Biochemical and Biomedical Engineering, Bioreactor, Bioprocess, Fed-batch, Perfusion, Hollow Fibre, Hybridoma, CHO, Hematopoietic Cells
Professor
Office:
MSL 207
Education
Massachusetts Institute of Technology, 1989, Sc.D.
Massachusetts Institute of Technology, 1986, S.M.
Harvard College, 1981, A.B.
Research Interests

Many recent developments in biological and medical research have greatly expanded the prospects for regenerative medicine. Cell-based therapies have the potential to provide improved treatments for major diseases such as cancer and diabetes. In collaboration with stem cell researchers (Drs. Eaves, Kieffer and Humphries), we are investigating how to more efficiently optimize therapeutic cell bioprocesses. This includes optimizing the complex cytokine effects on stem cell self-renewal or progenitor differentiation, as well as developing novel analytical technologies (Drs. Hansen and Turner).
Mammalian cells are widely used for the production of therapeutic proteins in the biotechnology industry. We are investigating cellular physiology and engineering approaches in order to better understand and accelerate the development of biotechnology production processes. To improve the design and operation of cell culture devices, we perform experimental and mathematical investigations of their hydrodynamic and transport phenomena. The research topics range from engineering cells to bioreactor engineering.
Our multi-disciplinary, collaborative research projects and the many advantages of the Vancouver location provide an exceptional research environment. Our lab welcomes highly motivated applicants with demonstrated ability for high-performance graduate or postdoctoral research.

Publications
  • Konorov S.O., Schulze H.G., Gage B.K., Kieffer T.J., Piret J.M., Blades M.W., Turner R.F., “The Process Analytical Utility of Raman Microspectroscopy in the Directed Differentiation of Human Pancreatic Insulin-positive Cells”, Anal Chem., 87:10762-9, 2015.
  • Sikorski D., Caron N.J., VanInsberghe M., Zahn H., Eaves C.J., Piret J.M., Hansen C.L., “Clonal Analysis of Individual Human Embryonic Stem Cell Differentiation Patterns in Microfluidic Cultures” J. Biotechnol., 10:1546-1554 2015.
  • Bubela T., McCabe C., Archibald P., Atkins H., Bradshaw S.E., Kefalas P., Mujoomdar M., Packer C., Piret J., Raxworthy M., Soares M., Viswanathan S., “Bringing Regenerative Medicines to the Clinic: The Future for Regulation and Reimbursement”, Regen. Med.10:897–911, 2015.
  • Baylis, J.R., Yeon, J.H., Thomson, M.H., Kazerooni, A., Wang, X., St John, A.E., Lim, E.B., Chien, D. Lee. A, Zhang, J.Q., Piret, J.M., Machan, L.S., Burke, T.F., White, N.J., and Kastrup, C.J. “Self-fueled Particles that Transport Cargo Through Flowing Blood and Halt Hemorrhage” Science Advances,1:e1500379, 2015.
  • Chan M.T., Lim G.E., Yang Y.H.C., Alejandro E.U., Hoesli C., Piret J.M., Warnock G.L. and Johnson J.D., “Effects of insulin on human pancreatic cancer progression modeled in vitro” BMC Cancer, 14:814-826, 2014.
  • Nasseri S.S., Ghaffari N., Braasch K., Jardon M.A., Butler M., Kennard M., Gopaluni B., Piret J.M., “Increased CHO Cell Fed-Batch Monoclonal Antibody Production using the Autophagy Inhibitor 3-MA or Gradually Increasing Osmolality”, Biochemical Eng. J., 91:37–45, 2014.
  • Bruin J.E., Erener S., Vela J., Hu X., Johnson J.D., Kurata H.T., Lynn F.C., Piret J.M., Asadi A., Rezania A., Kieffer T., “Characterization of polyhormonal insulin-producing cells derived in vitro from human embryonic stem cells”, Stem Cell Research, 12:194-208, 2014.
  • Konorov, S. Schulze, G.H., Piret, J., Blades, M., Turner, R., “Label-free determination of the cell cycle phase in human embryonic stem cells by Raman microspectroscopy”, Anal. Chem., 85:8996-9002, 2013.
  • Caron N.J., Gage B.K., O’Connor M.D., Eaves C.J., Kieffer T.J., Piret J.M., “A Human Embryonic Stem Cell Line Adapted for High Throughput Screening”, Biotechnol. Bioeng., 110:2706–2716, 2013.
  • Schulze G.H., Konorov S., Piret, J., Blades, M., Turner, R., “Label-free imaging of mammalian cell nucleoli by Raman microspectroscopy”, Analyst, 138:3416–3423, 2013.
  • Sloma, I., Imren, S., Beer, P.A., Zhao, Y., Lecault, V., Leung, D., Raghuram, K., Brimacombe, C., Lambie, K., Piret, J., Hansen, C., Humphries, R.K., Eaves, C.J., “Ex Vivo Expansion of Normal and Chronic Myeloid Leukemic Stem Cells without Functional Alteration Using a NUP98HOXA10 Homeodomain Fusion Gene”, Leukemia, 27:159-169, 2013.
  • Kim D.Y., Chaudhry M.A., Kennard M.L., Jardon M.A., Braasch K., Butler M., Piret J.M., “Fed-Batch CHO Cell t-PA Production and Feed Glutamine Replacement to Reduce Ammonia Production”, Biotechnol. Prog., 29: 165–175, 2013.
  • Tan, Y., Konorov, S. O., Schulze, H. G., Piret J.M., Blades, M.W., Turner, R.F., “Comparative Study Using Raman Microspectroscopy Reveals Spectral Signatures of Human Induced Pluripotent Cells More Closely Resemble those from Human Embryonic Stem Cells than those from Differentiated Cells”, Analyst 137:4509-4515, 2012.
  • Hoesli C.A., Kiang R., Speck M., Mocinecová D., Donald C., Lacík I., Kieffer T.J., Piret J.M. “Reversal of diabetes by allogeneic insulin-producing cells encapsulated in alginate beads generated by emulsion and internal gelation”, Journal of Biomedical Materials Research: Part B – Applied Biomaterials, 100B:1017–1028, 2012.
  • Jardon M.A., Sattha B., Braasch K., Leung A.O., Côté H.C.F., Butler M., Gorski S.M., Piret J.M., “Inhibition of Glutamine-Dependent Autophagy Increases t-PA Production in CHO Cell Fed-batch Processes”, Biotechnol. Bioeng., 109:1228–1238, 2012.
  • Konorov S., Jardon, M.A., Piret, J.M., Blades, M., Turner, R., “Raman microspectroscopy of live cells under autophagy-inducing conditions”, Analyst, 137(20):4662-4668, 2012
  • Schulze G.H., Konorov S., Okuda, K., Piret, J., Blades, M., Turner, R., “A volume-exclusion normalization procedure for quantitative Raman confocal microspectroscopy of immersed samples applied to human embryonic stem cells”, Applied Spectroscopy, 43:360–369, 2012.
  • Hoesli C.A., Johnson J.D., Piret J.M., “Purified Human Pancreatic Duct Cell Culture Conditions Defined by Serum-Free High-Content Growth Factor Screening”, PLoS ONE, 7(3): e33999, 2012.
  • Lecault, V., VanInsberghe, M., Sekulovic S., Mclaughlin, T., Jarandehei, A., Miller, M., Taghipour, F., Falconnet, D., White, A.K., Kent, D.G., Copley, M.R., Eaves, C.J., Humphries, R.K., Piret, J.M, Hansen, C.L. “High-Throughput Analysis of Single Hematopoietic Stem Cell Proliferation in Perfusion Microfluidic Cell Culture Arrays”. Nature Methods 8 :581-586. (2011)
  • White A.K., VanInsberghe M., Petriv O.I., Hamidi M., Sikorski D., Marra M.A., Piret J.M., Aparicio S., Hansen C.L., “High-throughput microfluidic single-cell RT-qPCR”, PNAS,108:1399-4004, 2011.
  • Sekulovic S., Gasparetto M., Lecault V., Hoesli C.A., Kent D.G., Rosten P., Wan A., Brookes C., Hansen C.L., Piret J.M., Smith C., Eaves C.J., and Humphries R.K., “Ontogeny stage-independent and high-level clonal expansion in-vitro of mouse hematopoietic stem cells stimulated by an engineered NUP98-HOX fusion transcription factor”, Blood, 118:4366-4376, 2011.
  • Konorov, S.O., Schulze, G.H., Piret, J.M., Blades, M.W., and Turner, R.F.B. “Evidence of marked glycogen variations in the characteristic Raman signatures of human embryonic stem cells”, J. Raman Spectroscopy, 42, 1135–1141, 2011.
  • Konorov, S. Schulze, G.H., Piret, J., Aparicio, S., Turner, R., Blades, M., “Raman microscopy of human embryonic stem cells exposed to heat and cold stress”, Applied Spectroscopy, 65:1380–1386, 2011.
  • Goudar, C.T., Piret J.M. and Konstantinov B. “Estimating Cell Specific Oxygen Uptake and Carbon dioxide Production Rates for Mammalian Cells in Perfusion Culture”, Biotechnol. Prog., 27:1347-1357, 2011.
  • Konorov, S. Schulze, G.H. Atkins, C., Piret, J., Aparicio, S., Turner, R., Blades, M., “Absolute quantification of intracellular glycogen content in human embryonic stem cells with Raman microspectroscopy”, Anal Chem., 83:6254-6258, 2011.
  • Konorov, S. Schulze, G.H., Piret, J., Aparicio, S., Turner, R., Blades, M., “Raman microscopy-based cytochemical investigations of potential niche-forming inhomogeneities present in human embryonic stem cell colonies”, Applied Spectroscopy, 65:1009-1016, 2011.
  • Szabat M., Kalynyak T.B., Lim G.E., Chu K.Y., Yang Y.H., Asadi A., Gage B.K., Ao Z., Warnock G.L., Piret J.M., Kieffer T.J., Johnson J.D., “Musashi expression in beta-cells coordinates insulin expression, apoptosis and proliferation in response to endoplasmic reticulum stress in diabetes”, Cell Death and Disease, 2:e232, 2011.
  • Szabat, M., Pourghaderi, P., Soukhatcheva, G., Verchere, C.B., Warnock, G.L., Piret, J.M., Johnson, J.D. “Kinetics and genomic profiling of adult human and mouse β-cell maturation”. Islets 3 :175-187. (2011)
  • Hoesli, C.A., Raghuram, K., Kiang, R. Mocinecová, D., Hu, X., Johnson, J.D., Lacík, I., Kieffer, T.J. and Piret, J.M. “Pancreatic Cell Immobilization in Alginate Beads Produced by Emulsion and Internal Gelation”. Biotechnol. Bioeng. 108 (2) :424-434. (2011)
  • Konorov, S.O., Schulze, G.H., Caron, N.J., Piret, J.M., Blades, M.W., and Turner, R.F.B. “Raman microspectroscopic evidence that dry-fixing preserves the temporal pattern of nonspecific differentiation in live human embryonic stem cells”. J. Raman Spectroscopy 82 :5020-5027. (2011)
  • Petriv, O.I, Kuchenbauer, F., Delaney, A.D.,Lecault, V., White, A., Kent, D., Marmolejo, L., Heuser, M., Berg, T., Copley,M., Ruschmann, J., Sekulovic, S. , Antignano, F., Kuroda, E., Ho, V., Benz, C.,Halim, T., Giambra, V., Krystal, G., Takei, C.J.F., Weng, A.P., Eaves, C.,Piret, J., Marra, M. A., Humphries, R.K., and Hansen, C.L. “Comprehensive microRNA Expression Profiling of the Hematopoietic Hierarchy”. PNAS 107 :15443-8. (2010)
  • Goudar, C., Heidemann, R., Biener, R., Boisart, C., Piret, J.M., de Graaf, A., Konstantinov, K. “Metabolic Flux Analysis of CHO Cells in Perfusion Culture by Metabolite Balancing and 2D [13C, 1H] COSY NMR Spectroscopy”. Metabol. Eng. 12 :138-149. (2010)
  • Szabat, M., Johnson, J.D., and Piret, J.M. “Reciprocal Modulation of Adult Beta Cell Maturity by Activin A and Follistatin”. Diabetologia 53 :1680-1689. (2010)
  • Beauchesne, P., Bruce, K.J., Bowen, B.D. and Piret J.M. “Effect of Cell Lysates on Retroviral Transduction Efficiency of Cells in Suspension Culture”. Biotechnol. Bioeng. 105 :1168-1177. (2010)
  • Tayi, V.S., Bowen, B.D., and Piret, J.M. “Mathematical Model of the Rate-limiting Steps for Retrovirus-Mediated Gene Transfer into Mammalian Cells”. Biotechnol. Bioeng. 105 :195-209. (2010)
  • Schulze, G.H., Konorov, S.O., Caron, N.J., Piret, J.M., Blades, M.W., and Turner, R.F.B. “Assessing Differentiation Status of Human Embryonic Stem Cells Noninvasively Using Raman Microspectroscopy”. Anal. Chem. 82 :5020-5027. (2010)
  • Hill J.A., Szabat M., Hoesli C., Gage B.K., Yang Y.H.C., Williams DE, Riedel M., Luciani D.S., Kalynyak T.B., Tsai K., Ao Z., Andersen R.J., Warnock G.L., Piret J.M., Kieffer T.J. and Johnson J.D. “A multi-parameter, high-content, high-throughput screening platform to identify natural compounds that modulate insulin and pdx1 expression”. PLoSONE 5 (9) :e12958. (2010)
  • Hoesli, C.A., Luu, M. and Piret, J.M. “A Novel Alginate Hollow Fiber Bioreactor Process for Cellular Therapy Applications”. Biotechnol. Prog. 25 :1740-1751. (2009)
  • Szabat, M., Luciani, D.S., Piret, J.M. and Johnson, J.D. “Maturation of Adult beta-Cells Revealed using PDX1/Insulin Dual Reporter Lentivirus”. Endocrinol 150 :1627-1635. (2009)
  • Goudar, C.T., Biener, R., Konstantinov B. and Piret J.M. “Error Propagation from Prime Variables into Specific Rates and Metabolic Fluxes for Mammalian Cells in Perfusion Culture”. Biotechnol. Prog. :986-998. (2009)
  • Goudar, C.T., Joeris, K., Konstantinov B. and Piret J.M. “Robust Parameter Estimation during Logistic Modeling of Batch and Fed-batch Culture Kinetics”. Biotechnol. Prog. 25 :801-806. (2009)
  • Chaudhry M.A.S, Bowen B.D., and Piret J.M. “Culture pH and Osmolality Influence Proliferation and Embryoid Body Yields of Murine Embryonic Stem Cells”. Biochem. Eng. J. 45 :126-135. (2009)
  • Chaudhry, M.A.S., Vitalis, T., Bowen, B.D., and Piret, J.M. “Basal Medium Composition and Serum or Serum Replacement Concentration Influences on the Maintenance of Murine Embryonic Stem Cells”. Cytotechnol. 54 :173-179. (2008)
  • Henry, O., Kwok, K.E. and Piret, J.M. “Simpler Non-instrumented Batch and Semi-Continuous Cultures Provide Mammalian Cell Kinetic Data Comparable to Continuous and Perfusion Cultures”. Biotechnol. Prog. 24 :921-931. (2008)
  • Konorov, S.O., Glover C.H., Piret, J.M., Bryan, J., Schulze, H.G., Blades, M.W., Turner, R.F.B. “In Situ Coherent Anti-Stokes Raman Microscopy of Living Embryonic Stem Cells”. Analytical Chemistry 79 :7221-7225. (2007)
  • Drouin, H., Ritter, J.B., Gorenflo, G.M., Bowen, B.D. and Piret J.M. “Cell Separator Operation within Temperature Ranges to Minimize Effects on Chinese Hamster Ovary Cell Perfusion Culture”. Biotechnol. Prog. 23 :1473-1484. (2007)
  • Lu, M., Glover, C.H., Humphries, R.K., Piret, J.M. and Helgason, C.D. “Involvement of tyrosine kinase signaling in maintaining murine embryonic stem cell functionality”. Experimental Hematology 35 :1293-302. (2007)
  • Takuma, S., Hirashima, C., Piret, J. M. “Dependence of CHO Cell Physiology and IgG Production on Glucose Limitation and Increased CO2 Concentrations”. Biotechnol. Bioeng. 97 :1479-1488. (2007)
  • Glover, C.H., Marin, M., Eaves, C.J., Helgason, C.D., Piret, J.M. and Bryan, J. “Meta-analysis of Mouse Embryonic Stem Cell Gene Expression Kinetics Reveals Consistent Early Change of a Small Gene Set under Differentiating Conditions”. PLoS Computational Biology 2 (11) :e158. (2006)
  • Goudar, C.T., Matanguihan, R., Long, E., Cruz, C., Zhang, C., Piret, J.M., and Konstantinov, K.B. “Decreased pCO2 Accumulation by Eliminating Bicarbonate Addition to High Cell-Density Cultures”. Biotechnol. Bioeng. 96 :1107-1117. (2006)
  • Goudar, C.T., Joeris, K., Konstantinov, K.B., Piret, J.M. “Logistic Equations Effectively Model Mammalian Cell Batch and Fed-batch Kinetics by Logically Constraining the Fit”. Biotechnol. Prog. 21 :1109-1118. (2005)
  • Angepat, S., Gorenflo, V.M., Piret, J.M. “Accelerating perfusion process optimization by scanning non-steady-state responses”. Biotechnol. Bioeng. 92 :473-478. (2005)
  • Palmqvist, L., Glover, C.H., Bossen, B., Hsu, L., Lu, M., Piret, J.M., Humphries, R.K. and Helgason, C.D. “Correlation of murine ESC gene expression profiles with functional measures of pluripotency”. Stem Cells 23 :463-480. (2005)
  • Labecki, M., Piret, J.M. and Bowen, B.D. “Effects of Free Convection on Three-Dimensional Protein Transport In Hollow-Fiber Bioreactors”. AIChE Journal 50 :1974-90. (2004)
  • Gorenflo, V.M., Angepat, S., Bowen, B.D., Piret, J.M. “Optimization of an Acoustic Cell Filter with a Novel Air-Backflush System”. Biotechnol. Prog. 19 :30-36. (2003)
  • Audet, J, Miller, C.L., Eaves, C.J., Piret, J.M. “Common and Distinct Features of Cytokine Effects on Hematopoietic Stem and Progenitor Cells Revealed by Dose Response Surface Analysis”. Biotechnol. Bioeng. 80 :393-404. (2002)
  • Audet, J, Miller, C.L., Rose-John, S., Piret, J.M., Eaves, C.J. “Distinct Role of Gp130 Activation in Promoting Self-Renewal Divisions by Mitogenically Stimulated Murine Hematopoietic Stem Cell”. PNAS 98 :1757-1762. (2001)
CHBE 242 Chemical and Biological Process Technology
CHBE 381 Bioprocess Engineering
CHBE 495 Thesis
CHBE 560 Biochemical Engineering
CHBE 566 Topics in Biochemical Engineering
Canadian Society for Chemical Engineers
American Chemical Society
American Institute of Chemical Engineering
International Society for Stem Cell Research