A5102855680- Monoclonal and Polyclonal Antibodies Research
- Vascular Procedures and Complications
- Protein purification and stability
- Receptor Mechanisms and Signaling
- Central Venous Catheters and Hemodialysis
- Venous Thromboembolism Diagnosis and Management
- Virus-based gene therapy research
- Peripheral Artery Disease Management
- Viral Infectious Diseases and Gene Expression in Insects
- Neurotransmitter Receptor Influence on Behavior
- CRISPR and Genetic Engineering
- Intracranial Aneurysms: Treatment and Complications
- Ocular Oncology and Treatments
- Traumatic Brain Injury and Neurovascular Disturbances
- Chemical Synthesis and Analysis
- Transgenic Plants and Applications
- Forensic Toxicology and Drug Analysis
- Vascular Malformations Diagnosis and Treatment
- Glycosylation and Glycoproteins Research
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- HIV Research and Treatment
- Neuroscience of respiration and sleep
- Soft tissue tumor case studies
- Corneal Surgery and Treatments
Neurological Surgery
2009-2024
University of Miami
2014-2024
University of Arkansas for Medical Sciences
2013-2023
Abound Bio (United States)
2020
University of Pennsylvania
2020
Children's Hospital of Philadelphia
2020
Florida Atlantic University
2020
Boca Raton Regional Hospital
2020
Thomas Jefferson University
2019
University of Pittsburgh Medical Center
2019
The control of cerebral blood flow is complex, and only beginning to be elucidated. Studies have identified three key regulatory paradigms. first pressure autoregulation, which maintains a constant in the face changing perfusion pressure. Flow-metabolism coupling refers brains ability vary match metabolic activity. An extensive arborization perivascular nerves also serves modulate flow, so-called neurogenic regulation. Central these paradigms are two cell types: endothelium astrocytes....
The technological advances in mass spectrometry allow us to collect more comprehensive data with higher quality and increasing speed. With the rapidly amount of generated, need for streamlining analyses becomes apparent. Proteomics is known be often affected by systemic bias from unknown sources, failing adequately normalize can lead erroneous conclusions. To researchers easily evaluate compare different normalization methods via a user-friendly interface, we have developed "proteiNorm"....
Background The transradial approach (TRA) to endovascular procedures decreases access site morbidity and mortality in comparison with the traditional transfemoral technique (TFA). Despite its improved safety profile, there is a concern that TRA less favorable for neurointerventional require large coaxial systems manage small tortuous cerebral vessels. Objective To report our experience flow diverter placement treatment of unruptured aneurysms. Methods We performed retrospective review...
Phthalates and other endocrine-disruptive chemicals are manufactured in large quantities for use as plasticizers commercial applications, resulting ubiquitous human exposure thus, concern regarding their toxicity. Innate defense against small molecule exposures is controlled part by the constitutive androstane receptor (CAR) pregnane X (PXR). The CAR gene undergoes multiple alternative splicing events CAR2 CAR3 variant receptors. Recent studies from our laboratory show that potently...
When generating monoclonal antibodies (mAb) against small molecules, the chemical composition and molecular orientation of drug-like hapten on antigen is a crucial determinant. This especially important when attempting to discover therapeutic mAb drugs abuse (+)-methamphetamine [(+)-METH], (+)-amphetamine [(+)-AMP], related compound (+)-3,4-methylenedioxymethamphetamine [(+)-MDMA, plus isomer in racemic mixture known as MDMA or ecstasy]. The goal these studies was design synthesize...
Transradial artery access (TRA) for cerebrovascular angiography is increasing due to decreased site complications and overwhelming patient preference. While interventional cardiologists have reported up 10 successive TRA procedures via the same radial site, this first study examining use of repeat in neurointerventional procedures.1 METHODS: We reviewed our prospective institutional database all patients who underwent a transradial procedure between 2015 2019. Index were defined as performed...
This study reports the synthesis of mercapto-hapten (S)-N-(2-(mercaptoethyl)-6-(3-(2-(methylamino)propyl)phenoxy)hexanamide [3, (+)-METH HSMO9] and its use to prepare METH-conjugated vaccines (MCV) from maleimide-activated proteins. MALDI-TOF mass spectrometry analysis MCV synthesized using 3 showed there was a high controllable epitope density on two different carrier In addition, produced substantially greater immunological response in mice than previous METH haptens, monoclonal antibody...
Chronic or excessive (+)-methamphetamine (METH) use often leads to addiction and toxicity critical organs like the brain. With medical treatment as a goal, novel single-chain variable fragment (scFv) against METH was engineered from anti-METH monoclonal antibody mAb6H4 (IgG, κ light chain, <i>K</i><sub>d</sub> = 11 nM) found have similar ligand affinity (<i>K</i><sub>d</sub> 10 specificity mAb6H4. The scFv (scFv6H4) cloned, expressed in yeast, purified, formulated naturally occurring mixture...
The chloroplast signal recognition particle consists of a conserved 54-kDa GTPase and novel 43-kDa chromodomain protein (cpSRP43) that together bind light-harvesting chlorophyll a/b-binding (LHCP) to form soluble targeting complex is subsequently directed the thylakoid membrane. Homology-based modeling cpSRP43 indicates presence two previously identified chromodomains along with third N-terminal chromodomain. Chromodomain deletion constructs were used examine role each in mediating distinct...
In addition to addiction, the repeated use of (+)-methamphetamine [(+)-METH], (+)-amphetamine [(+)-AMP], or (±)-3,4-methylenedioxymethamphetamine ((±)-MDMA, commonly called ecstasy) can lead life-threatening medical problems including cardiovascular injury, severe depression, and psychosis. Currently, there are no specific pharmacotherapies treat these problems. this study, we report design synthesis two haptens, (S)-(+)-3-(9-carboxynonyloxy)methamphetamine (3a, (+)-METH MO10)...
Current guidelines recommend restricting acetaminophen (APAP) use in patients with cirrhosis, but evidence to support that recommendation is lacking. Prior studies focused on pharmacokinetics (PK) of APAP cirrhosis did not rigorously examine clinical outcomes, sensitive biomarkers liver damage, or serum APAP‐protein adducts, which are a specific marker toxic bioactivation. Hence, the goal this pilot study was test effects regularly scheduled dosing well‐defined compensated group compared...
Methamphetamine (METH) abuse is a worldwide threat, without any FDA approved medications. Anti-METH IgGs and single chain fragments (scFvs) have shown efficacy in preclinical studies. Here we report affinity enhancement of an anti-METH scFv for METH its active metabolite amphetamine (AMP), through the introduction point mutations, rationally designed to optimize shape hydrophobicity antibody binding pocket. The was measured using saturation technique. mutant scFv-S93T showed 3.1 fold 26 AMP....
Methamphetamine (METH) is a major drug threat in the United States and worldwide. Monoclonal antibody (mAb) therapy for treating METH abuse showing exciting promise understanding of how mAb structure relates to function will be essential future development these important therapies. We have determined crystal structures high affinity anti-(+)-METH therapeutic single chain fragment (scFv6H4, K(D)= 10 nM) derived from one our candidate complex with (+) stereoisomer another abused drug,...
Background: The management of severe traumatic brain injury (sTBI) patients with and without intact cerebral pressure autoregulation (CPA) varies markedly. Recent studies, analyzing beat-to-beat interactions between intracranial (ICP) systolic blood pressure, or transcranial Doppler velocity changes during a rapid drop in perfusion (CPP), suggest that CPA is disrupted after sTBI. We use computed tomography (CTP) to guide manipulation sTBI have found results differ this literature. present...
Treatments specific to the medical problems caused by methamphetamine (METH) abuse are greatly needed. Toward this goal, we developing new multivalent anti-METH antibody fragment-nanoparticle conjugates with customizable pharmacokinetic properties. We have designed a novel single chain fragment an engineered terminal cysteine (scFv6H4Cys). Generation 3 (G3) polyamidoamine dendrimer nanoparticles were chosen for conjugation due their monodisperse properties and multiple amine functional...
To address the need for effective medications to aid in treatment of methamphetamine (METH) abuse, we used a nanotechnology approach customize vivo behavior an anti-METH single chain antibody (scFv7F9Cys). Anti-METH scFv7F9Cys was conjugated dendrimer nanoparticles via polyethylene glycol (PEG) linker generate high-order conjugates termed dendribodies. We found that high affinity (KD = 6.2 nM) and specificity METH unchanged after nanoparticle conjugation. The dendribodies were administered...
Immunotherapy for treating illicit drug abuse is a rapidly advancing field. There are currently two major approaches to developing drug-specific immunotherapies: active and passive. Active immunotherapy involves conjugating drug-like hapten carrier protein using traditional immunization generate immune response in the patient. In contrast, passive utilizes preformed monoclonal antibodies. Whether generated by or delivered passively, antibodies act as pharmacokinetic antagonists binding...
Introduction: An active metabolite of buprenorphine (BUP), called norbuprenorphine (NorBUP), is implicated in neonatal opioid withdrawal syndrome when BUP taken during pregnancy. Therefore, reducing or eliminating metabolism to NorBUP a novel strategy that will likely lower total fetal exposure opioids and thus improve offspring outcomes. Precision deuteration alters pharmacokinetics drugs without altering pharmacodynamics. Here, we report the synthesis testing deuterated (BUP-D2). Methods:...