Biomedical subjects

Chunling Hu

Publications and source records attributed to Chunling Hu.

5 recordsLinked to original sources

PubMed2025

Genomic and Immune Landscape of Pancreatic Ductal Adenocarcinoma Associated with Germline Pathogenic Variants in ATM.

PURPOSE: Germline pathogenic variants (PV) in ATM increase the risk of pancreatic ductal adenocarcinoma (PDAC), but the underlying tumor biology of PDAC associated with germline PV in ATM has not been adequately explored. EXPERIMENTAL DESIGN: Whole-genome, whole-exome, and RNA sequencing were performed on PDAC tumors from 25 germline ATM PV carriers diagnosed at Mayo Clinic between 2007 and 2017. Somatic and copy-number alterations, mutational signatures, transcriptomic subtypes, and the immune landscape were evaluated. RESULTS: High-quality whole-exome and whole-genome sequencing were obtained from 21 and 15 tumors, respectively. Biallelic inactivation of ATM was observed in 87%, KRAS PV in 90%, CDKN2A homozygous loss in 60%, and TP53 alterations in <10% of these tumors. A predominant clock-like mutational signature was present in all samples. Whole-transcriptome analysis identified that the aberrantly differentiated endocrine exocrine subtype accounted for 18% of PDAC and was consistently associated with >5-year overall survival. In addition, a 28-gene expression-based signature associated with overall survival was identified and further validated in The Cancer Genome Atlas cohort. Immune landscape analysis through CODEX identified enriched CD4 T-helper cell/tumor interactions and reduced B7H3-high cell/tumor interactions in ATM PV carriers compared with noncarriers. CONCLUSIONS: The observed absence of TP53 PV and enrichment for CDKN2A alterations in ATM tumors, along with differences in the mutational signatures, transcriptomic subtypes and immune landscape, improve our understanding of the mechanistic pathways involved in PDAC development in germline ATM PV carriers and help identify potential targeted therapeutic strategies.

Humans↗

PubMed2025

Asthma causally affects the brain cortical structure: a Mendelian randomization study.

OBJECTIVE: The potential causal relationship between asthma and brain structures remains uncertain. We performed a two-sample Mendelian randomization to investigate the causal effects of various asthma phenotypes - unspecified asthma, moderate-to-severe asthma, childhood-onset asthma, and adult-onset asthma (AOA) - on cerebral cortex structure. METHODS: We utilized phenotype data derived from genome-wide association studies (GWASs). The ENIGMA Consortium GWAS provided outcome variables for surface area (SA) and thickness across the whole brain and 34 region-specific areas of the cerebral cortex. Using the inverse variance-weighted method as our primary estimation approach, we employed several techniques, including Cochran's Q statistic, the MR-PRESSO global test, MR-Egger, and weighted median, to assess heterogeneity and pleiotropy, thereby ensuring the robustness of our findings. Additionally, we conducted enrichment analyses of gene sets with causal effects on cortical structure and applied bioinformatics techniques to construct interaction networks and identify hub nodes. RESULTS: At the global level, AOA was associated with a significant reduction in full cortical SA (β = -58.49 mm2, p = 0.017). In regional analyses, moderate-to-severe asthma exhibited a more pronounced impact on the cerebral cortex compared to other phenotypes. Enrichment analysis revealed that pathways implicated in brain morphology among asthma patients were primarily linked to immune and inflammation-driven pathways. CONCLUSIONS: Our findings provide new evidence supporting a causal relationship between asthma and alterations in cortical structure, offering potential explanations for cognitive and psychiatric impairments observed in individual post-asthma.

Humans↗

PubMed2006

Identification of amino acid residues involved in the interaction between measles virus Haemagglutin (MVH) and its human cell receptor (signaling lymphocyte activation molecule, SLAM).

Signaling lymphocyte activation molecule (SLAM; also known as CD150) is a newly identified cellular receptor for measles virus (MV). The interaction between MV Haemagglutin (MVH) and SLAM is an initial step for MV entry. We have identified several novel SLAM binding sites at residues S429, T436 and H437 of MVH protein and MVH mutants in these residues dramatically decrease the ability to interaction with the cell surface SLAM and fail to coprecipitation with SLAM in vivo as well as malfunction in syncytium formation. At the same time, K58, S59 and H61 of SLAM was also identified to be critical for MVH and SLAM binding. Further, these residues may be useful targets for the development of measles therapy.

Animals↗

PubMed2004

Is mRNA and protein level of CD46 altered in measles virus vaccine strain S191-infected cells?

Previous research showed that the expression of measles virus receptor CD46 was downregulated after expression of measles virus hemagglutinin protein on the surface of the virus infected cell or triggered by infected cell-to-cell contact. We reported here that the mRNA level of CD46 in MV infected cells was not changed which was tested by real-time quantitative PCR. To further analyse the surface expression alteration of CD46 after MV infection, flow cytometric analysis and indirect immunofluorescence were used to detect the protein level of CD46. Altogether, our results provided a demonstration that the expression of CD46 was not downregulated by the infection of MV strain S191 both on mRNA level and cellular surface protein level. Previous results reported that the "downregulation" of CD46 expression on the cell surface may take place because H protein masks the antibody recognition site on CD46 which results in "downregulation" of the expression of CD46.

Animals↗

PubMed2004

Characterization of a region involved in binding of measles virus H protein and its receptor SLAM (CD150).

Signaling lymphocyte activation molecule (SLAM; also known as CD150) is a newly identified cellular receptor for measles virus (MV). MV Hemagglutinin protein (H) mediates MV entry into host cells by specifically binding to SLAM. Amino acid 27-135 of SLAM was previously shown to be the functional domain to interact with H and used to screen a 10-mer phage display peptide library in this study. After four rounds of screening and sequence analysis, the deduced amino acid sequence of screened peptides SGFDPLITHA and SDWDPLFTHK showed to be highly homologous with amino acid 429-438 of MV H (SGFGPLITHG). Peptides SGFDPLITHA and SDWDPLFTHK specifically inhibited binding of H to SLAM and further inhibition of MV infection suggests that these peptides can be developed to MV blocking reagents and amino acid 429-438 in H protein is functionally involved in receptor binding and may constitute part of the receptor-binding determinants on H protein.

Animals↗