Biology subjects

Lee, D. K.

Publications and source records attributed to Lee, D. K..

6 recordsLinked to original sources

bioRxiv2025

Precision at Every Scale: Efficiency in AI-Driven De Novo Antibody Design

The precise de novo design of antibodies remains a therapeutic challenge. The AI platform, GaluxDesign, was evaluated in a high-efficiency Precision-Scale Workflow by synthesizing and testing only 50 full-length IgG candidates per epitope across eight distinct epitopes from six therapeutic targets. This campaign yielded a 10.5% binder rate (estimated EC50 < 100 nM), identifying target-specific binders for seven of eight epitopes, with multiple candidates exhibiting sub-nanomolar to single-digit nanomolar dissociation constants (Kd). We further assessed the same workflow on nine shared benchmark targets selected for external comparison, where GaluxDesign identified target-specific binders for eight of nine targets, demonstrating strong target-level performance relative to previously reported de novo antibody design approaches. Together, these results establish a high-efficiency, precision-scale workflow for generating novel, high-affinity therapeutic antibodies.

bioengineering↗

bioRxiv2025

Isolation free Identification and Phenotyping of First Trimester Extravillous Trophoblasts Residing in Cervical Fluid

Preeclampsia (PE) remains difficult to predict, particularly when it manifests late in gestation. To capture early placental signals, we profiled trophoblast cells sampled from the cervix in the first trimester using mass cytometry (CyTOF). We established protocols for clinical sample storage and applied spike-in reference control cells to deliver reproducible, batch-corrected protein measurements, thereby advancing CyTOF from a discovery tool to a translational platform. Within HLA-GCD45- cells, we identified canonical CK7 extravillous trophoblasts, as well as a previously unrecognized CK7-subset, and both subsets expressed placental proteins. Expression of PAPP-A, GAL-13, and GAL-14 was significantly altered in a pilot cohort of pregnancies that subsequently developed late-onset PE, distinguishing cases from controls at both single-marker and multivariate levels. These findings reveal unexpected trophoblast heterogeneity, demonstrate that placental alterations are detectable before the development of late-onset PE, and establish cervical trophoblast profiling as a promising platform for scalable biomarker discovery and first-trimester risk assessment in placenta-mediated disorders. Impact StatementFirst-trimester trophoblasts sampled from the cervix reveal early molecular changes associated with late-onset preeclampsia, while an isolation-free, reference-normalized CyTOF workflow establishes a scalable, clinically compatible platform for biomarker discovery and multicenter-ready early risk assessment in pregnancy.

cell biology↗

bioRxiv2024

Adherent-to-suspension transition promotes melanoma metastatic dissemination

Melanoma is a highly metastatic skin cancer that often evades current therapeutic strategies primarily because of the complex mechanisms involved in metastasis. This study investigated the role of adherent-to-suspension transition (AST) in melanoma and its potential to facilitate metastasis by reprogramming cellular anchorage dependency. Using melanoma models, we demonstrated that the AST factors IKZF1, IRF8, and NFE2 are crucial for reprogramming, influencing gene expression related to cell adhesion and survival. Notably, our results highlight that AST factor expression undergoes dynamic changes during metastasis, which can be reversed in circulating tumor cells. Our findings revealed that AST contributes to the increased metastatic potential and invasiveness of melanoma cells and underscores its role independent of the epithelial-to-mesenchymal-like transition pathways. Based on the results, we highlight the potential of targeting AST mechanisms to develop new therapeutic strategies against metastasis.

cancer biology↗

bioRxiv2024

Adherent-suspension plasticity promotes the dissemination and colonization of circulating tumor cells

Cell competition within the primary tumor drives tumor growth by promoting the uncontrolled proliferation of winner cells and eliminating loser cells by sensing cell fitness. However, the mechanism of how cell competition confers the loser cells with the metastatic potential of circulating tumor cells (CTCs) to transit between dissemination and colonization remains elusive. Here we found cell competition gives rise to less fit but viable cells that transformed into CTCs via adherent-to-suspension transition (AST) mechanisms. The induction of hematopoietic transcription factors hijacked by solid tumor cells rendered CTCs competent to reprogram their anchorage dependency and disseminate into the bloodstream, while subsequent suppression of these factors was critical to regain adhesion and colonize metastatic lesions. Disrupting the oscillatory dynamics of AST factors blocked the adherent-suspension plasticity (ASP) of breast cancer CTCs and suppressed lung metastasis. Furthermore, multiregional single-cell transcriptomic analyses of matched primary tumors, CTCs, and metastatic lesions from de novo metastatic breast cancer patients demonstrate the critical role of ASP in metastasis. SignificanceWe demonstrate cell competition-mediated displacement of loser cells manifests dynamic oscillation of AST factors that confer anchorage plasticity to circulating tumor cells critical for their dissemination and colonization in metastasis. These findings highlight the potential of targeting AST factors to develop effective anti-metastatic therapies.

cancer biology↗

bioRxiv2024

Phosphoinositide-focused CRISPR screen identifies novel genetic vulnerabilities in PDAC and AML cells

Phosphoinositides (PIs) are minor but essential phospholipids that play crucial roles in cellular signaling pathways, membrane dynamics, and the regulation of various cellular processes. We developed and utilized a novel PI-focused CRISPR gRNA library to perform negative-selection and positive-selection screens in PANC-1 and OCI-AML2 cells, models of pancreatic ductal adenocarcinoma (PDAC) and acute myeloid leukemia (AML), respectively. Through these screens, we identified 28 essential genes in PANC-1, 84 essential genes in OCI-AML2, and 28 regulators of colony formation in OCI-AML2. Our results using this small and focused library uncovered false negatives and subtle effects that may be missed in genome-wide approaches, while enabling adaptation to different screening conditions. Overall, our results uncovered previously uncharacterized essential genes in PDAC and AML that can be leveraged as therapeutic targets and biomarkers. We also demonstrate that focused libraries offer a more efficient and targeted approach to uncovering critical genetic determinants of cancer progression.

cancer biology↗

bioRxiv2020

Photoperiod Sensitive Energy Sorghum Responses to Environmental and Nitrogen Variabilities

Recently introduced photoperiod-sensitive (PS) biomass sorghum (Sorghum bicolor L. Moench) needs to be investigated for their yield potentials under different cultivation environments with reasonable nitrogen (N) inputs. The objectives of this study were to 1) evaluate the biomass yield and feedstock quality of four sorghum hybrids with different levels of PS ranging from very PS (VPS) hybrids and to moderate PS (MPS) hybrids, and 2) determine the optimal N inputs (0~168 kg N ha-1) under four environments: combinations of both temperate (Urbana, IL) and subtropical (College Station, TX) regions during 2018 and 2019. Compared to TX, the PS sorghums in central IL showed higher yield potential and steady feedstock production with an extended daylength and with less precipitation variability, especially for the VPS hybrids. The mean dry matter (DM) yields of VPS hybrids were 20.5 Mg DM ha-1 and 17.7 Mg DM ha-1 in IL and TX, respectively. The highest N use efficiency occurred at a low N rate of 56 kg N ha-1 by improving approximately 33 kg DM ha-1 per 1.0 kg N ha-1 input. Approximately 70% of the PS sorghum biomass can be utilized for biofuel production, consisting of 58-65% of the cell wall components and 4-11% of the soluble sugar. This study demonstrated that the rainfed temperate area (e.g., IL) has a great potential for the sustainable cultivation of PS energy sorghum due their observed high yield potential, stable production, and low N requirements.

plant biology↗