Listen to Professor Sharfstein discuss using nanoparticles for gene delivery in 3D cell assays on the August 2010 ACS Nano podcast

Education

• Ph.D. in Chemical Engineering, University of California, Berkeley, 1993

• B.S. with honors in Chemical Engineering, California Institute of Technology, Pasadena, CA, 1987

Honors and Awards

• Fulbright Global Scholar Award, 2017-18
• Biotechnology Subject Editor, Elsevier Life Science Reference Module, 2015-
• SUNY Research Foundation Faculty Fellow, 2015-16
• Marquis Who's Who in America, 2010
• RPI Class of '51 Outstanding Teaching Award, 2007
• RPI School of Engineering Excellence in Education Award, 2007
• CAREER: National Science Foundation Early Career Development Award, 2000
• Inducted into Sigma Xi at University of Toledo, 1997
• National Institutes of Health Postdoctoral Fellowship, 1993

Description of research

The focus of the research in the Sharfstein laboratory is on understanding the role of culture conditions and cell physiology on use of living systems for industrially relevant processes. Our primary area of interest is the use of mammalian cell systems for the production of therapeutic proteins and carbohydrates. We use the tools of modern cell and molecular biology along with “omics” to probe physiological states, with an objective of optimizing production systems both from an engineering perspective (e.g. culture conditions) as well as from a biological perspective (cellular and metabolic engineering). Current projects are focused on the production of heparin (a critically important anticoagulant drug) in Chinese hamster ovary (CHO) cells, characterizing CHO cell clones producing recombinant monoclonal antibodies to identify factors that affect productivity, the effects of osmolarity on monoclonal antibody production in CHO cells, and the effects of growth rate on cell physiology in Escherichia coli. 

We are also interested in developing new tools using nanotechnology to better understand cultured cells and bioprocesses. Current projects are focused on patterning cells on surfaces for high throughput delivery of silencing RNA and development of novel biosensors for use in bioreactors.

Publications

H. Dahodwala, P. Kaushik, V. Tejwani, C.-C. Kuo, P. Menard, M. Henry, B.G. Voldborg, N. E. Lewis, P. Meleady, and S.T. Sharfstein, Increased mAb production in amplified CHO cell lines is associated with increased interaction of CREB1 with transgene promoter, Current Research in Biotechnology, 1: 49-57 (2019) doi: 10.1016/j.crbiot.2019.09.001

S. Li, S.W. Cha, K. Heffner, D. Baycin-Hizal, M. Bowen, R. Chaerkady, R. Cole, V. Tejwani, P. Kaushik, M. Henry, P. Meleady, S.T. Sharfstein, M.J. Betenbaugh, V. Bafna, N.E. Lewis, Proteogenomic annotation of the Chinese hamster reveals extensive novel translation events and endogenous retroviral elements. Journal of Proteome Research, 2019 Apr 25. doi: 10.1021/acs.jproteome.8b00935.

B.E. Thacker and S.T. Sharfstein, Metabolic Engineering of Mammalian Cells to Produce Heparan Sulfates, Emerging Topics in Life Sciences, 2 (3) 443-452 (2018) DOI: 10.1042/ETLS20180007

+V. Tejwani, M.R. Andersen, J-H. Nam, and S.T Sharfstein, Glycoengineering in CHO cells: Advances in systems biology, Biotechnology Journal 13(3):e1700234 (2018) DOI: 10.1002/biot.201700234 Featured on inside back cover and one of the most read papers in the journal issue

S.T. Sharfstein, Non-protein biologic therapeutics, Current Opinion in Biotechnology 53: 65-75 (2018) doi: 10.1016/j.copbio.2017.12.014

*J.J. Terracina, S.T. Sharfstein, M. Bergkvist, In Silico characterization of Enantioselective Molecularly Imprinted Binding Sites, Journal of Molecular Recognition, 31: e2612 (2018) doi: 10.1002/jmr.2612

S. Zhang, ^D.E. Speed, ^S.R. Trammell, and S.T. Sharfstein, Reactivity of Deposited Byproducts Generated from ZrO2 Atomic Layer Deposition, Journal of Loss Prevention in the Process Industries, 45: 78-87 (2017) doi: 10.1016/j.jlp.2016.11.008

*K.Y. Torrejon, #E.L. Papke, #J.R. Halman, M. Bergkvist, J. Danias, S.T. Sharfstein, and Y. Xie, TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a Rho-associated kinase inhibitor, Scientific Reports, 6: 38319 (2016) doi:10.1038/srep38319

*E. Oduah, R.J. Linhardt, and S.T. Sharfstein, Heparin: Past, Present, and Future, Pharmaceuticals, 9: 38 (2016) doi:10.3390/ph9030038

*J.J. Terracina, S.T. Sharfstein, and M. Bergkvist, Computational Investigation of Stoichiometric Effects, Binding Site Heterogeneities, and Selectivities of Molecularly Imprinted Polymers, Journal of Molecular Modeling, 22: 139 (2016) doi: 10.1007/s00894-016-3005-1

*K.Y. Torrejon, E.L. Papke, #J.R. Halman, J. Stolwijk, *C.N. Dautriche, M. Bergkvist, J. Danias, S.T. Sharfstein, and Y. Xie, Bioengineered Glaucomatous 3D Human Trabecular Meshwork as an in vitro Disease Model, Biotechnology and Bioengineering, 113: 1357-68 (2016) doi:10.1002/bit.25899

*C.N. Dautriche, Y. Tian, Y. Xie, and S.T. Sharfstein, A Closer Look at Schlemm’s Canal Cell Physiology: Implications for Biomimetics, Journal of Functional Biomaterials, 6: 963-985 (2015) doi:10.3390/jfb6030963

*C.N. Dautriche, #D. Szymanski, #M. Kerr, *K.Y. Torrejon, M. Bergkvist, Y. Xie, J. Danias, W.D. Stamer, and S.T. Sharfstein, A biomimetic Schlemm's canal inner wall: A model to study outflow physiology, glaucoma pathology and high-throughput drug screening, Biomaterials 65: 86-92 (2015) doi:10.1016/j.biomaterials.2015.06.034

+J-Y Baik, +H. Dahodwala, *E. Oduah, #L. Talman, T.R. Gemmill, *P. Datta, *L. Gasimli, B. Yang, G. Li, F. Zhang, L. Li, R.J. Linhardt, ^A.M. Campbell, ^S.F. Gorfien, and S.T. Sharfstein, Optimization of bioprocess conditions improves production of a CHO cell-derived, bioengineered heparin, Biotechnology Journal, 10: 1067–1081 (2015) DOI 10.1002/biot.201400665

*M. Mason, ^B. Sweeney, ^K. Cain, ^P. Stephens, and S.T. Sharfstein, Reduced Culture Temperature Differentially Affects Expression and Biophysical Properties of Monoclonal Antibody Variants, Antibodies, 3: 253-271 (2014) doi:10.3390/antib3030253

+H. Dahodwala and S.T. Sharfstein, Role of epigenetics in expression of recombinant proteins from mammalian cells, Pharmaceutical Bioprocessing, 2:403-419 (2014) DOI: 10.4155/PBP.14.47

*C.N. Dautriche, Y. Xie, and S.T. Sharfstein, Walking through Trabecular Meshwork Biology: Towards Engineering Design of Outflow Physiology, Biotechnology Advances, 32(5): 971-983 (2014) DOI: 10.1016/j.biotechadv.2014.04.012

*L. Gasimli, C.A. Glass, *P. Datta, B. Yang, G. Li, T.R. Gemmill, +J-Y. Baik, S.T. Sharfstein, J.D. Esko, and R.J. Linhardt, Bioengineering murine mastocytoma cells to produce anticoagulant heparin, Glycobiology, 24 (3): 272-280 (2014) doi:10.1093/glycob/cwt108

*P. Datta, B. Yang, R J. Linhardt, and S.T. Sharfstein, Modulation of heparan sulfate biosynthesis by sodium butyrate in recombinant CHO cells. Cytotechnology, 67: 223-235 (2015) DOI 10.1007/s10616-013-9677-9

*P. Datta, L. Meli, L. Li, ^N. Migliore, ^E. Schaefer, S.T. Sharfstein, J.S. Dordick, and R.J. Linhardt, Microarray platform affords improved product analysis in mammalian cell growth studies. Biotechnology Journal, 9: 386–395 (2014), DOI: 10.1002/biot.201300288

*P. Datta, G. Li, B. Yang, X. Zhao, +J-Y. Baik, T.R. Gemmill, S.T. Sharfstein, and R.J. Linhardt, Bioengineered Chinese hamster ovary cells with Golgi-targeted 3-O-sulfotransferase-1 biosynthesize heparan sulfate with an antithrombin binding site, Journal Biological Chemistry 288: 37308-37318 (2013) doi: 10.1074/jbc.M113.519033

*K.Y. Torrejon, D. Pu, M. Bergkvist, J. Danias, S.T. Sharfstein, and Y. Xie, Recreating a Human Trabecular Meshwork Outflow System on Microfabricated Porous Structures. Biotechnology and Bioengineering, 110: 3205–3218 (2013) DOI: 10.1002/bit.24977

P. Datta, R.J. Linhardt, and S.T. Sharfstein, An ‘Omics Approach Towards CHO Cell Engineering. Biotechnology and Bioengineering, 110: 1255–1271 (2013) DOI: 10.1002/bit.24841

J-Y. Baik, C. L. Wang, B. Yang, R. J. Linhardt and S. T. Sharfstein, Toward a bioengineered heparin: Challenges and strategies for metabolic engineering of mammalian cells. Bioengineered 3: 225 - 229 (2012). http://doi.org/10.4161/bioe.20902

H. Zhang, M.-Y. Lee, M. G. Hogg, J. S. Dordick, and S. T. Sharfstein, High-Throughput Transfection of Interfering RNA into a 3D Cell-Culture Chip. Small, 8: 2091–2098. (2012) doi: 10.1002/smll.201102205

M. Mason, B. Sweeney, K. Cain, P. Stephens, and S.T. Sharfstein, Identifying bottlenecks in transient and stable production of recombinant monoclonal-antibody sequence variants in Chinese hamster ovary cells, Biotechnology Progress, 28: 846–855. (2012) DOI: 10.1002/btpr.1542

J-Y. Baik, L. Gasimli, B. Yang, P. Datta, F. Zhang, C.A. Glass, J.D. Esko, R.J. Linhardt, and S.T. Sharfstein, Metabolic engineering of Chinese hamster ovary cells: Towards a bioengineered heparin, Metabolic Engineering, 14: 81–90. (2012). doi.org/10.1016/j.ymben.2012.01.008

H. Dahodwala, M. Nowey, T. Mitina, and S.T. Sharfstein, Effects of Clonal Variation on Growth, Metabolism, and Productivity in Response to Trophic Factor Stimulation: A Study of Chinese Hamster Ovary Cells Producing a Recombinant Monoclonal Antibody, Cytotechnology, 64:27–41 (2012). DOI: 10.1007/s10616-011-9388-z

B. Yang, A. Weyers, J-Y. Baik, E. Sterner, S. Sharfstein, S.A. Mousa, F. Zhang, J.S. Dordick, R. J. Linhardt, Ultraperformance ion-pairing liquid chromatography with on-line electrospray ion trap mass spectrometry for heparin disaccharide analysis, Analytical Biochemistry, 415: 59-66 (2011). doi:10.1016/j.ab.2011.04.003

T.R. Kiehl, D. Shen. S.F. Khattak, Z. Lee, and S.T. Sharfstein, Observations of cell-size dynamics under osmotic stress, Cytometry Part A 79A: 560-569 (2011), doi:10.1002/cyto.a.21076

A.C. Baughman, S.T. Sharfstein, and L.L. Martin, A Flexible State-space Approach for the Modeling of Metabolic Networks I: Development of Mathematical Methods, Metabolic Engineering, 13: 125-137 (2011). doi:10.1016/j.ymben.2010.12.002

A.C. Baughman, S.T. Sharfstein, and L.L. Martin, A Flexible State-space Approach for the Modeling of Metabolic Networks II: Advanced Interrogation of Hybridoma Metabolism, Metabolic Engineering, 13: 138-149 (2011). doi:10.1016/j.ymben.2010.12.003

H. Zhang, M-Y. Lee, M.G. Hogg, J.S. Dordick, and S.T. Sharfstein, Gene delivery in three-dimensional cell cultures by superparamagnetic nanoparticles, ACS Nano, 4: 4733–4743 (2010). http://pubs.acs.org/doi/abs/10.1021/nn9018812

D. Shen, T. R. Kiehl, S.F. Khattak, Z. Li, A. He, I.M. Neuhaus, P.S. Kayne, V. Patel, and S. T. Sharfstein, Transcriptomic Responses to Osmotic Stress: A Study of Industrial Fed-Batch CHO Cell Cultures, Biotechnology Progress, 26: 1104-1115 (2010). http://www3.interscience.wiley.com/journal/123276644/abstract

A.C. Baughman, X. Huang, S.T. Sharfstein, and L.L. Martin, On the Dynamic Modeling of Mammalian Cell Metabolism and mAb Production, Computers in Chemical Engineering, 34: 210-222 (2010). doi:10.1016/j.compchemeng.2009.06.019

J.H. Nam, M. Ermonval, and S.T. Sharfstein, The effects of microcarrier culture on recombinant CHO cells under biphasic hypothermic culture conditions, Cytotechnology, 59: 81-91 (2009). DOI: 10.1007/s10616-009-9196-x

S. Barua, S, A. Joshi, A. Banerjee, D. Matthews, S. T. Sharfstein, S. Cramer, R. Kane, K. Rege, Parallel Synthesis and Screening of Polymers for Non-Viral Gene Delivery, Molecular Pharmaceutics, 6: 86-97 (2009). http://pubs.acs.org/doi/abs/10.1021/mp800151j

Z. Jiang and S.T. Sharfstein, Characterization of gene localization and accessibility in DHFR-amplified CHO cells,  Biotechnology Progress, 25: 296-300 (2009). http://www3.interscience.wiley.com/journal/121634088/abstract

J.H. Nam, F.Zhang, R.J. Linhardt, and S.T. Sharfstein, Effects of culture conditions on the glycosylation of SEAP produced by rCHO cells in a controlled bioreactor:  Biotechnology and Bioengineering, 100: 1178-1192 (2008). http://www3.interscience.wiley.com/journal/117928542/abstract

S.T. Sharfstein Advances in Cell Culture Process Development: Tools and Techniques for Improving Cell Line Development and Process Optimization: Biotechnology Progress, 24: 727-734 (2008). http://www3.interscience.wiley.com/journal/121398262/abstract

Z. Jiang and S.T. Sharfstein, Sodium Butyrate Stimulates mAb Over-expression in CHO Cells by Improving Gene Accessibility, Biotechnology and Bioengineering, 100: 189-194 (2008). http://www3.interscience.wiley.com/journal/117346235/abstract

A. Venkiteshwaran, P. Heider, S. Matosevic, A. Bogsnes, A. Staby, S. Sharfstein, and G. Belfort  Optimized removal of soluble host cell proteins for the recovery of met-human growth hormone inclusion bodies from Escherichia Coli cell lysate using crossflow microfiltration, Biotechnology Progress, 23: 667-672. (2007). http://www3.interscience.wiley.com/journal/121398909/abstract

J.H. Nam M. Ermonval, and S.T. Sharfstein, Cell attachment to microcarriers affects growth, metabolic activity, and culture productivity in bioreactor culture,  Biotechnology Progress, 23: 652 -660 (2007). http://www3.interscience.wiley.com/journal/121398951/abstract

D. Shen and S.T. Sharfstein, Genome-Wide Analysis of the Transcriptional Response of Murine Hybridomas to Osmotic Shock, Biotechnology and Bioengineering, 93: 132-145 (2006). http://www3.interscience.wiley.com/journal/112098359/abstract

Z. Jiang, Y. Huang, and S.T. Sharfstein, Regulation of Recombinant Monoclonal Antibody Production in Chinese Hamster Ovary Cells: A Comparative Study of Gene Copy Number, mRNA Level and Protein Expression, Biotechnology Progress, 22: 313-318 (2006). One of the 10 most accessed articles of 2006 and 20 most cited papers in 2006-2007 from Biotechnology Progress. http://www3.interscience.wiley.com/journal/121410373/abstract

K.M. McNeeley, Z. Sun, and S.T. Sharfstein, Techniques for Dual Staining of DNA and Intracellular Immunoglobulins in Murine Hybridoma Cells: Applications to Cell-Cycle Analysis of Hyperosmotic Cultures, Cytotechnology, 48: 15-26 (2005). http://www.springerlink.com/content/74u2447k61ux850n/fulltext.pdf

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). http://www3.interscience.wiley.com/journal/121400780/abstract

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, 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).

Gambhir, S.S., Barrio, J.R., Wu, L., Iyer, M., Namavari, M., Satyamurthy, N., Parrish, C., MacLaren, D.C., Borghei, A.R., Bauer, E., Green, L.A., Sharfstein, S., Berk, A.J., Cherry, S.R., Phelps, M.E., and Herschman, H.R.  Imaging of adenoviral directed herpes simplex virus Type 1 thymidine kinase reporter gene expression in mice with ganciclovir.  J. Nucl. Med. 39:2003-2011 (1998). (Awarded 3^rd place for Outstanding Basic Science Investigations for 1998)

L.A. Green, S.S. Gambhir, A. Srinivasan, P.K. Banerjee, C.K. Hoh, S.R. Cherry, S. Sharfstein, J. Bario, H. Herschman, and M.E. Phelps, Non-Invasive Methods for Quantitating Blood Time-Activity Curves from Mouse PET Images Obtained with Fluorine-18-Flurodeoxyglucose, J. Nuclear Medicine, 39:729-734 (1998).

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, 57:172-186 (1998).

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: 434-437 (1996).

S.T. Sharfstein and J.D. Keasling, Polyphosphate Metabolism in Escherichia coli, Annals New York Academy of Science, 745:77-91 (1994).

A. Mancuso, S.T. Sharfstein, S.N. Tucker, D.S. Clark, and H.W. Blanch, Examination of Primary Metabolic Pathways in a Murine Hybridoma with Carbon-13 Nuclear Magnetic Resonance Spectroscopy, Biotechnology and Bioengineering, 44:563-585 (1994).

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, 43:1059-1074 (1994).

S.T. Sharfstein, B. Gaillard, H.W. Blanch, and D.S. Clark, Functional Differentiation and Primary Metabolism of Mouse Mammary Epithelial Cells in Extended Batch and Hollow Fiber Culture, Biotechnology and Bioengineering, 40:672-680 (1992).

G. Agopian, P. James, S. Knee, and S. Sharfstein, Novel Technique for Determining Magnet Cleanliness - NMR Spectroscopy, IEEE Transactions on Magnetics, 23:3602 - 3604 (1987).

Invited Book Chapters

Stephanie Curley, Sarah Nicoletti, and Susan T. Sharfstein, “Applications of Nanotechnology to Bioprocessing” Comprehensive Biotechnology, 3rd Edition, Elsevier (2019), submitted

Payel Datta, Robert J. Linhardt, and Susan T. Sharfstein, “Industrial Production of Glycosaminoglycans” in Reference Module in Life Sciences, Elsevier (2017) ISBN 9780128096338, https://doi.org/10.1016/B978-0-12-809633-8.12224-1.

Hussain Dahodwala and Susan T. Sharfstein, “The ‘Omics revolution in CHO biology: Roadmap to improved CHO productivity”, in Heterologous Protein Production in CHO Cells, P. Meleady, ed. Methods in Molecular Biology, Humana Press v1603, p153-168 (2017).

N. Cady, T.J. Begley, M. Bergkvist, S.T. Sharfstein, A.E. Kaloyeros. Nanobiological Sensor Technologies - revised. in Dekker Encyclopedia of Nanoscience & Nanotechnology. CRC Press (2013).

Susan T. Sharfstein and Sarah Nicoletti, “Applications of Nanotechnology to Bioprocessing” in The Nanobiotechnology Handbook, Yubing Xie, ed. Taylor and Francis Group, p323-368 (2013) 

Mikael R. Andersen, *Jong Hyun Nam, and Susan T. Sharfstein, “Protein Glycosylation: Analysis, Characterization, and Engineering” in The Encyclopedia of Industrial Biotechnology, Bioprocess, Bioseparation, and Cell Technology, Michael Flickinger, ed. John Wiley & Sons, Inc., p1-49. (2011) Published Online: 16 MAY 2011 DOI: 10.1002/9780470054581.eib649.

Susan T. Sharfstein and Christian Kaisermayer, "Microcarrier culture" in The Encyclopedia of Industrial Biotechnology, Bioprocess, Bioseparation, and Cell Technology, Michael Flickinger, ed. John Wiley & Sons, Inc., p 3450-3468 (2010).

Susan T. Sharfstein, Duan Shen, Thomas R. Kiehl and Rui Zhou, "Molecular Response to Osmotic Shock" in Cellular Engineering v.5: Systems Biology, M. Al-Rubeai and M. Fussenegger, ed. Springer NL p213-236 (2007).

Susan T. Sharfstein and Jong Hyun Nam, "Protein Glycosylation: Analysis and Characterization" in Bioseparation and Bioprocessing, 2^nd ed., G. Subramanian, ed. Wiley-VCH p631-662 (2007).

Peer-reviewed Conference Proceedings  

S. Sharfstein, B. Barquera, M. Hanna, Biotechnology and Bioprocessing and Microbiology Laboratory Courses: A Model for Shared Used of Instructional Laboratories between Engineering and Science, Proceedings of 2008 American Society for Engineering Education Annual Conference and Exposition (2008). http://soa.asee.org/paper/conference/paper-view.cfm?id=7430

A.B. Samuels, S. Sharfstein, and L.L. Martin, Optimization of mAb Synthesis via the Application of an IDEAS Formulation, Proceedings of the 2004 AIAA/ISSMO Multidisciplinary Analysis and Optimization Conference (2004).

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). http://soa.asee.org/paper/conference/paper-view.cfm?id=15569

Honors and Awards

2017-18 Fulbright Global Scholar Award

2015- Biotechnology Subject Editor, Elsevier Life Science Reference Module

2015-16 SUNY Research Foundation Faculty Fellow