Biomedical subjects

Tian Huai Shen

Publications and source records attributed to Tian Huai Shen.

3 recordsLinked to original sources

PubMed2026

Inherited Susceptibility to Urinary Tract Infections from Kidney Papilla to Bladder.

Urinary tract infections (UTIs) are traditionally viewed as environmentally driven, yet their inherited susceptibility remains largely unexplored. We conducted a cross-biobank genome-wide association study of recurrent UTIs in 1,860,836 individuals (213,869 cases and 1,646,967 controls). We identified 36 genetic susceptibility loci and performed tissue-based multi-omic mapping to prioritize candidate causal genes. UTI risk alleles preferentially modulated epithelial gene expression in kidney and bladder, converging on urinary epithelia structure and function. PSCA, encoding a secreted epithelial surface protein, emerged as the strongest candidate under genetic control; the gene product is constitutively secreted into the urine from kidney papilla and bladder epithelia, binds uropathogenic E. coli, and inhibits bacterial growth in vitro. Our findings define the polygenic architecture of UTIs and highlight the critical role of uroepithelial surface defenses, providing a new framework for host-directed, non-antibiotic interventions.

Journal Article↗

PubMed2026

A posttranslational modification of fimbriae drives pathogenicity in Klebsiella pneumoniae.

Antimicrobial resistance is a severe public health burden. Especially concerning are multidrug resistant (MDR) infections, which restrict treatment options and significantly increase mortality risk. A major cause of MDR infections worldwide is carbapenem-resistant Klebsiella pneumoniae (CRKp). The predominant CRKp sequence type worldwide is ST258. However, the factors underlying ST258's epidemic success are not well defined. Genomic analyses of clinical isolates of CRKp have found that the two-component regulatory system CrrAB is a genomic feature of ST258, suggesting that it may contribute to its global dominance. Despite this, the molecular details underpinning CrrAB's contribution to ST258 Kp biology and pathogenicity are poorly understood. We used RNA-sequencing to identify the regulon of CrrA and found that CrrAB induces the expression of a gene, encoding Crr-regulated fimbriae modifying protein (CfmP), that is essential for pathogenesis driven by this two-component system. We performed mass spectrometry analyses of fimbriae purified from Kp expressing or lacking cfmP and found that CfmP induces a novel oxidation to a histidine residue in the major pilin subunit of fimbriae, FimA. We demonstrate that this oxidation significantly increases host cell adhesion and high bacterial loads within the host. CrrAB also drives high antibiotic resistance in CRKp. Thus, our results place CrrAB at the intersection of pathogenicity and antibiotic resistance supporting its function as an important regulatory system driving the global dominance of ST258.

Klebsiella pneumoniae↗

PubMed2006

The mechanisms of PML-nuclear body formation.

PML nuclear bodies (NBs) are nuclear structures that have been implicated in processes such as transcriptional regulation, genome stability, response to viral infection, apoptosis, and tumor suppression. PML has been found to be essential for the formation of the NBs, as these structures do not form in Pml null cells, although PML add back fully rescues their formation. However, the basis for such a structural role of PML is unknown. We demonstrate that PML contains a SUMO binding motif that is independent of its SUMOylation sites and is surprisingly necessary for PML-NB formation. We demonstrate that the PML RING domain is critical for PML SUMOylation and PML-NB formation. We propose a model for PML-NB formation whereby PML SUMOylation and noncovalent binding of PML to SUMOylated PML through the SUMO binding motif constitutes the nucleation event for subsequent recruitment of SUMOylated proteins and/or proteins containing SUMO binding motifs to the PML NBs.

Amino Acid Motifs↗