background The lack of noninvasive methods for assessment dysregulated inflammation as a major driver fibrosis (i.e., inflammation-fibrosis axis) has been challenge to precision management fibrotic lung diseases. Here, we determined the potential very late antigen-4 (VLA-4)-targeted positron emission tomography (PET) detect in mouse model bleomycin-induced injury. Method Single time-point and longitudinal VLA-4-targeted PET was performed using high-affinity peptidomimetic...