Biology subjects

Yim, S.

Publications and source records attributed to Yim, S..

3 recordsLinked to original sources

bioRxiv2026

EFFECTS OF SUBCHRONIC EXPOSURE TO POLYSTYRENE NANOPLASTICS ON THE MOUSE INTESTINE

Nanoplastics (NPs) are being used increasingly in cosmetics, personal care products, foods, automotive products, and cleaning products, as well as being by-products of some industrial processes. The aim of this study was to examine the effects of a sub-chronic exposure of NPs on various biological systems, using mice as a model. Adult male mice were administered 500 nm polystyrene (PS) NPs at 0.15 mg/day and 1.5 mg/day, to mimic subchronic exposure to NPs. Control mice were gavaged in the same manner but with sterile water instead of NPs. The mice were weighed weekly and treated daily for 60 days. The mice were then euthanized, and multiple tissues were retrieved and fixed or frozen for subsequent analyses. The intestines were rinsed and divided into pieces of the three regions: duodenum, jejunum, and ileum. Hematoxylin and eosin (H&E) staining was performed to evaluate histopathology, and RNA-Seq was conducted on tissues from all three regions. H&E staining revealed few effects on the duodenum, but increasingly pronounced disruption and epithelial alterations in the jejunum and ileum, respectively. RNA-Seq analysis of controls compared to the high-dose (HD; 1.5 mg/day) group supported these observations. The number of differentially expressed genes (DEGs) was low (19) in the duodenum, higher in the jejunum (114 DEGs), and significantly greater in the ileum (4982 DEGs). Genes associated with immune response, ion transport, and junctional proteins were among the groups of genes most differentially expressed. These results demonstrate the potentially harmful effects of PS NPs on the intestinal system of mice.

pharmacology and toxicology↗

bioRxiv2025

Accumulation of LRRK2-associated phospho-Rab12 degenerative lysosomes in tauopathies

Parkinsons disease (PD) pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with endolysosomal dysfunction across cell types, and carriers of LRRK2 mutations variably present with phosphorylated tau and -synuclein deposits in post-mortem analysis. LRRK2 mutations increase the phosphorylation of Rab substrates including Rab12. Rab12 is expressed in neuronal and non-neuronal cells with localization to membranes in the endolysosomal compartment. Under lysosomal stress, LRRK2 interaction with Rab12 upregulates LRRK2 kinase activity. In this study, using a recently developed monoclonal antibody directed to the LRRK2-mediated phosphorylation site on Rab12 at amino acid Ser106 (pS106-Rab12), we test whether aberrant LRRK2 phosphorylation is associated with tau and/or -synuclein pathology across clinically distinct neurodegenerative diseases. Analysis of brain tissue lysates and immunohistochemistry of pathology-susceptible brain regions demonstrate that pS106-Rab12 levels are increased in Dementia with Lewy bodies (DLB), Alzheimers disease (AD), and PD, and in LRRK2 mutation carriers. In early pathological stages, phosphorylated Rab12 localizes to granulovacuolar degeneration bodies (GVBs), which are thought to be active lysosomal-like structures, in neurons. pS106-Rab12-positive GVBs accumulate with pathological tau across brain tissues in DLB, AD, and PD, and in LRRK2 mutation carriers. In a mouse model of tauopathy, pS106-Rab12 localizes to GVBs during early tau deposition in an age-dependent manner. While GVBs are largely absent in neurons with mature protein pathology, subsets of both tau and -synuclein inclusions appear to incorporate pS106-Rab12 at later pathological stages. Finally, pS106-Rab12 labels GVBs in neurons and shows widespread co-pathology with tau inclusions in primary tauopathies including Picks disease, progressive supranuclear palsy and corticobasal degeneration. These results implicate LRRK2 kinase activity and Rab phosphorylation in endolysosomal dysfunction in both tau and -synuclein-associated neurodegenerative diseases.

neuroscience↗

bioRxiv2022

Intercellular CRISPR Screens Enhance the Discovery of Cancer Immunotherapy Targets

Cancer immunotherapy works through the interplay between immune and cancer cells. Particularly, interactions between cytotoxic T lymphocytes (CTLs) and cancer cells, such as PDCD1 (PD-1) and CD274 (PD-L1), are crucial for removing cancer cells. However, immune checkpoint inhibitors targeting these interactions are effective only to a subset of patients, requiring the development of novel immunotherapy drugs with novel targets. Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening in either cancer or immune cells has been used to discover regulators of immune cell function as immunotherapeutic targets. However, the method has two main limitations. First, performing CRISPR screens in one cell type alone makes it difficult to identify essential intercellular interactions due to the focus on single genes instead of interactions. Second, pooled screening is associated with high noise levels. Therefore, we propose intercellular CRISPR screens, which perform genome-wide CRISPR screening in every interacting cell type to discover intercellular interactions as immunotherapeutic targets. Intercellular CRISPR screens use two individual genome-wide CRISPR screens one each in immune and cancer cells to evaluate intercellular interactions that are crucial for killing cancer cells. We used two publicly available genome-wide CRISPR screening datasets obtained while triple-negative breast cancer (TNBC) cells and CTLs were interacting. We analyzed 4825 interactions between 1391 ligands and receptors on TNBC cells and CTLs to assess the effects of intercellular interactions on CTL function by incorporating both CRISPR datasets and the expression levels of ligands and receptors. Our results showed that intercellular CRISPR screens discovered targets of approved drugs, a few of which were not identifiable using single datasets. To quantitatively evaluate the methods performance, we used data for cytokines and costimulatory molecules because they constitute the majority of immunotherapeutic targets. Combining both CRISPR datasets improved the F1 score of discovering these genes relative to using single CRISPR datasets by more than twice. Our results indicate that intercellular CRISPR screens can identify novel immune-oncology targets that were not obtained using individual CRISPR screens. The pipeline can be extended to other cancer and immune cell types, such as natural killer cells, to identify important intercellular interactions as potential immunotherapeutic targets.

immunology↗