Biology subjects

Sung, C.-H.

Publications and source records attributed to Sung, C.-H..

3 recordsLinked to original sources

bioRxiv2026

Eastern equine encephalitis virus-vaccinated mice are protected against Madariaga virus despite negligible neutralizing antibody titers

Madariaga virus (MADV) is an understudied member of the eastern equine encephalitis virus (EEEV) complex that circulates widely in Latin America and may be geographically expanding. Spillover infections can cause severe disease in humans and equids. Despite these public and animal health concerns, no MADV vaccines or treatments are available. In this context, commercially available equine vaccines against the closely related North American EEEV (NA EEEV) could potentially provide heterologous protection against MADV. However, previous studies have shown weak or undetectable MADV-neutralizing antibody responses in equids and humans immunized with inactivated NA EEEV vaccines, and whether protection can occur despite these limited neutralizing antibody responses remains unknown. We evaluated a commercial equine trivalent inactivated NA EEEV vaccine against MADV challenge in NIH Swiss mice. Animals received two vaccine doses 14 days apart and were challenged 14 days later. Vaccination provided protection against lethal disease, whereas 36% mortality occurred in the unvaccinated group. Overall, vaccinated animals developed fewer and less severe clinical signs. MADV RNAemia was not detected following vaccination, and tissue dissemination was significantly reduced compared with the unvaccinated group. Central nervous system lesions were observed only in the unvaccinated group. Despite protection, most vaccinated mice had no detectable MADV-neutralizing antibody titers, and those that seroconverted developed only low titers, whereas most unvaccinated mice developed intermediate to high titers. These findings demonstrate that an inactivated NA EEEV-containing vaccine can protect against severe MADV disease despite limited MADV-neutralizing antibody responses.

systems biology↗

bioRxiv2026

An Integrated Multi-omics Single Cell Atlas of the Human RPE and Choroid

The retinal pigment epithelium and choroid are critical for supporting the function and maintaining the homeostasis of the outer retina, and their dysfunction underlies a range of inherited and complex ocular diseases. To comprehensively characterize the cellular, transcriptomic, and epigenomic heterogeneity and dynamics within these tissues, we assembled an integrated multi-omics reference atlas comprising 719,813 single-cell/single-nucleus transcriptomes and 234,007 snATAC-seq profiles from 102 ancestrally diverse donors spanning 0 to 99 years of age, including cells from both the macula and periphery. This atlas resolves 48 distinct cell types or states and catalogs 448,567 open chromatin regions. Specifically, we resolved five distinct RPE subpopulations organized along a central-to-peripheral spatial axis, alongside two distinct stress/senescence states. We reconstructed the transcriptomic and epigenetic zonation of endothelial cells and expanded choroidal stromal heterogeneity by characterizing 11 fibroblast and two pericyte types. Age-associated compositional analysis revealed a significant fractional depletion of melanocytes, PI16+ fibroblasts, and venule endothelial cells with age, alongside a modest relative loss of central RPE and a corresponding increase in far-peripheral RPE. Cell-type-specific aging transcriptomics uncovered shared pathways related to inflammatory responses alongside distinct cell-type-specific signatures. Notably, significant age-associated epigenetic changes concentrated in the macula during the transition from early-to-middle adulthood and remained stable into old age, with transcription factors from the AP-1/bZIP family emerging as the dominant enriched motifs. Finally, integrating this atlas with AMD GWAS data provides novel variant-to-gene evidence implicating LIPG and COL4A3 in AMD pathogenesis. Together, this multi-omics atlas serves as both an invaluable community reference and a powerful discovery engine that translates genetic risk signals into localized target cells and candidate mechanisms, laying a foundation for understanding RPE/choroid biology in health and disease.

genomics↗

bioRxiv2021

Short- and long-term effects of amoxicillin/clavulanic acid or doxycycline on the gastrointestinal microbiome of growing cats

Antibiotic treatment in early life influences gastrointestinal (GI) microbial composition and function. In humans, the resultant intestinal dysbiosis is associated with an increased risk for certain diseases later in life. The objective of this study was to determine the temporal effects of antibiotic treatment on the GI microbiome of young cats. Fecal samples were collected from cats randomly allocated to receive either amoxicillin/clavulanic acid (20 mg/kg q12h) for 20 days (AMC group; 15 cats) or doxycycline (10 mg/kg q24h) for 28 days (DOX group;15 cats) as part of the standard treatment of upper respiratory tract infection. In addition, feces were collected from healthy control cats (CON group;15 cats). All cats were approximately two months of age at enrolment. Samples were collected on days 0 (baseline), 20 or 28 (AMC and DOX, respectively; last day of treatment), 60, 120, and 300. DNA was extracted and sequencing of the 16S rRNA gene and qPCR assays were performed. Fecal microbial composition was different on the last day of treatment for AMC cats, and 1 month after the end of antibiotic treatment for DOX cats, compared to CON cats. Species richness was significantly greater in DOX cats compared to CON cats on the last day of treatment. Abundance of Enterobacteriales was increased, and that of Erysipelotrichi was decreased in cats of the AMC group on the last day of treatment compared to CON cats. The abundance of the phylum Proteobacteria was increased in cats of the DOX group on days 60 and 120 compared to cats of the CON group. Only minor differences in abundances between the treatment groups and the control group were present on day 300. Both antibiotics appear to delay the developmental progression of the microbiome, and this effect is more profound during treatment with amoxicillin/clavulanic acid and one month after treatment with doxycycline. Future studies are required to determine if these changes influence microbiome function and whether they have possible effects on disease susceptibility in cats.

microbiology↗