A5057272391- Gut microbiota and health
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Hematopoietic Stem Cell Transplantation
- Metal complexes synthesis and properties
- Probiotics and Fermented Foods
- Tryptophan and brain disorders
- RNA and protein synthesis mechanisms
- Infant Health and Development
- Glioma Diagnosis and Treatment
- X-ray Diffraction in Crystallography
- Biochemical Analysis and Sensing Techniques
- Crystallography and molecular interactions
- Neutropenia and Cancer Infections
- Crystallization and Solubility Studies
- Digestive system and related health
- RNA Interference and Gene Delivery
- Pediatric health and respiratory diseases
- Gene expression and cancer classification
- Gastrointestinal motility and disorders
- Ferrocene Chemistry and Applications
- Clostridium difficile and Clostridium perfringens research
- Cancer-related gene regulation
- Vagus Nerve Stimulation Research
- Chemotherapy-induced cardiotoxicity and mitigation
Wake Forest University
2011-2022
Memorial Sloan Kettering Cancer Center
2017-2020
Icahn School of Medicine at Mount Sinai
2016-2020
University Hospital Regensburg
2020
Mary Lyon Centre at MRC Harwell
2015
Medical Research Council
2015
Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence enterococcal expansion, which was associated with graft-versus-host disease (GVHD) mortality. We found
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Despite evidence linking the human microbiome to health and disease, how microbiota affects physiology remains largely unknown. Microbiota-encoded metabolites are expected play an integral role in health. Therefore, assigning function these is critical understanding complex interactions developing microbiota-inspired therapies. Here, we use large-scale functional screening of molecules produced by individual members a simplified identify bacterial that agonize G-protein-coupled receptors...
Background: Tranexamic acid (TXA) is an antifibrinolytic drug. Topical administration of TXA during total knee arthroplasty (TKA) favored for certain patients because concerns about thrombotic complications, despite a lack supporting literature. We compared local and systemic levels thrombogenic markers, interleukin (IL)-6, between who received intravenous (IV) those topical TXA. Methods: Seventy-six scheduled TKA were enrolled in this randomized double-blinded study. The IV group 1.0 g...
Abstract Platinum–acridine hybrid agents show low‐nanomolar potency in chemoresistant non‐small cell lung cancer (NSCLC), but high systemic toxicity vivo. To reduce the promiscuous genotoxicity of these and improve their pharmacological properties, a modular build–click–screen approach was used to evaluate small library twenty containing truncated extended chromophores varying basicities. Selected derivatives were resynthesized tested five NSCLC lines representing large cell, squamous...
Abstract Kinase inhibitors (KIs) represent an important class of anti-cancer drugs. Although cardiotoxicity is a serious adverse event associated with several KIs, the reasons remain poorly understood, and its prediction remains challenging. We obtain transcriptional profiles human heart-derived primary cardiomyocyte like cell lines treated panel 26 FDA-approved KIs classify their effects on subcellular pathways processes. Individual patient reports for these obtained from FDA Adverse Event...
A combination of biophysical, biochemical, and computational techniques was used to delineate mechanistic differences between the platinum–acridine hybrid agent [PtCl(en)(L)](NO3)2 (complex 1, en = ethane-1,2-diamine, L 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) a considerably more potent second-generation analogue containing L′ N-[2-(acridin-9-ylamino)ethyl]-N-methylpropionamidine 2). Calculations at density functional theory level provide rationale for binding preference both...
Abstract Using a versatile synthetic approach, new class of potential ester prodrugs highly potent, but systemically too toxic, platinum–acridine anticancer agents was generated. The hybrids contain hydroxyl group, which has been masked with cleavable lipophilic acyl moiety. Both butanoic (butyric) and bulkier 2‐propanepentanoic (valproic) esters were introduced. goals this design to improve the drug‐like properties (e.g., log D ) reduce systemic toxicity pharmacophore. Two distinct pathways...
Thiourea-modified 3-chloro-4-fluoroanilino-quinazoline derivatives have been studied as potential receptor-targeted carrier ligands in linear gold(I) complexes. The molecules mimic the epidermal growth factor receptor (EGFR) tyrosine kinase-targeted inhibitor gefitinib. Thiourea groups were either directly attached to quinazoline-C6 (compounds 4, 5, and 7) or linked this position via a flexible ethylamino chain (compound 9). Compound 7 acts thiourea-S/quinazoline-N1 mixed-donor ligand,...
DNA G-quadruplexes in human telomeres and gene promoters are being extensively studied for their role controlling the growth of cancer cells. have been unambiguously shown to exist both vitro vivo, including guanine (G)-rich genes encoding pre-ribosomal RNA (pre-rRNA), which is transcribed cell's nucleolus. Recent studies strongly suggest that these sequences ("rDNA"), rRNA, a potential anticancer target through inhibition polymerase I (Pol I) ribosome biogenesis, but structures ribosomal at...
The prevalence of mutant IDH1 brain tumors has generated significant efforts to understand the role mutated enzyme product D-2-hydroxyglutarate (D2HG), an oncometabolite, in tumorigenesis, as well means eliminate it. Glymphatic clearance was proposed a pathway that could be manipulated accelerate D2HG and dictated study design consisted two cohorts mice bearing U87/mutant intracerebral who underwent microdialysis – providing interstitial fluid concentrations - sampling periods awake asleep...
Bone-marrow transplantation (BMT) offers curative potential for patients with high-risk hematologic malignancies. However, the post-transplantation period is characterized by immunodeficiency and delayed immune reconstitution an important contributor to transplant-related morbidity mortality (Maury et al., Br J Haematol, 2001; Small Blood, 1999). Recent studies indicate that intestinal microbiota not only regulates mucosal immunity, but can also contribute systemic immunity hematopoiesis...
Abstract Review: 92 refs.
Abstract Despite evidence linking the human microbiome to health and disease, mechanistic details of how microbiota affects physiology remain largely unknown. Metabolites encoded by bacteria are expected play an integral role in microbiota’s effect on its host. Assigning function these metabolites is therefore critical determining molecular underpinnings host-microbe relationship ultimately developing inspired therapies. Here we use large-scale functional screening small molecules produced...