Biology subjects

Liberman, A.

Publications and source records attributed to Liberman, A..

2 recordsLinked to original sources

bioRxiv2026

Dual Immune Checkpoint and Cytokine Receptor Modulation by an Engineered Human CTLA-4/IL-10 Bispecific Fusion Protein

Bispecific fusion proteins represent a unique strategy for developing precision therapeutics. By linking functional domains from distinct proteins, these biomolecules can engage multiple targets, enhancing both therapeutic efficacy and safety. Unlike bispecific antibodies, low-molecular-weight fusion proteins offer distinct advantages, including reduced immunogenicity and superior tissue penetration due to their relatively compact size and structure. Such a profile is particularly valuable in managing complex inflammatory diseases, where modulating multiple pathways is required to impart an effective anti-inflammatory effect. Among the various regulators of immune signaling, the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and interleukin-10 (IL-10) play imperative roles in immune suppression through their interactions with CD80/86 and IL-10R, respectively. While Fc-fused CTLA-4 is a clinically approved drug (e.g., Abatacept), the clinical development of IL-10 has been hampered by unpredictable immunostimulatory side effects. Here, we engineered a bispecific fusion protein linking the extracellular domain of CTLA-4 to IL-10. We successfully expressed the protein in E. coli as an N-terminal GST-tagged variant and refolded it from the inclusion bodies. Additionally, we achieved soluble expression of an Fc-tagged variant in mammalian CHO cells. Both origins demonstrated binding to their cognate receptors, CD80 and IL-10R. Finally, the fusion protein demonstrated a T cell-inhibitory effect by reducing Interferon-{gamma} (IFN{gamma}) secretion levels in an in vitro human Virus-Specific T cells (VSTs) model. This innovative protein engineering offers a promising strategy for addressing unmet clinical needs in autoimmune and inflammatory diseases.

bioengineering↗

bioRxiv2018

Serial Dependence in Position Perception Occurs at the Time of Perception

Observers perceive objects in the world as stable over space and time, even though the visual experience of those objects is often discontinuous and distorted due to masking, occlusion, camouflage, noise, etc. How are we able to easily and quickly achieve stable perception in spite of this constantly changing visual input? It was previously shown that observers experience serial dependence in the perception of features and objects, an effect that extends up to 15 seconds back in time. Here, we asked whether the visual system utilizes an objects prior physical location to inform future position assignments in order to maximize location stability of an object over time. To test this, we presented subjects with small targets at random angular locations relative to central fixation in the peripheral visual field. Subjects reported the perceived location of the target on each trial by adjusting a cursors position to match its location. Subjects made consistent errors when reporting the perceived position of the target on the current trial, mislocalizing it toward the position of the target in the preceding two trials (Experiment 1). This pull in position perception occurred even when a response was not required on the previous trial (Experiment 2). In addition, we show that serial dependence in perceived position occurs immediately after stimulus presentation, and is a fast stabilization mechanism that does not require a delay (Experiment 3). This indicates that serial dependence occurs for position representations and facilitates the stable perception of objects in space. Taken together with previous work, our results show that serial dependence occurs at many stages of visual processing, from initial position assignment to object categorization.

neuroscience↗