Topic: Identification of HLA-A, HLA-B, and HLA-C Triple Homozygous and Double Homozygous Donors in the Lithuanian Population: A Path toward Synthetic Superdonor Advanced Therapeutic Medicinal Products

Human-induced pluripotent stem cells with broad immune compatibility are highly desirable for regenerative medicine applications. Human leukocyte antigen (HLA) class I homozygous cell sources are ideal for immune compatibility modeling.

Here, we profile HLA-A, HLA-B, and HLA-C alleles in 3,496 Lithuanian donors genotyped at three-field resolution. The five most frequent alleles constitute 74.6% of HLA-A, 43.2% of HLA-B, and 59.2% of HLA- C, with HLA-A*02:01:01, HLA-B*07:02:01, and HLA-C*07:02:01 being the most common. Lithuanian allele frequencies closely resemble those of European- American and British populations.

We identified 153 double homozygotes and 51 triple homozygotes for HLA-A, HLA-B, and HLA-C. Compatibility modeling showed that triple homozygous profiles match 60.5% of Lithuanians, 13.4% of the British population, and 7.4% of European-Americans. CRISPR-Cas9 guide RNA design yielded 54 candidates predicted to disrupt HLA-A or HLA-B while preserving HLA-C, producing edited profiles matching over 97.9% of Lithuanians, 95.7% of European-Americans, and 95.5% of the British population.

Finally, we established 15 fibroblast lines from triple homozygotes as a bioresource for the derivation of human-induced pluripotent stem cells and immune compatibility studies.

Topic: Place-of-Care CAR-T Cell Program for Treatment of CD19-Positive Malignancies at Vilnius University Hospital Santaros Klinikos

Abstract to be announced shortly.

Topic: Cryogenic and Room-temperature X-ray Studies of Urocanate Reductase 

Urocanate reductase is a bacterial enzyme present in certain members of the human gut microbiota. It catalyzes the production of imidazole propionate, a metabolite that has been linked to type 2 diabetes and other diseases.

We applied X-ray crystallography to gain insight into the enzymatic mechanism and active-site dynamics. By combining cryogenic and room-temperature data collection, we reveal distinct conformational states of the enzyme, highlight the dynamics of key catalytic residues, and uncover the influence of small modulating molecules in the active site.

Beyond the biological findings, this study also illustrates the advantages and limitations of crystallographic data collection at different temperatures.

Topic: Extracellular Vesicles: A Long and Winding Journey toward Clinical Translation

Extracellular vesicles (EVs) are heterogeneous, lipid bilayer-enclosed vesicles that can act as transport vehicles for various biologically active molecules. Initially considered as an additional mechanism for the removal of cellular waste, EVs are now being increasingly recognized as a new mode for intercellular communication.

Although numerous pre-clinical studies over the past decade have demonstrated therapeutic potential of EVs, broad clinical application remains a distant goal. This is primarily due to two major challenges. First, large-scale manufacturing is required to produce the substantial quantities of EVs necessary for clinical applications, which may impact their composition and therapeutic properties. Second, developers of EV therapeutic products are expected to provide detailed information about their mode of action (MoA). Given the immense molecular complexity of EVs, determining their specific MoA often poses a significant challenge.

In the first part of my talk, I will introduce the audience to the exciting world of EVs. Next, I will present our recent advancements in developing new technology for large-scale EV production, suitable for preclinical and early-phase clinical trials targeting Parkinson’s disease. Finally, I will discuss our findings in the context of the challenges outlined earlier.

Topic: Next-generation Ion Source for Low-flow LC–MS: Maximum Performance Across Systems and Users

To help customers advance scientific discovery, Thermo Fisher Scientific unveiled the Thermo Scientific™ OptiSpray™ technology at the ASMS 2025 conference in Baltimore. High-quality data is essential for modern mass spectrometry applications such as proteomics, single-cell analysis, metabolomics, and biomarker discovery – especially as researchers increasingly work with smaller sample amounts and demand high sensitivity and precision.

Achieving optimal performance in low-flow LC-MS can be challenging due to emitter positioning and electrospray stability issues. The Thermo Scientific™ OptiSpray™ ion source addresses these challenges by integrating separation column, liquid junction, and replaceable emitter into a single cartridge unit. Combined with a motorized XYZ stage and software-driven optimization routines, OptiSpray automates emitter alignment based on real signal, minimizing user variability and improving reproducibility.

This design streamlines setup, improves stability, and enhances overall robustness. Whether applied to high-throughput or low-input analyses, OptiSpray enables reliable and sensitive detection of low-abundance features without compromising chromatographic performance, while greatly improving precision.

Compatible with Thermo Fisher Scientific mass spectrometers – Orbitrap™ Astral™, Orbitrap Tribrid™, Orbitrap Excedion™ Pro, Stellar™, and TSQ Plus™ systems – OptiSpray brings confidence and ease to workflows, empowering researchers of all experience levels to generate high-quality LC-MS data across platforms and expedite critical discoveries.

Topic: Psoriatic Inflammation Revisited: Mitochondrial Dynamics and Therapeutic Cues from the Plant Secretome

Psoriasis is a chronic skin disease affecting 2-3% of the global population. Systemic biologics offer advanced treatment but have variable responses and side effects. Understanding disease mechanisms is key for better therapies.

Recent studies highlight mitochondrial dynamics in psoriasis progression, but real-time monitoring tools were lacking. We used Stimulated Emission Depletion (STED) microscopy to visualize mitochondrial changes in live cells under psoriasis-like inflammation, showing network reorganization down to cristae structures. Intercellular communication via the secretome is crucial in inflammation, with vesicle-mediated signaling effective across species.

We explored plant-derived nanovesicles (PDNVs) from Melissa officinalis, which restored mitochondrial networks and reduced inflammation in psoriasis-like cells.

3D human skin models, mimicking native skin architecture, provide a platform for therapeutic evaluation, potentially reshaping the study and treatment of inflammatory skin diseases.