03/10/2026
By Danielle Fretwell

The Francis College of Engineering, Department of Biomedical Engineering and Biotechnology, invites you to attend a Doctoral Dissertation Proposal defense by Hourieh Ahi on: "Mechanistic Control of Mammalian Cell Productivity for Improved Viral Vector and Recombinant Protein Biomanufacturing."

Candidate Name: Hourieh Ahi
Degree: Doctoral
Defense Date: Wednesday, March, 18, 2026
Time: 10 a.m. - noon
Location: Perry 315

Committee:

  • Advisor: Seongkyu Yoon, PhD, Professor, Chemical Engineering, University of Massachusetts Lowell
  • David McNally, PhD, Assistant Professor, Medicine, UMass Chan Medical School
  • Dan Wang, PhD, Assistant Professor, Genetic and Cellular Medicine, UMass Chan Medical School
  • Madhuresh Sumit, PhD, Associate Director, Genomic Medicine, Sanofi
  • Xingwei Wang, PhD, Professor, Electrical & Computer Engineering, University of Massachusetts Lowell

Abstract:
Mammalian cell platforms such as HEK293 and Chinese hamster ovary (CHO) cells are central to modern biopharmaceutical manufacturing, yet important biological and process-level barriers still limit productivity and product quality. HEK293 cells are widely used for recombinant adeno-associated virus (rAAV) vector production for gene therapy, but current transient transfection-based processes remain constrained by modest yields, variable vector quality, and limited mechanistic understanding of how medium composition influences production outcomes. In particular, amino acids are critical regulators of metabolism, stress responses, and biosynthesis, yet their specific contributions to rAAV genome yield and capsid quality remain poorly defined. In parallel, emerging evidence suggests that chromatin regulation of episomal production plasmids may represent an additional constraint on rAAV productivity, but the link between amino acid availability, metabolic state, and chromatin-mediated transcription during vector production is not well understood. Beyond viral vector manufacturing, CHO-based recombinant protein production is also limited by the growth–productivity trade-off, where rapid proliferation often conflicts with high cell-specific productivity, and the molecular regulators governing transitions between growth-dominant and production-dominant states remain incompletely defined.

This proposal seeks to establish a mechanistic framework for improving mammalian cell productivity by integrating nutrient regulation, chromatin biology, and cellular state transitions. Aim 1 will maximize rAAV yields and define the role of amino acids through design-of-experiments–based optimization of AMBIC.293 medium. Aim 2 will determine how amino acid availability regulates chromatin programs during rAAV production by examining transcriptional output and chromatin-associated features of episomal production templates under baseline and optimized conditions. Aim 3 will identify and validate metabolic and transcriptional biomarkers that regulate the transition between growth and productivity in CHO cells using integrated transcriptomic and metabolomic analyses. Together, these studies are expected to generate interpretable amino-acid design rules for rAAV manufacturing, reveal mechanistic links between metabolism and chromatin regulation during transient vector production, and identify actionable biomarkers for improving CHO productivity.