A5024191669- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Cancer therapeutics and mechanisms
- Alzheimer's disease research and treatments
- Nanoplatforms for cancer theranostics
- Receptor Mechanisms and Signaling
- Cancer Research and Treatments
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Radiopharmaceutical Chemistry and Applications
- CAR-T cell therapy research
- Computational Drug Discovery Methods
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Lung Cancer Research Studies
- Memory and Neural Mechanisms
- Protein Degradation and Inhibitors
- Pharmacological Receptor Mechanisms and Effects
- DNA and Nucleic Acid Chemistry
- Drug Transport and Resistance Mechanisms
- Education, Achievement, and Giftedness
- Bird parasitology and diseases
- Names, Identity, and Discrimination Research
- Neurogenetic and Muscular Disorders Research
- Neural and Behavioral Psychology Studies
Tallahassee Orthopedic Clinic
2024
Melinta Therapeutics (United States)
2022-2023
Bristol-Myers Squibb (United States)
2006-2022
Poultry Research Institute
2015
Bristol-Myers Squibb (Germany)
2008
University of Alabama at Birmingham
2006
While specific cell signaling pathway inhibitors have yielded great success in oncology, directly triggering cancer death is one of the drug discovery challenges facing biomedical research era precision oncology. Attempts to eradicate cells expressing unique target proteins, such as antibody-drug conjugates (ADCs), T-cell engaging therapies, and radiopharmaceuticals been successful clinic, but they are limited by number targets given inability intracellular proteins. More recently,...
Antisense oligonucleotides are a relatively new therapeutic modality and safety evaluation is still developing area of research. We have observed that some can produce acute, nonhybridization dependent, neurobehavioral side effects after intracerebroventricular (ICV) dosing in mice. In this study, we use combination vitro, vivo, bioinformatics approaches to identify sequence design algorithm, which reduce the number acutely toxic molecules synthesized tested find cellular assay measuring...
Abstract Exatecan and deruxtecan are antineoplastic camptothecin derivatives in development as tumor-targeted-delivery warheads various formulations including peptides, liposomes, polyethylene glycol nanoparticles, antibody–drug conjugates. Here, we report the molecular pharmacology of exatecan compared with clinically approved topoisomerase I (TOP1) inhibitors preclinical models for validating biomarkers combination ataxia telangiectasia Rad3-related kinase (ATR) inhibitors. Modeling...
Abstract Both K‐12 schools and STEM disciplines are embedded in White supremacy exclusion, making it that much harder for Black women to maintain an interest sense of belonging STEM. Through a Critical Race Feminism methodology, we tell the counterstories our two co‐authors, women, over course their lives. these (stories run counter normative stories as male White), Kelli Samantha show us how they negotiated maintained even through moments self‐doubt trajectory. These negotiations allowed...
The development of alpha7 nicotinic acetylcholine receptor agonists is considered a promising approach for the treatment cognitive symptoms in schizophrenia patients. In present studies we characterized novel agent, (2R)-N-(6-(1H-imidazol-1-yl)-4-pyrimidinyl)-4'H-spiro[4-azabicyclo[2.2.2]octane-2,5'-[1,3]oxazol]-2'-amine (BMS-933043), vitro and rodent models schizophrenia-like deficits cognition sensory processing. BMS-933043 showed potent binding affinity to native rat (Ki = 3.3 nM)...
Positive allosteric modulators (PAMs) of the metabotropic glutamate receptor subtype 5 (mGluR5) are interest due to their potential therapeutic utility in schizophrenia and other cognitive disorders. Herein we describe discovery optimization a novel oxazolidinone-based chemotype identify BMS-955829 (4), compound with high functional PAM potency, excellent mGluR5 binding affinity, low fold shift, selectivity for subtype. The shift absence agonist activity proved critical identification...
Topoisomerase inhibitors are potent DNA damaging agents which widely used in oncology, and they demonstrate robust synergistic tumor cell killing combination with repair inhibitors, including poly(ADP)-ribose polymerase (PARP) inhibitors. However, their use has been severely limited by the inability to achieve a favorable therapeutic index due severe systemic toxicities. Antibody-drug conjugates address this issue via antigen-dependent targeting delivery of payloads, but approach requires...
Tau is a microtubule-associated protein (MAPT, tau) implicated in the pathogenesis of tauopathies, spectrum neurodegenerative disorders characterized by accumulation hyperphosphorylated, aggregated tau. Because tau pathology can be distinct across diseases, pragmatic therapeutic approach may to intervene at level transcript, as it makes no assumptions mechanisms toxicity. Here we performed large library screen locked-nucleic-acid (LNA)-modified antisense oligonucleotides (ASOs), where...
Alzheimer's disease (AD) is a progressive neurodegenerative disease. Amyloid beta (Abeta) peptides are hypothesized to cause the initiation and progression of AD based on pathologic data from patients, genetic analysis mutations that early onset forms AD, preclinical studies. Based this hypothesis, beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) inhibitors an attractive therapeutic approach for because cleavage APP by BACE1 required form Abeta. In study, three potent...
The design and synthesis of a series quinuclidine-containing spirooxazolidines ("spiroimidates") their utility as α7 nicotinic acetylcholine receptor partial agonists are described. Selected members the demonstrated excellent selectivity for over highly homologous 5-HT3A receptor. Modification N-spiroimidate heterocycle substituent led to (1S,2R,4S)-N-isoquinolin-3-yl)-4'H-4-azaspiro[bicyclo[2.2.2]octane-2,5'oxazol]-2'-amine (BMS-902483), potent agonist, which improved cognition in...
Aims: To determine whether antigen-independent targeting of the TOP1 inhibitor exatecan to tumor with a pH-sensitive peptide (CBX-12) produces superior synergy immunotherapy compared unconjugated exatecan. Materials & methods: In vitro and ex vivo functional assays were performed via FACS ELISA assays. efficacy was evaluated in syngeneic CT26 model. Results: CBX-12 combined anti-PD-1 or anti-CTLA4 results delayed growth complete response, cured animals displaying long-term antitumor...
Abstract Background: Novel drugs are needed to tackle forms of prostate cancer that demonstrate resistance hormonal agents. Halda has invented an innovative treatment approach does not rely on oncogenic drivers. Regulated Induced Proximity Targeting Chimera (RIPTAC™) therapeutics heterobifunctional small molecules work via a hold and kill mechanism the potential overcome drug mechanisms. RIPTAC function by holding together two proteins, cancer-specific protein, protein with essential (EP) in...
Abstract Topoisomerase inhibitors are potent DNA damaging agents with great potential as anti-cancer drugs for a wide range of solid tumors. However, dose-limiting toxicities such myelosuppression and gastric toxicity have prevented them from reaching their full clinical potential. Targeting topoisomerase antibodies (i.e. antibody-drug conjugates; ADCs) may enhance the therapeutic window these agents, but this approach typically limits applicability to small subset patients tumors expressing...
Alzheimer's disease (AD) is a progressive neurodegenerative disease. Aβ peptides are hypothesized to cause the initiation and progression of AD based on pathologic data from patients, genetic analysis mutations that early onset forms AD, preclinical studies. Based this hypothesis, BACE1 inhibitors an attractive therapeutic approach for since cleavage amyloid precursor protein (APP) by required form Aβ. Three potent characterized in both vitro vivo models. All three decrease formation...
In this field experiment, a confederate asked participants to provide quarter for the make telephone call. experimental condition, based on concept of exchange, offered twenty-five pennies quarter. The researchers found that there was significant difference in whether or not pennies. Eighty-five percent complied when pennies, while only 35 without offer exchange. Gender factor. Participants over sixty-years-old more often than any other age group. Economic status factor those middle range...
Hen diuresis syndrome has emerged over the past 5 yr as a significant cause of mortality in U.S. broiler breeder industry. The condition affects hens production and is characterized by transient muscle weakness vent region, diuresis, often urate deposits on skin below vent. Affected are seen straining to lay an egg, which suggests oviduct contraction also impaired. Related hen mortality, reaching 1% or more week, believed be primarily result male aggression region (Turner et al.,...
Supplementary Figure from TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor
Supplementary Figure from TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor
Supplementary Figure from TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor
Supplementary Figure from TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor