A5034390507- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Lanthanide and Transition Metal Complexes
- Parkinson's Disease Mechanisms and Treatments
- Pregnancy and preeclampsia studies
- Nanocluster Synthesis and Applications
- Tryptophan and brain disorders
- Advanced Neuroimaging Techniques and Applications
- Luminescence and Fluorescent Materials
- Advanced MRI Techniques and Applications
- Maternal and fetal healthcare
- MRI in cancer diagnosis
- Click Chemistry and Applications
- Ectopic Pregnancy Diagnosis and Management
- Nanoplatforms for cancer theranostics
- Barrier Structure and Function Studies
- Neurological disorders and treatments
- S100 Proteins and Annexins
- Advanced X-ray and CT Imaging
- Radiomics and Machine Learning in Medical Imaging
- Enzyme Catalysis and Immobilization
- Medical Imaging Techniques and Applications
- X-ray Diffraction in Crystallography
- Synthesis and Biological Evaluation
- Bioactive Compounds and Antitumor Agents
Baylor College of Medicine
2012-2025
Texas Children's Hospital
2014-2025
The University of Texas Health Science Center at Houston
2012
University of Houston
2010
Utah State University
2008-2009
University of Sheffield
2008-2009
The University of Texas Medical Branch at Galveston
2009
Australian National University
2008
Middlebury College
2008
The University of Queensland
2008
Abstract The first line of treatment for most solid tumors is surgical resection the primary tumor with adequate negative margins. Incomplete resections positive margins account over 75% local recurrences and development distant metastases. In cases oral cavity squamous cell carcinoma (OSCC), rate successful removal just 50–75%. Advanced real‐time imaging methods that improve detection can help success rates,overall safety, reduce cost. Fluorescence in second near‐infrared (NIR‐II) window...
Extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles constitute the major neuropathological hallmarks of Alzheimer’s disease (AD). It is now apparent that parenchymal Aβ plaque deposition precedes behavioral signs by several years. The development agents can target these may be useful as diagnostic or therapeutic tools. In this study, we synthesized an Aβ-targeted lipid conjugate, incorporated it in stealth liposomal nanoparticles tested their ability to bind...
The glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes is a promiscuous binuclear metallohydrolase that catalyzes the hydrolysis of mono-, di-, and triester substrates, including some organophosphate pesticides products degradation nerve agents. GpdQ has attracted recent attention as promising enzymatic bioremediator. Here, we have investigated catalytic mechanism this versatile enzyme using range techniques. An improved crystal structure (1.9 Å resolution) illustrates presence (i)...
Amyloid binding molecules with greater hydrophilicity than existing ligands were synthesized. The lead candidate ET6-21 bound amyloid fibrils, and deposits in dog brain human tissue ex vivo. ligand was used to prepare novel amyloid-targeted liposomal nanoparticles. prepara tion tested the Tg2576 TetO/APP mouse models of deposition. Gd chelates Indocyanine green included particles for visualization by MRI near-infrared microscopy. Upon intravenous injection, successfully traversed blood-brain...
The reaction catalyzed by the protein phosphatase-1 (PP1) has been examined linear free energy relationships and kinetic isotope effects. With substrate 4-nitrophenyl phosphate (4NPP), exhibits a bell-shaped pH-rate profile for kcat/KM indicative of catalysis both acidic basic residues, with pKa values 6.0 7.2. enzymatic hydrolysis series aryl monoester substrates yields Brønsted βlg −0.32, considerably less negative than that uncatalyzed dianions (−1.23). Kinetic effects in leaving group...
Inflammation drives the degradation of atherosclerotic plaque, yet there are no non-invasive techniques available for imaging overall inflammation in plaques, especially coronary arteries. To address this, we have developed a clinically relevant system to image inflammatory cell burden plaque. Here, describe targeted contrast agent (THI0567-targeted liposomal-Gd) that is suitable magnetic resonance (MR) and binds with high affinity selectivity integrin α4β1(very late antigen-4, VLA-4), key...
In Alzheimer's disease (AD), there is increasing evidence of blood–brain barrier (BBB) compromise, usually observed as ‘microbleeds’ correlated with amyloid plaque deposition and apoE- ε4 status, raising the possibility nanotherapeutic delivery. Molecular probes have been used to study neurovascular leak, but this approach does not adequately estimate vascular permeability nanoparticles. We therefore characterized cerebrovascular leaks in live APP+ transgenic animals using a long circulating...
The pathogenesis of Parkinson’s disease (PD) is characterized by progressive deposition alpha-synuclein (α-syn) aggregates in dopaminergic neurons and neuroinflammation. Noninvasive vivo imaging α-syn aggregate accumulation neuroinflammation can elicit the underlying mechanisms involved progression facilitate development effective treatment as well diagnosis prognosis. Here we present a novel approach to simultaneously profile aggregation reactive microgliosis , targeting oligomeric...
Reactivities of five phosphonate esters each coordinated to a dinuclear Co(III) complex were investigated ([Co2(tacn)2(OH)2{O2P(Me)OAr}]3+; tacn = 1,4,7-triazacyclononane; substituent m-F, p-NO2 (1a); (1b); m-NO2 (1c); p-Cl (1d); unsubstituted (1e)). Hydrolysis the in 1a 1e is specific base catalyzed and takes place by intramolecular oxide attack on bridging phosphonate. These data define Brønsted βlg −1.12, considerably more negative than that hydrolysis uncomplexed phosphonates (−0.69)....
Abstract Non-invasive methods for estimating placental fractional blood volume (FBV) are of great interest characterization vascular perfusion in placentae during pregnancy to identify insufficiency that may be indicative local ischemia or fetal growth restriction (FGR). Nanoparticle contrast-enhanced magnetic resonance imaging (CE-MRI) enable direct FBV estimation and provide a reliable, 3D alternative assess maternal-side perfusion. In this pre-clinical study, we investigated if at 14, 16,...
Abstract In these preclinical studies, we describe ADx-001 , an Aβ-targeted liposomal macrocyclic gadolinium (Gd) imaging agent, for MRI of amyloid plaques. The targeting moiety is a novel lipid-PEG conjugated styryl-pyrimidine. An MRI-based contrast agent such as attractive because the lack radioactivity, ease distribution, long shelf life, and prevalence scanners. Dose-ranging efficacy studies were performed on 1 T scanner using transgenic APP/PSEN1 mouse model Alzheimer’s disease. was...
Three new diarylheptanoids, (4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta-4,6-dien-3-one, letestuianin A (1), (4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-4,6-dien-3-one, B (2), and 1,7-bis(4-hydroxyphenyl)heptan-3,5-dione, C (3), as well the known (4Z,6E)-5-hydroxy-1,7-bis(4-hydroxyphenyl)hepta-4,6-dien-3-one (5) were isolated from Aframomum letestuianum. The flavonoids 3-acetoxy-5,7,4'-trihydroxyflavanone, 3-acetoxy-7-methoxy-5,4'-dihydroxyflavanone,...
Abstract Fluorine-19 ( 19 F) Magnetic Resonance Imaging (MRI) is an emerging modality for molecular imaging and cell tracking. The hydrophobicity of current exogenous probes, perfluorocarbons (PFCs) perfluoropolyethers (PFPEs), limits the formulation options available in vivo applications. Hydrophilic probes permit more flexibility. Further, broad Nuclear (NMR) chemical shift range organofluorine species enables multiple with unique F MR signatures simultaneous interrogation distinct targets...
Boronic acids, known to bind diols, were screened identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates liposomes (Agglomerated Vesicle Technology-AVT). This was done in order select a suitable replacement previously used cross-linker, ConcanavalinA (ConA), lectin have both toxic inflammatory effects vivo. Lead-compounds selected from screens that involved testing potential, cytotoxicity glucose-binding. These then conjugated...
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The development of imaging agents for in vivo detection alpha-synuclein (α-syn) pathologies faces several challenges. A major gap the field is lack diverse molecular scaffolds with high affinity and selectivity to α-syn fibrils vitro screening assays. Better can instruct discovery better agents. We report rational design, synthesis, evaluation a series novel 1-indanone 1,3-indandione derivatives from Structure-Activity Relationship (SAR) study centered on some existing fibril binding...
Fluorine-19 ( 19 F) magnetic resonance imaging (MRI) has the potential for a wide range of in vivo applications but is limited by lack flexibility exogenous probe formulation. Most F MRI probes are composed perfluorocarbons (PFCs) or perfluoropolyethers (PFPEs) with intrinsic properties which limit formulation options. Hydrophilic organofluorine molecules can provide more We report herein hyperfluorinated hydrophilic organoflourine, ET1084 , ∼24 wt. % content. It dissolves water and aqueous...
The abnormal phosphorylation of tau is a necessary precursor to the formation fibrils, marker Alzheimer's disease.We hypothesize that hyperphosphorylative conditions may result in unique cell surface markers.We identify and demonstrate utility such surrogate markers state.Methods: Cell SELEX was used novel thioaptamers specifically binding cells.Cell vimentin identified as potential target aptamer.Novel molecular magnetic resonance imaging (M-MRI) probes using these aptamers small molecule...
Abstract Background Hyperphosphorylated tau (pTau) is a precursor to tangle formation in Alzheimer's disease (AD). We have identified aptamers that bind specific cell membrane receptors of human neuronal cells are hyperphosphorylating tau. In this work, we built novel targeted nanoparticle magnetic resonance imaging (MRI) contrast agent, TauX, binds such neurons, and tested its efficacy vivo the P301S mouse model pathology. Method DNA preferentially binding on hyperphosphorylative SH‐SY5Y...
This paper reports the use of annulation reaction between Fischer carbene complexes and alkynes to provide a collection 78 endiones. In course work, new stannyl silyl endiones were synthesized converted iodides that useful precursor for Suzuki coupling. reactions also performed on derived from bromophenyl providing series cyclohexen-1,4-diones.