Joshua Justice | Proteogenomics Scientist
Johnson & Johnson
I am a proteomics scientist at Johnson & Johnson in the Cell Engineering and Analytical Sciences group. My mission at J&J is to leverage proteomics to drive innovations that will lead to the next generation of CHO hosts for bioproduction through cell engineering. My graduate work was at the University of Alabama at Birmingham where I studied oncogenic virus infection and interplay with the host cell cycle and DNA damage responses. My postdoctoral training at Princeton University focused on coupling cutting-edge proteomic analysis of protein interactions, post-translational modifications, and spatial regulation to uncover insights into viral immunity.
Appearances:
Festival of Biologics Day 2 @ 16:30
Multi-proteomic profiling of a CHO model system of lactate overproduction reveals insight into metabolic dysfunction during bioproduction
The bioproduction process places enormous metabolic strain on host cells. Cellular proliferation and the high translation rate of the therapeutic leads to rapid consumption of glucose, oxygen, and amino acids while producing metabolic by-products such as lactate. Typically, lactate is further consumed to meet the metabolic demand; however, occasionally lactate accumulation outpaces consumption leading to toxicity that impacts cellular growth and biomolecule production. In these cases, where lactate levels are unmanageable, product quality and titer may suffer. Upstream product development strategies that utilize smaller-scale processes cannot adequately eliminate clonal predisposition toward toxic lactate accumulation in the production stage. This is, in part, because cellular features that predispose Chinese Hamster Ovarian (CHO) cells to lactate overproduction in the production-scale process remain undefined. We have implemented a proteomics strategy to characterize the molecular features of CHO cells with a propensity to accumulate toxic levels of lactate during bioproduction. Mimicking industrial scale toxic lactate accumulation, we have isolated a clone that reproducibly overproduces lactate in a 10L scale processes, but not in smaller vessels. Deep proteomics profiling of this high-lactate clone relative to another displaying typical lactate profiles during bioproduction was performed using the Bruker timsToF HT platform and DIA-PASEF to quantify over 9000 proteins over a 10-day production process. We further performed spatial proteomic to interrogate the subcellular distribution of proteins in high and low lactate CHO clones. We observed that high-lactate cells are predisposed to mitochondrial dysfunction that may be linked to lactate overproduction. All together, we have uncovered proteomic features that may predict toxic lactate accumulation in the production setting, which may be utilized to inform host development efforts.
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