A5090877570- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Glycosylation and Glycoproteins Research
- Liver physiology and pathology
- Escherichia coli research studies
- PI3K/AKT/mTOR signaling in cancer
- T-cell and B-cell Immunology
- Reproductive tract infections research
- Advanced biosensing and bioanalysis techniques
- vaccines and immunoinformatics approaches
- Urinary Tract Infections Management
- DNA Repair Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Supramolecular Self-Assembly in Materials
- DNA and Nucleic Acid Chemistry
- Carbohydrate Chemistry and Synthesis
- Metal complexes synthesis and properties
- Enterobacteriaceae and Cronobacter Research
Washington University in St. Louis
2015-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2022
Massachusetts Institute of Technology
2019-2021
University of Wisconsin–Madison
2019
IIT@MIT
2019
Alvin J. Siteman Cancer Center
2015
Abstract Uropathogenic E. coli (UPEC) employ the mannose‐binding adhesin FimH to colonize bladder epithelium during urinary tract infection (UTI). Previously reported antagonists exhibit good potency and efficacy, but low bioavailability a short half‐life in vivo. In rational design strategy, we obtained an X‐ray structure of lead mannosides then designed with improved drug‐like properties. We show that cyclizing carboxamide onto biphenyl B‐ring aglycone into fused heterocyclic ring,...
Dendritic cells (DCs) are highly effective antigen-presenting that shape immune responses. Vaccines deliver antigen to the DCs can harness their power. DC surface lectins recognize glycans not typically present on host tissue facilitate uptake and presentation. target these should offer improved delivery, but efficacy will depend how lectin targeting influences T cell subtypes result. We examined structure signaling from C-type DC-SIGN (dendritic cell-specific intercellular adhesion...
Significance Dendritic cells (DCs) express cell-surface lectins that bind to carbohydrates displayed on the surface of pathogens. The binding pathogens these results in internalization endosomal compartments, where are destroyed and an immune response is initiated. HIV-1 can subvert this process—lectin engagement routes cellular compartments allow virus evade destruction. We synthesized glycopolymers test whether size physical properties antigens impact trafficking. Small polymers trafficked...
Carbohydrate-binding proteins (lectins) play vital roles in cell recognition and signaling, including pathogen binding innate immunity. Thus, targeting lectins, especially those on the surface of immune cells, could advance immunology drug discovery. Lectins are typically oligomeric; therefore, many most potent ligands multivalent. An effective strategy for lectin is to display multiple copies a single glycan epitope polymer backbone; however, drawback such multivalent they cannot...
Subunit vaccines can have excellent safety profiles, but their ability to give rise robust immune responses is often compromised. For glycan-based vaccines, insufficient understanding of B and T cell epitope combinations that yield optimal activation hinders optimization. To determine which antigen features promote desired IgG responses, we synthesized epitope-functionalized polymers using ring-opening metathesis polymerization (ROMP) assessed the effect loading. The most were induced by...
Abstract The DNA excision repair protein ERCC1 and the damage sensor protein, XPA are highly overexpressed in patient samples of cisplatin‐resistant solid tumors including lung, bladder, ovarian, testicular cancer. cisplatin‐DNA crosslinks is dependent upon nucleotide (NER) that modulated by protein‐protein binding interactions ERCC1, endonuclease, XPF, XPA. Thus, inhibition their function a potential therapeutic strategy for selective sensitization to DNA‐damaging platinum‐based cancer...
Abstract Dendritic cell (DC) lectins mediate the recognition, uptake, and processing of antigens, but they can also be co-opted by pathogens for infection. These distinct activities depend upon routing antigens within cell. Antigens directed to endosomal compartments are degraded peptides presented on MHC class II molecules thereby promoting immunity. Alternatively, HIV-1 avoid degradation, as virus engagement with C-type lectin receptors (CLRs), such DC-SIGN, results in trafficking...