Dr. Susan Sharfstein, Associate Professor of Nanoscale Science and Engineering at SUNY Polytechnic Institute, and a speaker at the upcoming Optimizing Cell Line Development conference shares insight on her presentation "Epigenetic Effects on Antibody Production in CHO Cells".

Q. How do these insights affect strategies for cell line development?

What we hope to understand is when you are doing cell line selection, are there markers that you should look for beside growth and productivity that might identify why some candidates might have more long term stability or show improved expression as you go to process scale.

Q. What causes the difference in transcription factor binding between parental cell lines and DHFR-amplified progeny?

That is the $64,000 question. We have a couple of hypotheses. One of them is changes in DNA methylation state either between different families or during the amplification process. The other question is whether or not you get higher levels of expression or activation of the transcription factors upon amplification. I am currently writing a sabbatical proposal to spend a couple of months in Ireland at Dublin City University working with their CHO proteomics group to look at the second issue.

Q. What are you most looking forward to at The Bioprocessing Summit?

I try when I go to these conferences to hear something that I don’t know much about but would like to learn more. I am going to try to attend some of the sessions on cell and gene therapies. I think that they have reached the point of scientific/clinical potential that the engineering of “large-scale” cultures (probably 10’s to 100’s of liters) is going to become necessary. I would like to learn what the underlying process needs are to make this feasible.


Epigenetic Effects on Antibody Production in CHO Cells

Identifying characteristics of high productivity cell clones is critical for rapid cell line development. We evaluated epigenetic differences between parental clones and DHFR-amplified progeny including transcription factor activation and DNA methylation. These studies suggest that transcription factor binding is altered in different families of parental cell lines and progeny, providing possible strategies for cell line engineering.
How is transcription factor binding altered in different families of parental cell lines and progeny?
We compared two different families of parental cell lines and amplified progeny. In one cell line, we oberved an increase in the binding of cAMP response element-binding protein (CREB)to the CMV promoter in the amplified parental cell lines and in the other family we observed an increase in NF kappa B binding to CMV in the amplified cell lines compared to the parental.

To learn more about this presentation and The Bioprocessing Summit, visit Bioprocessingsummit.com/Cell-Line-Development

Susan Sharfstein received her B.S. in chemical engineering with honors from Caltech in 1987 and her Ph.D. in chemical engineering from UC Berkeley in 1993, receiving graduate fellowships from the university and the National Science Foundation. She received a National Institutes of Health Individual Research Service Award to pursue postdoctoral studies, initially at UC Berkeley and subsequently at the UCLA Medical School. Dr. Sharfstein joined the faculty at the University of Toledo in Bioengineering in 1996. In 2000, she received a National Science Foundation POWRE award to study glycobiology at the New York State Department of Health Wadsworth Laboratories.
In 2001, she joined the Department of Chemical and Biological Engineering at Rensselaer Polytechnic Institute and in 2007 she received a dual appointment in Biology. In 2010, she joined the faculty at the SUNY Polytechnic Institute, Collegse of Nanoscale Science and Engineering as an Associate Professor of Nanobioscience. Professor Sharfstein received an NSF CAREER grant in 2000 for her work on hyperosmotic stress responses of hybridoma cells and the School of Engineering Education Excellence Award and the Class of 1951 Outstanding Teaching Award in 2007. Professor Sharfstein’s research interests include mammalian and microbial cell bioprocessing, control of protein glycosylation, metabolic engineering, biosensing, and development of systems for high-throughput screening of nucleic acids and small molecules. She is the author of nearly 50 papers and book chapters in the fields of biotechnology and bioprocessing.

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