(12am) Understanding and Improving Biomanufacturing in Chinese Hamster Ovary Cells through New Gene Expression and Systemic Cell Engineering Platforms

My research experience has focused on the various subjects of Chinese hamster ovary (CHO) cells, such as -omics studies (genomics, transcriptomics, and proteomics), cytogenetics, genome and metabolic engineering, and bioprocess engineering. CHO cells are the most important mammalian host cells for the biomanufacturing of therapeutic proteins, accounting for more than 50% of global annual biopharmaceutical protein sales. In addition, transformative changes in CHO cell line development are required to meet industrial demands, such as lowering manufacturing cost, producing new medicines, and extending culture duration. I plan to continue this work towards improving CHO biomanufacturing platforms.
While significant productivity improvements have been achieved by extensive efforts over three decades, understanding of CHO biology has been limited. For example, what makes a high productivity cell line, how media components/supplements affect culture longevity and productivity, and how stressful culture conditions (low culture temperature, hyperosmolality, or histone deacetylase inhibitor treatment) can lead to higher recombinant protein production are still largely unknown. In addition, although cell line instability issues, such as unexpected changes in productivity, product quality, and host cell protein (HCP) expression, are increasingly recognized to negatively affect biomanufacturing processes, the causes and underlying mechanisms of cell line instability remain poorly understood. Addressing these important questions and challenges will enable us to develop stable, well characterized CHO cell lines producing proteins and biomolecules with desirable quality attributes, thereby providing more effective, better controlled, and safer therapeutics for human health. Therefore, my research interests include (1) developing new gene expression and amplification methods for the stable and high production of therapeutic proteins and (2) mammalian genome and cell engineering based on genome scale modeling and systems biology.

Postdoctoral Projects:

â??Knocking out CHO host cell proteins using CRISPR/Cas9 to improve downstream processesâ? and â??Developing a karyotype-based framework to identify and quantify CHO cellsâ?? genomic/chromosomal instability that affects protein productivityâ? under the supervision of Dr. Kelvin Lee at the University of Delaware.
â??Metabolic and bioprocess engineering of CHO cells to produce bioengineered heparinâ? under the supervision of Dr. Susan Sharfstein at SUNY Polytechnic Institute and Dr. Robert Linhardt at Rensselaer Polytechnic Institute.

Ph.D. Dissertation:

â??Engineering of recombinant Chinese hamster ovary cells using a proteomic approachâ? under the supervision of Dr. Gyun Min Lee at Korea Advanced Institute of Science and Technology (KAIST).

Education:

Ph.D., Biological Sciences, KAIST, 2009
B.S., Biological Sciences, KAIST, 2003

Selected Publications:

1. Baik JY, Lee KH. 2016. Toward improved host cell protein impurity assessment. Biotechnol. J. 11(8):998-999.
2. Baik JY, Dahodwala H, Oduah E, Talman L, Gemmill TR, Gasimli L, Datta P, Yang B, Li G, Zhang F, Li L, Linhardt RJ, Campbell AM, Gorfien SF, Sharfstein ST. 2015. Optimization of bioprocess conditions improves production of a CHO cell-derived, bioengineered heparin. Biotechnol. J. 10(7):1067-1081.
3. Baik JY, Lee KH. 2014. Toward product attribute control: Developments from genome sequencing. Curr. Opin. Biotechnol. 30:40-44.
4. Baik JY, Gasimli L, Yang B, Datta P, Zhang F, Glass CA, Esko JD, Linhardt RJ, Sharfstein ST. 2012. Metabolic engineering of Chinese hamster ovary cells: Towards a bioengineered heparin. Metab. Eng. 14(2):81-90.
5. Baik JY, Ha TK, Kim YH, Lee GM. 2011. Proteomic understanding of intracellular responses of recombinant chinese hamster ovary cells adapted to grow in serum-free suspension culture. Biotechnol. Prog. 27(6):1680-1688.

Teaching Interests:

Learning with understanding: Learning is more than just memorizing and practicing; it is about understanding. Through all my teaching and mentoring experience, I challenged my studentsâ?? critical thinking skills by asking questions, such as what each procedure meant, why it was necessary, and which steps were more critical than others, and by asking them to explain their thought process. Through classes, I will continually emphasize learning with understanding by asking â??how can we understand this concept?â?.

Applicability: As an engineer, I seek to link knowledge to applications. I will provide a platform for students to translate knowledge gleaned from lectures to problems or applications in various engineering fields.
Communication: As collaboration and interdisciplinary research become increasingly important, good communication skills are essential to successful research. Moreover, strong written and verbal skills are critical to convey the importance and impact of research. To improve communication skills, I will foster discussion-oriented class environments, which will also complement my learning with understanding philosophy. In addition to scientific communication skills, I will also pursue outreach activities to connect research to real life in various ways, such as hands-on activities, demonstrations, or engaging tours of labs/facilities. In conclusion, I believe that when we are able to understand, apply, and propagate what we learn, knowledge becomes alive and inspires future scientists and engineers.

I would apply my teaching principles to undergraduate and graduate courses, including Molecular Biology, Biochemistry, Genetics, Bioprocess Engineering, and Biotechnology. I am also interested in developing advanced cutting-edge courses such as Genomics, Genome Engineering, and Recent Progress in Biochemical Engineering and Technology.