Biology subjects

Kang, T. K.

Publications and source records attributed to Kang, T. K..

3 recordsLinked to original sources

bioRxiv2025

HIV Virion Capturing Liposomes for Therapeutic Vaccination

HIV infection currently has no effective cures and requires lifelong antiretroviral treatments. Cures have failed due to HIVs immune evasion and rapid mutation rate. Here we present a first in class HIV therapeutic vaccine, termed nanotrap therapeutic vaccines (NTVs) that are designed to capture circulating HIV virions and facilitate internalization by local antigen presenting cells. NTVs are modified liposomes that display the CD4 mimetic molecule, CJF-III-288, on their surfaces and have the TLR 7/8 agonist R848 loaded into their core. We show that NTVs can 1) bind gp120 and capture pseudoviral particles, 2) facilitate uptake by antigen presenting cells and 3) generate robust anti-HIV CD8 T cell immunity in transient infection mouse models. NTVs have translational potential to generate patient-specific HIV immunity.

bioengineering↗

bioRxiv2025

Cinnamomum cassia Extract and Its Novel Isolated Compound Suppress Inflammation via Autophagy Induction in Sepsis

Uncontrolled inflammation is central to the development of diseases such as sepsis, and autophagy has emerged as a critical regulatory mechanism in this process. The ethanol extract of Cinnamomum cassia (EECC) was identified as a potent autophagy inducer through high-throughput LC3 reporter screening. EECC enhanced autophagic flux, as confirmed by RFP-GFP-LC3 imaging and immunoblotting. It also suppressed Toll-like receptor signaling and reduced pro-inflammatory cytokine production in macrophages. EECC inhibited nuclear factor-{kappa}B signaling in an autophagy-dependent manner, as this effect was reversed by autophagy inhibitors. To identify active constituents, 24 compounds were isolated from EECC, including six novel structures. Among the novel compounds, Cassitamine F exhibited dual activity as an autophagy inducer and inflammation suppressor. In a lipopolysaccharide-induced sepsis model, Cassitamine F significantly reduced serum levels of pro-inflammatory cytokines. These findings suggest that EECC and Cassitamine F may hold therapeutic potential for autophagy-targeted treatment of sepsis and other inflammation-related disorders. Highlights- Ethanol extract of Cinnamomum cassia (EECC) identified as a potent autophagy inducer via high-throughput LC3 HiBiT screening. - EECC suppresses Toll-like receptor signaling and pro-inflammatory cytokines through autophagy-dependent pathways. - Twenty-four compounds were isolated from EECC, including six novel structures (Cassitamine A-F). - Cassitamine F exhibits dual activity: induction of autophagy and inhibition of inflammation. - Cassitamine F significantly reduces serum cytokine levels in an LPS-induced sepsis model, suggesting therapeutic potential.

pharmacology and toxicology↗

bioRxiv2024

Massively parallel screening of TIR-derived peptides reveals vast TLR-targeting immunomodulatory peptides

Toll-like receptors (TLRs) are critical regulators of the immune system, and altered TLR responses lead to a variety of inflammatory diseases. Interference of intracellular TLR signaling, which is mediated by multiple Toll/interleukin-1 receptor (TIR) domains on all TLRs and TLR adapters, is an effective therapeutic strategy against immune dysregulation. Peptides that inhibit TIR-TIR interactions by fragmenting interface residues have potential as therapeutic decoys. However, a systematic method for discovering TIR-targeting moieties has been elusive, limiting exploration of the vast unsequenced space of the TIR domain family. Here, we developed a comprehensive parallel screening method to uncover novel TIR-binding peptides derived from previously unexplored surfaces on a wide range of TIR domains. We constructed a large peptide library, named TIR surfacesome, by tiling surface sequences of the large TIR domain family and screening against MALTIR and MyD88TIR, TIRs of two major TLR adaptor proteins, resulting in the discovery of hundreds of TIR-binding peptides. The selected peptides inhibited TLR signaling, demonstrated anti-inflammatory effects in macrophages and therapeutic potential in mouse inflammatory models. This approach may facilitate the development of TLR-targeted therapeutics.

molecular biology↗