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Research

Diabetes and Obesity

An integrated network approach to understand in vivo metabolism in health and disease

Control of nutrient metabolism is distributed across a network of interacting tissues and organs. This metabolic crosstalk, however, can become dysfunctional in conditions such as diabetes and obesity. Our lab uses metabolic tracers to quantify the flow of metabolites within and between organ systems to better understand the burden of metabolic disease and identify potential targets for intervention. We couple these in vivo projects with in vitro systems to isolate mechanisms of cellular metabolic dysfunction from the global impact of overnutrition.

 

Cell Culture Engineering

Engineering mitochondrial metabolism as a strategy to maximize IgG production

We are aiming to engineer CHO metabolism to promote mitochondrial respiration and TCA cycle flux specifically during the stationary phase, in order to minimize negative impacts on culture growth during the exponential phase. [Read more]

Selected publications:

  1. S. A. Sacco, A. G. McAtee, I. Trenary, K. D. Smith, M. J. Betenbaugh, J. D. Young. Overexpression of peroxisome proliferator-activated receptor co-activator-1α (PGC-1α) in Chinese hamster ovary cells increases oxidative metabolism and IgG productivity. Metabolic Engineering 79:108-117, 2023.
  2. S. A. Sacco, A. M. Tuckowski, I. Trenary, L. Kraft, M. J. Betenbaugh, J. D. Young, K. D. Smith*. Attenuation of glutamine synthetase selection marker improves product titer and reduces glutamine overflow in Chinese hamster ovary cells. Biotechnology and Bioengineering 119:1712–1727, 2022.

 

 

 

Photosynthesis Research

Understanding metabolism of photosynthetic organisms

We apply 13C flux analysis to quantify metabolic phenotypes of plants, cyanobacteria and diatom in response to genetic perturbations and environmental changes. [read more]

Selected Publications:
1. F Ma, LJ Jazmin, JD Young, DK Allen. Isotopically nonstationary 13C flux analysis of changes in Arabidopsis thaliana leaf metabolism due to high light acclimation. 2014. Proceedings of the National Academy of Sciences 111 (47), 16967-16972

Enhancing metabolic flux to photosynthetic bioproducts

We are applying 13C flux analysis and metabolic engineering to redirect carbon flux toward biofuels, nutrients, and chemicals in engineered strains of cyanobacteria. [read more]

Selected Publications:

  1. B Wang, C Zuniga, MT Guarnieri, K Zengler, M Betenbaugh, JD Young. Metabolic engineering of Synechococcus elongatus 7942 for enhanced sucrose biosynthesis. 2023. Metabolic Engineering 80, 12-24
  2. YE Cheah, Y Xu, SA Sacco, PK Babele, AO Zheng, CH Johnson, …Systematic identification and elimination of flux bottlenecks in the aldehyde production pathway of Synechococcus elongatus PCC 7942. 2020. Metabolic engineering 60, 56-65
  3. LJ Jazmin, Y Xu, YE Cheah, AO Adebiyi, CH Johnson, JD Young. Isotopically nonstationary 13C flux analysis of cyanobacterial isobutyraldehyde production. 2017. Metabolic engineering 42, 9-18

Extracellular Vesicle Biomanufacturing

Scalable Stem Cell-Based (iPSCs) Platform to Produce Tissue-Specific Extracellular Vesicles (EVs)

We are applying scalable biomanufacturing strategies to STEM cell growth conditions to increase extracellular vesicle production.