07/11/2023
By Danielle Fretwell

The Francis College of Engineering, Department of Chemical Engineering, invites you to attend a Doctoral Dissertation defense by Duc Hoang on "oupling LC-MS with Targeted CHO Cells Metabolism Study: Developing Platform, Identifying Bottlenecks, and Modeling Strategy towards Improving Critical Process Performance in CHO Bioprocess."

Candidate Name: Duc Hoang
Degree: Doctoral
Defense Date: July 19, 2023
Time (from/to): 10 a.m. to noon
Location: UCC415

Committee:

Advisor: Seongkyu Yoon, Professor, Department of Chemical Engineering, University of Massachusetts Lowell

Committee Members:

  • Subash Sharma, Professor, Chemical Engineering, University of Massachusetts Lowell
  • Dongming Xie, Professor, Chemical Engineering, University of Massachusetts Lowell
  • Dhimiter Bello, Professor, College of Health and Sciences, University of Massachusetts Lowell
  • Delia Lyons, Principal Scientist, Principal Scientist, AbbVie Bioresearch and Biocenter, AbbVie Pharmac

Brief Abstract :

Recent advances in bioprocessing and cell line engineering allowed substantial improvements bioprocess, with CHO cell densities reaching over 20 million cells per milliliter in fed-batch and perfusion cell culture systems. However, higher cell densities come with adverse effects on titer yield and quality, which poses a challenge for biomanufacturing processes in lifting titer productivity to a higher ceiling. Additionally, detailed knowledge on cell physiology and particularly at the level of cellular metabolism is often lacking due to inability to predict CHO cellular metabolism during various stages of cell culture. CHO metabolism, characterized by high uptake rates of supplemented nutrients of carbon and nitrogen-derived substrates, is inefficient and suboptimal. Previous studies have shown that CHO metabolism is poorly regulated, which prevents the cells to fully utilize nutrients to support growth and proteins production. Instead, significant fractions of fed glucose and amino acids are diverted to generation of metabolic by-products through different amino acid metabolism pathways. Cells grown in fed batch processes consume many nutrients that do not support titer production and adversely pose a risk of compromised glycosylation profiles. It has been shown that accrual of waste by-products (such as ammonia) can alter the glycosylation profile of recombinant proteins. Omics approaches often are singular, which only study key metabolite reactions in defined metabolic pathways (such as metabolism of amino acids, glycolysis, metabolism of central carbon, etc.) and have limitations in identifying novel pathway interactions. This thesis proposal sought to develop and apply metabolomics analysis to identify bottlenecks in CHO cells culture, developing tools to remedy such bottlenecks, and apply obtained knowledge to improve key performance indicator in a bioprocess. The platform as developed through this thesis aims to unraveling the identities of the involved metabolic pathways and intracellular interactions between metabolites using multifaceted approaches in metabolomics studies of mammalian cells, with the goal to improving key process attributes in a standard bioprocess.