Biology subjects

Broderick, T.

Publications and source records attributed to Broderick, T..

4 recordsLinked to original sources

bioRxiv2026

Translating Innovation to Clinic: End-to-End Bioprocess Development and cGMP Manufacturing of N332-GT5 HIV Vaccine Candidate for First-in-Human Trials HVTN144

The successful translation of rationally designed HIV-1 immunogens into effective vaccines requires manufacturing platforms that maintain structural conformity while meeting clinical-grade quality standards. We developed and scaled a robust, cGMP-compliant process for N332-GT5 gp140, a germline-targeting envelope trimer designed to initiate broadly neutralizing antibody responses, which is now undergoing first-in-human evaluation in HVTN144. Starting with a stable CHO cell line developed using Leap-In(R) transposon technology, we established a production clone exhibiting high-titer expression (>200 mg/L) and genetic stability through 60 population doublings. The manufacturing process scaled efficiently from Ambr(R) 250 miniature bioreactors to 200-L single-use systems, delivering consistent product quality across multiple cGMP batches. A streamlined three-step purification strategy--affinity capture, multimodal polishing, and viral clearance- yielded >99% trimeric purity with preserved quaternary structure and native-like antigenicity. Orthogonal LC-MS analyses confirmed site-specific glycan occupancy matching design specifications, while robust viral clearance exceeded 18-log and 11-log reductions for model retroviruses. Clinical material manufactured through this platform has been successfully administered in HVTN144. This work establishes a scalable, reproducible manufacturing paradigm for structurally complex HIV-1 envelope immunogens, advancing the field toward rational vaccine design based on germline-targeting principles.

bioengineering↗

bioRxiv2025

DNA Methylation Dynamics of Dose-dependent Acute Exercise, Training Adaptation, and Detraining

Exercise and diet are direct physical contributors to human health, wellness, resilience, and performance1-5. Endurance and resistance training are known to improve healthspan through various biological processes such as mitochondrial function6-8, telomere maintenance9, and inflammaging10. Although several training prescriptions have been defined with specific merits 1,10-20, the long-term effects of these in terms of their molecular alterations have not yet been well explored. In this study, we focus on two combined endurance and resistance training programs: (1) traditional moderate-intensity continuous endurance and resistance exercise (TRAD) and (2) a variation of high-intensity interval training (HIIT) we refer to as high intensity tactical training (HITT), to assess the dynamics of DNA methylation (DNAm) in blood and muscle derived from males (N=23) and females (N=31), over a 12-week period of training followed by a 4-week period of detraining, sampled at pre-exercise and acute time points, totaling 528 samples. Due to its rapid responsiveness to stimuli and its stability, DNAm has been known to facilitate regulatory cascades that significantly affect various physiological processes and pathways. We find that several thousand differentially methylated regions (DMRs) associated with acute exercise in blood, many of which are shared across males and females. This trend is reversed when comparing the baseline (pre-exercise) time points or post-exercise timepoints at the untrained state with those at the post-conditioned state. Here, muscle shows majority of DNAm changes, with most of those being unique. We also find several hundred "memory" DMRs in muscle that maintain the gain or loss of methylation after four weeks of inactivity. Comparing phenotypic measurements, we find specific DMRs that correlate significantly with mitochondrial function and myofiber switching. Using machine learning, we select a subset of DMRs that are most characteristic of training modalities, sex and timepoint. Most of the DMRs are enriched in pathways associated with immune function, cell differentiation, and exercise adaptation. These findings reveal mechanisms by which exercise- and training-induced epigenetic changes alter immune surveillance, mitochondrial function, and inflammatory response, and underscore the relevance of epigenetic plasticity to health monitoring and wellness.

genomics↗

bioRxiv2024

RID-Rihaczek Phase Synchrony Method Applied to Resting-State EEG: Simultaneous prediction of visuospatial tracking, verbal communication, executive function, neuro-cognitive health, and intelligence

Brain activity at a resting state and functional connectivity represent individuals neural configurations that can be used to predict various performance and trait measures. Yet, most of the previous empirical demonstrations of this phenomena are limited to using resting-state neuroimaging to predict a single task performance/trait measure, and a few studies that predicted multiple task performance/traits measures employed conceptually similar tasks to produce converging evidence for their topic of investigation. In the current paper, we applied RID-Rihazcek phase synchrony, a nonlinear time-frequency-based method for neural computation, to resting-state EEG data and simultaneously predicted a wide variety of measures: standard shooting task performance and novel verbal communication-based team shooting task performance in a simulator, visuo-spatial tracking task performance (Neurotracker), executive function (verbal fluency task), fluid and crystalized Intelligence (Multidimensional Aptitude Battery II: MAB-II), and neurocognitive functioning (Automated Neuropsychological Assessment Metrics-4: ANAM-4) with the average R2 = .60. Our findings show great promise for RID-Rihazcek phase synchrony and resting-state EEG in general to be used in aptitude assessment.

neuroscience↗

bioRxiv2024

Serum metabolomics signatures after an acute bout of combined traditional or high-intensity tactical training in young males and females

Exercise is a multipotent stimulus that results in large-scale dynamic changes to the systemic molecular profile. Alternative exercise prescriptions and doses would be expected to result in distinct signatures due to differences in duration and intensity. We tested two novel combined endurance and resistance exercise regimens to better understand how differing prescriptions alter the acute metabolomics response at multiple timepoints up to 24h post-exercise. Serum metabolomics for n=37 untrained individuals was analyzed for participants completing traditional combined exercise [TRAD; n = 20 (11M/9F)] or high-intensity tactical training [HITT; n= 17 (8M/9F)] before exercise (pre), and immediately (h0), 3 and 24 h post-exercise (h3 and h24, respectively). We found minimal metabolites had a group by time interaction (2 with FDR < 0.10; 31 with nominal p < 0.05;), but both stimuli resulted in large-scale within-group changes to the circulating metabolome. TRAD consistently had greater numbers of differentially abundant metabolites (FDR < 0.10) as compared to HITT at h0 (431 vs. 333), h3 (435 vs. 331) and h24 (168 vs. 76). The major metabolite classes altered were related to key energy substrates for both groups at h0 (e.g., glucose, pyruvate) and energy replenishment for h3 and h24 (e.g., 12,13 diHOME, palmitoylcarnitine, free fatty acids). In summary, our data are the first to describe the acute changes in the circulating metabolome following combined endurance and resistance exercise. Additionally, we show the two distinct doses of combined exercise led to generally similar patterns of responses, with the longer duration TRAD dose resulting in a higher magnitude of change.

physiology↗