Assistant Professor, Department of Chemical and Biological Engineering
Rensselaer Polytechnic Institute

Education:
Ph.D., Chemical Engineering, University of California, Berkeley, 1993
B.S., Chemical Engineering, with Honors, California Institute of Technology, 1987

Career Highlights:
After receiving her doctorate degree in 1993, Sharfstein received a three-year National Institutes of Health (NIH) postdoctoral fellowship to perform research first at the University of California, Berkeley and then at the University of California, Los Angeles (UCLA) Medical School. She joined Rensselaer in 2001 after serving on the faculty at the University of Toledo for five years and spending a year as a visiting scientist at the New York State Department of Health Wadsworth Laboratories. Sharfstein also was a visiting assistant professor at the Center for Cell Biology and Cancer Research at Albany Medical College in 2001.

Sharfstein received a five-year National Science Foundation (NSF) Early Career Development (CAREER) Award in 2000 for her work on hybridoma cells and was nominated for the Outstanding Teacher Award at the University of Toledo during the 1997-’98 school year. A publication she co-authored on the imaging of gene expression in mice was awarded third place for Outstanding Basic Science Investigations for 1998 by the Journal of Nuclear Medicine.

Her many speaking engagements have included talks at the University of Rochester, the University of Southern California, and the University of Nebraska, as well as at industrial sites such as the General Electric Global Research Center. Sharfstein’s professional contributions include serving as a panelist for several divisions of the NSF and as an active member of organizations such as the American Chemical Society and the American Institute of Chemical Engineers.

Research Areas:
The focus of Sharfstein’s research is on gene expression and recombinant protein production for bioprocessing. She uses tools of cell and molecular biology to develop a fundamental understanding of cell culture systems in order to improve productivity and product quality.

The first of her two main projects involves using stress to increase antibody production in hybridoma cells grown in culture. Hybridomas are being used to produce monoclonal antibodies, which are used for a variety of applications, including diagnostic kits and devices, protein separations, and research applications. Monoclonal-antibodies can detect diseases such as hepatitis B, as well as a wide variety of other conditions, including pregnancy, allergies, and drug use. Several researchers have shown that a substantial increase in specific antibody production (production per cell) occurs in hybridoma cell lines in response to hyperosmotic stress. Sharfstein discovered a similar effect when she subjected cells to a “metabolic stress” by reducing the extracellular glutamine. She hopes to gain an understanding of the mechanism by which these stresses improve antibody production in order to yield insight into the rate-limiting steps in antibody synthesis and secretion.

Her other major project involves the role of cell adhesion and cytoskeleton on expression of recombinant proteins from cultured mammalian cells, primarily Chinese hamster ovary (CHO) cells. CHO cells are by nature adherent; however, to simplify processing conditions, they are often forced to grow free-floating in suspension. Culture in suspension would call for a change in cell-cell and cell-substrate interactions, as well as modification of the cytoskeleton. There are many reports in the literature of the effect of cytoskeletal elements and cell shape on gene expression, but only a single paper addressing this area with regard to production of biological materials from cultured cells. This is particularly important for recombinant glycoproteins where glycosylation can play a critical role in activity, immunogenicity, and clearance rates. For CHO cells making recombinant tissue plasminogen activator (t-PA), Sharfstein’s group has demonstrated significant differences in productivity for cells free-floating in suspension or grown attached to tissue culture plastic or to microcarrier beads.

Sharfstein is also collaborating with Harry Bungay, Rensselaer professor of chemical engineering, to extend her expertise into microbial work.

Selected Publications:
Z. Sun, R. Zhou, S. Liang, K.M. McNeeley, and S.T. Sharfstein, “Hyperosmotic Stress in Murine Hybridoma Cells: Effects on Antibody Transcription, Translation, Posttranslational Processing, and the Cell Cycle,” Biotechnology Progress, 20, 576-589, (2004).

S.T. Sharfstein, R. Zhou, and Z. Sun, “Regulation of Antibody Production in Hybridoma Cells: Role of Transcription, Translation and Post-Translational Processing,” Abstracts of Papers of the American Chemical Society, 224, 076-BIOT, Part 1, (2002).

S. Sharfstein and P. Relue, “Biotechnology and Bioprocessing Laboratory for Chemical Engineering and Bioengineering,” Proceedings of the 2001 American Society for Engineering Education Annual Conference & Exposition, (2001).

J. Faghihi, X. Jiang, R. Vierling, S. Goldman, S. Sharfstein, J. Sarver, and P. Erhardt, “Reproducibility of the High-Performance Liquid Chromatographic Fingerprints Obtained from Two Soybean Cultivars and a Selected Progeny,” Journal of Chromatography A, 915, 61-74, (2001).

D.C. MacLaren, S.S. Gambhir, N. Satyamurthy, J.R. Bario, S. Sharfstein, T. Toyokuni, L. Wu, A.J. Berk, S.R. Cherry, M.E. Phelps, and H.R. Herschman, “Repetitive, Non-Invasive Imaging of the Dopamine D2 Receptor as a Reporter Gene in Living Animals,” Gene Therapy, 6, 785-791, (1999).

A. Mancuso, S.T. Sharfstein, E.J. Fernandez, D.S. Clark, and H.W. Blanch, Effect of Extracellular Glutamine Concentration Primary and Secondary Metabolism of a Murine Hybridoma: An In Vivo 13C Nuclear Magnetic Resonance Study, Biotechnology and Bioengineering, 57, (2), 172-186, (1998).

S.S. Gambhir, J.R. Barrio, L. Wu, M. Iyer, M. Namavari, N. Satyamurthy, C. Parrish, D.C. MacLaren, A.R. Borghei, E. Bauer, L.A. Green, S.T. Sharfstein, A.J. Berk, S.R. Cherry, M.E. Phelps, and H.R. Herschman, “Imaging of Adenoviral Directed Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene Expression in Mice with Ganciclovir,” Journal of Nuclear Medicine, 39, 2003-2011, (1998).

H.R. Herschman, S. Sharfstein S.S. Gambhir, D.C. MacLaren, S. Cherry, A. Srinivasan, N. Satyamurthy, J.R. Barrio, and M.E. Phelps, “In Vivo Imaging of Gene Expression Associated with Cell Replication,” Journal of Nuclear Medicine, 38, 1056, (1997).

S.T. Sharfstein, S.J. Van Dien, and J.D. Keasling, “Modulation of the Phosphate-Starvation Response in Escherichia coli by Genetic Manipulation of the Polyphosphate Pathways,” Biotechnology and Bioengineering, 51, (4), 434-437, (1996).

S.T. Sharfstein, S.N. Tucker, A. Mancuso, H.W. Blanch, and D.S. Clark, “Quantitative In Vivo NMR Studies of Hybridoma Metabolism,” Biotechnology and Bioengineering, 43, (11), 1059-1074, (1994).

Contact Information:
Susan Sharfstein
(518) 276-2166
sharfs@rpi.edu
http://www.eng.rpi.edu/soe/directory_faculty_details.cfm?facultyID=sharfs