Biology subjects

Chen, S.-S.

Publications and source records attributed to Chen, S.-S..

6 recordsLinked to original sources

bioRxiv2025

IGLV3-21-R110-directed bispecific antibodies activate T cells and promote killing in a high-risk subset of chronic lymphocytic leukemia

We previously used a disease-specific B cell receptor (BCR) point mutation (IGLV3-21R110) for selective targeting of a poor-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. Since CLL is a disease of the elderly and a significant fraction of patients is not able to physically tolerate CAR T cell treatment, we explored bispecific antibodies as an alternative for precision targeting of this tumor mutation. Heterodimeric IgG1-based antibodies consisting of a fragment crystallizable region (Fc) attached to either an anti-IGLV3-21R110 Fab or an anti-CD3 (UCHT1) single chain variable fragment (R110-bsAb) selectively killed cell lines engineered to express high levels of the neoepitope as well as primary CLL cells using healthy donor and CLL patient-derived T cells as effectors. R110-bsAb spared polyclonal human B cells (as opposed to CD19-targeting Blinatumomab) as well as CD34+ human stem cells. Yet, R110-bsAb induced lower T cell activation than Blinatumomab with primary CLL cells likely due to lower expression of target antigen. In vivo, R110-bsAb specifically killed IGLV3-21R110-expressing cell lines and CLL cells while sparing peripheral blood mononuclear cells. These findings highlight bispecific antibodies as a promising, off-the-shelf immunotherapy for high-risk CLL patients, offering selective targeting while preserving healthy B cells.

cancer biology↗

bioRxiv2024

Chromosomal-level reference genome and microRNAs of the ricefield flatsedge Cyperus iria

BackgroundGrass-like plants in the Cyperaceae family, commonly known as sedges, have a global distribution and include many economically problematic weeds. The ricefield flatsedge, Cyperus iria, is an aggressive weed in rice crops in Asia. ResultHere, we present a chromosomal-level genome assembly for C. iria (461.2 Mb, scaffold N50 = 7.3 Mbp, 99.6% BUSCO score) providing potential targets for the control of this devastating weed. Based on the genome assembly and transcriptomes of vegetative tissues, 52,574 protein-coding genes were predicted to be encoded. A total of 26 conserved and 75 novel microRNAs, including 9 microRNA clusters, were also annotated. Synteny and microRNA cluster analyses further showed that C. iria had undergone at least one round of whole genome duplication. ConclusionThe genomic resource established in this study sets up a foundation to further address basic and applied questions in the Cyperaceae.

genomics↗

bioRxiv2024

The Taiwan Precision Medicine Initiative: A Cohort for Large-Scale Studies

The Taiwan Precision Medicine Initiative (TPMI), a project initiated by the Academia Sinica in collaboration with 16 major medical centers around Taiwan, has recruited 565,390 participants who consented to provide DNA samples for genetic profiling and grant access to their electronic medical records (EMR) for studies to develop precision medicine. Access to the EMR is both retrospective and prospective, allowing researchers to conduct prospective studies over time. Genetic profiling is done with population-optimized SNP arrays for the Han Chinese populations that enable genetic analyses such as genome-wide association, phenome-wide association, and polygenic risk score studies to evaluate common disease risk and pharmacogenetic response. Furthermore, the TPMI participants agree to be contacted for future research opportunities related to their genetic risks and receive personalized genetic risk profiles with health management recommendations. TPMI has established the TPMI Data Access Platform (TDAP), a central database and analysis platform that both safeguards the security of the data and facilitates academic research. The TPMI is the largest non-European cohort that merges genetic profiles with EMR in the world. With a cohort that can be followed over time, it can be utilized to validate genetic risk prediction models, conduct clinical trials to show the efficacy of risk-based health management, and optimize health policies based on genetic risks. In this report, we describe the TPMI study design, the population and genetic characteristics of the TPMI cohort, and the power it provides to conduct crucial studies in developing precision medicine on a population and personal level. As Han Chinese represent almost 20% of the worlds population, the results of TPMI studies will benefit >1.4 billion people around the world and serve as a model for developing population-based precision medicine.

genetics↗

bioRxiv2024

Guard-cell phytosterol homeostasis is critical for proper stomatal development

Stomata regulate gas exchange and control water loss in response to the environmental stimuli and their distribution in the leaf epidermis is tightly regulated during development to ensure proper patterns. Although many studies have focused on the function of early stomatal lineage cells, little is known about the role of mature guard cells (GCs) in maintaining stomatal distribution. Here, we identified a previously uncharacterized enzyme, GDSL-type sterol esterase (GSEase), that is specifically expressed in mature guard cells and catalyzes lipid droplet-stored phytosterol ester degradation. Loss of GSEase decreased the level of free campesterol, a biosynthetic precursor of brassinosteroids (BRs), reduced BR level, and increased stomatal density in leaves, which could be further rescued by increasing the BR signaling. Furthermore, selectively reducing the BR response in GCs by utilizing the GSEase promoter-driven det2-1, a mutation causing BR biosynthesis deficiency, resulted in an elevated stomatal count, as demonstrated in gsease plants. These results indicate that GSEase plays a critical role in maintaining phytosterol homeostasis in GCs and the released phytosterols suppress the initiation of stomatal development in adjacent cells though the BR pathway.

plant biology↗

bioRxiv2023

Title: Abrogation and Homeostatic Restoration of IgE Responses by a Universal IgE Allergy CTL Vaccine:The Three Signal Self/Non-Self/Self (S/NS/S) Model

Natural IgE cytotoxic peptides (nECPs), which are derived from the constant domain of the heavy chain of human IgE producing B cells via endoplasmic reticulum (ER) stress, are decorated onto MHC class 1a molecules (MHCIa) as unique biomarkers for CTL (cytotoxic T lymphocyte)-mediated immune surveillance. Human IgE exhibits only one isotype and lacks polymorphisms; IgE is pivotal in mediating diverse, allergen-specific allergies. Therefore, by disrupting self-IgE tolerance via costimulation, the cytotoxic T lymphocytes (CTLs) induced by nECPs can serve as universal allergy vaccines (UAVs) in humans to dampen IgE production mediated by diverse allergen-specific IgE- secreting B cells and plasma cells expressing surface nECP-MHCIa as targets. The study herein has enabled the identification of nECPs produced through the correspondence principle 1, 2. Furthermore, nECP-tetramer-specific CTLs were found to be converted into CD4 Tregs that restored IgE competence via the homeostatic principle, mediated by SREBP-1c suppressed DCs. Thus, nECPs showed causal efficacy and safety as UAVs for treating type I hypersensitivity IgE-mediated allergies. The applied vaccination concept presented provides the foundation to unify, integrate through a singular class of tetramer-specific TCR clonotypes. The three signal model is proposed on the mechanisms underlying central tolerance, breaking tolerance and regaining peripheral tolerance via homeostasis concerning nECP as an efficacious and safe UAV to treat type I IgE-mediated hypersensitivity. One Sentence SummaryHuman IgE self-peptides are identified as universal allergy vaccines that inhibit IgE synthesis while allowing homeostatic IgE recovery. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/561777v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@18cb814org.highwire.dtl.DTLVardef@1893312org.highwire.dtl.DTLVardef@78221aorg.highwire.dtl.DTLVardef@1071098_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphic abstract text Three cell S/NS/S model of Universal Allergy Vaccines (UAV): Natural IgE peptides (nECPs) presented by enabler DCs break central IgE tolerance (Self), leading to CTLs that inhibit IgE production (Non-self). Generative DCs converted by the metabolic milieu transform the pre-existing nECP-specific CTLs into nECP-specific Tregs leading to homeostatic recovery of IgE competence (S).

immunology↗

bioRxiv2023

Mutation-specific CAR T cells as precision therapy for IGLV3-21R110 expressing high-risk chronic lymphocytic leukemia

The concept of precision cell therapy targeting tumor-specific mutations is appealing but requires surface-exposed neoepitopes, which is a rarity in cancer. B cell receptors (BCR) of mature lymphoid malignancies are exceptional in that they harbor tumor-specific-stereotyped sequences in the form of point mutations that drive self-engagement of the BCR and autologous signaling. Here, we used a BCR light chain neoepitope defined by a characteristic point mutation (IGLV3-21R110) for selective targeting of a poor-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. We developed murine and humanized CAR constructs expressed in T cells from healthy donors and CLL patients that eradicated IGLV3-21R110 expressing cell lines and primary CLL cells, but not polyclonal healthy B cells. In vivo experiments confirmed epitope-selective cytolysis in xenograft models using engrafted IGLV3-21R110 expressing cell lines or primary CLL cells. We further demonstrate in two humanized mouse models lack of cytotoxicity towards human B cells. These data provide the basis for novel avenues of resistance-preventive and biomarker-guided cellular targeting of functionally relevant lymphoma driver mutations sparing normal B cells.

cancer biology↗