Biology subjects

Ferris, D.

Publications and source records attributed to Ferris, D..

5 recordsLinked to original sources

bioRxiv2025

Precision targeting of autoreactive B cells in systemic lupus erythematosus using anti-9G4 idiotope synthetic immune receptor T cells

Chimeric antigen receptor (CAR)-T cell therapies can induce drug-free remission in systemic lupus erythematosus (SLE), but indiscriminate B cell targeting causes immunosuppression, unnecessary infections, and cytokine toxicities that preclude widespread use. Here, we overcome this by targeting the 9G4 idiotope, a shared structural feature of pathogenic B cell receptors encoded by the IGHV4-34 gene. We engineered anti-9G4 CAR-T cells and chimeric TCR-T cells to selectively eliminate autoreactive B cells while preserving protective immunity. Both platforms eradicated autoreactive B cells and autoantibodies in vitro and in vivo, spared normal B cells, and markedly reduced cytokine release compared to conventional CAR-T cells. This precision extended to cold agglutinin disease and lymphoma. These findings establish a framework for IGHV idiotope-directed cellular therapies for treating autoimmune and neoplastic diseases while preserving immune competence.

immunology↗

bioRxiv2025

Anti-citrullinated protein antibodies arise during affinity maturation of germline antibodies to carbamylated proteins in rheumatoid arthritis

Why autoantibodies in rheumatoid arthritis (RA) primarily target physiologically modified proteins, called citrullinated proteins, is unknown. Recognizing the inciting event in the production of anti-citrullinated protein antibodies (ACPAs) may shed light on the origin of RA. Here, we demonstrate that ACPAs originate from germline-encoded antibodies targeting a distinct but structurally similar modification, called carbamylation, which is pathogenic and environmentally driven. The transition from anti-carbamylated protein (anti-CarP) antibodies to ACPAs results from somatic hypermutations, indicating that the change in reactivity is acquired via antigen-driven affinity maturation. During this process, a single germline anti-CarP antibody transitions from anti-CarP to double positive (anti-CarP/ACPA) to ACPA according to the pattern and number of somatic hypermutations, explaining their coexistence and diverse specificity in RA. Artificial intelligence-based structural modeling revealed that an ACPA and its germline precursor exhibit distinct structural and biophysical properties, and pointed to heavy-chain tryptophan 48 (H-W48) as a critical residue in the differential recognition of citrullinated vs. carbamylated proteins. Indeed, a single methionine substitution in H-W48 changes the antibody specificity from ACPA to anti-CarP. These data indicate that the existence of germline-encoded anti-CarP antibodies is most likely the first event in the production of ACPAs during the early stages of RA development.

immunology↗

bioRxiv2022

Practice walking on a treadmill-mounted balance beam modifies beam walking sacral movement and alters performance in other balance tasks

The goals of this study were to determine if a single 30-minute session of practice walking on a treadmill-mounted balance beam: 1) altered sacral marker movement kinematics during beam walking, and 2) affected measures of balance during treadmill walking and standing balance. Two groups of young, healthy human subjects practiced walking on a treadmill-mounted balance beam for thirty minutes. One group trained with intermittent visual occlusions and the other group trained with unperturbed vision, providing greater variation in the balance performance outcomes. We hypothesized that the subjects would show changes in sacrum movement kinematics after training and that there would be group differences due to larger improvements in beam walking performance by the visual occlusions group. We also investigated if there was any balance transfer from training on the beam to treadmill walking (margin of stability) and to standing static balance (center of pressure excursion). We found significant differences in sacral marker maximal velocity after training for both groups, but no significant differences between the two groups from training. There was limited evidence of balance transfer from beam walking practice to gait margin of stability for treadmill walking and for single-leg stance balance, but not for tandem stance balance. The number of step-offs while walking on a narrow beam had the largest change with training (partial {eta}2=0.7), in accord with task specificity. Other balance metrics indicative of transfer had lower effect sizes (partial {eta}2<0.5). Given the limited transfer across balance training tasks, future work should examine how intermittent visual occlusions during multi-task training improve real world functional outcomes.

physiology↗

bioRxiv2022

Visual Occlusions Result in Phase Synchrony Within Multiple Brain Regions Involved in Sensory Processing and Balance Control

There is a need to develop appropriate balance training interventions to minimize the risk of falls. Recently, we found that intermittent visual occlusions can substantially improve the effectiveness and retention of balance beam walking practice (Symeonidou and Ferris 2022). We sought to determine how the intermittent visual occlusions affect electrocortical activity during beam walking. We hypothesized that areas involved in sensorimotor processing and balance control would demonstrate spectral power changes and inter-trial coherence modulations after loss and restoration of vision. Ten healthy young adults practiced walking on a treadmill-mounted balance beam while wearing high-density EEG and experiencing reoccurring visual occlusions. Results revealed spectral power fluctuations and inter-trial coherence changes in the visual, occipital, temporal, and sensorimotor cortex as well as the posterior parietal cortex and the anterior cingulate. We observed a prolonged alpha increase in the occipital, temporal, sensorimotor, and posterior parietal cortex after the occlusion onset. In contrast, the anterior cingulate showed a strong alpha and theta increase after the occlusion offset. We observed transient phase synchrony in the alpha, theta, and beta bands within the sensory, posterior parietal, and anterior cingulate cortices immediately after occlusion onset and offset. Our results provide support for cross-modal phase resetting and enhanced processing in areas involved in sensory processing and balance control as an explanation for increased long-term balance improvement when training with intermittent visual occlusions. Our training intervention could be implemented in senior and rehabilitation centers, improving the quality of life of elderly and neurologically impaired individuals.

neuroscience↗

bioRxiv2020

A model-based analysis of the mechanical cost of walking on uneven terrain

Human walking on uneven terrain is energetically more expensive than on flat, even ground. This is in part due to increases in, and redistribution of positive work among lower limb joints. To improve understanding of the mechanical adaptations, we performed analytical and computational analyses of simple mechanical models walking over uneven terrain comprised of alternating up and down steps of equal height. We simulated dynamic walking models using trailing leg push-off and/or hip torque to power gait, and quantified the compensatory work costs vs. terrain height. We also examined the effect of swing leg dynamics by including and excluding them from the model. We found that greater work, increasing approximately quadratically with uneven terrain height variations, was necessary to maintain a prescribed average forward speed. Greatest economy was achieved by modulating precisely-timed push-offs for each step height. Least economy was achieved with hip power, which did not require as precise timing. This compares well with observations of humans on uneven terrain, showing similar near-normal push-off but with more variable step timing, and considerably more hip work. These analyses suggest how mechanical work and timing could be adjusted to compensate for real world environments.

bioengineering↗