DiplEng, National Technical University of Athens MS, PhD, Purdue University Fellow of The American Academy of Microbiology (AAM) Alpha Chi Sigma Award of the American Institute of Chemical Engineers (AIChE) Founding Fellow, American Institute of Medical & Biological Engineers Additional Awards and Honors Biotechnology of animal and microbial cells; genomics of stem-cell differentiation and clostridial differentiation

Dr. Papoutsakis has moved: he is now a member of the faculty at The University of Delaware in Newark, Delaware.

Research Group Web Site

Biotechnology Training Program

The Papoutsakis Laboratory uses genomic and classical biological and bioengineering tools to understand programs and mechanisms of important genotypes and phenotypes in both mammalian (human in particular) and prokaryotic (bacterial) cells. In mammalian cells, the focus is on the differentiation and lineage commitment of human hematopoietic stem (and progenitor) cells (hHSC) as well as on the activation and differentiation of human T cells, both with Regenerative Medicine (RM) applications in mind (Refs 1-3). HSCs give rise to all cell types in the circulating blood and have been used for several years now for what is widely-known bone-marrow transplantation to support high-dose chemotherapy for hematological malignancies (such as leukemia) but also other malignancies and autoimmune diseases. More recent evidence suggests that hHSC and related cells may transdifferentiate into other cell types, thus generating additional interest in new RM applications. Ex vivo expanded T cells have been used experimentally in cellular immunotherapy applications to treat both viral and malignant diseases. Questions asked include: What culture parameters and transcriptional programs determine commitment of stem cells into the granulocytic (G) or megakaryocytic (Mk) lineage? Is there interlineage plasticity? Can we generate genetic networks or signatures that characterize specific lineage differentiation or important cellular phenotypes such as MK-specific apoptosis or function acquisition by G cells?

In the prokaryotic project, the focus is to develop and use genomic and metabolic engineering tools, both experimental and computational, in order to understand the genomic basis of cellular differentiation (sporulation) and physiology of clostridia (Refs. 4-7). Clostridia are anaerobic, endospore-forming prokaryotes (bacteria) that include strains of importance to human and animal health (the genus includes several important pathogens like Clostridium botulinum, C. tetani, C. perfrigens, and C. difficile) and physiology, cellulose degradation, solvent (butanol, acetone and ethanol) production and bioremediation. In addition to transcriptional analysis by DNA microarrays (Ref. 7), and using Clostridium acetobutylicum as a model organism, we develop new experimental (e.g., ChIP-on-chip, that is, chromatin immunoprecipitation on a “chip” (DNA microarray)) and computational tools that will allow to develop a detailed understanding of the genetic networks (including the determination of the large regulons of important transcription factors) and signal-transduction that underlies the complex phenotypes of sporulation, stress responses, motility, chemotaxis, and germination. Important applied goals include the understanding of the cellular and molecular basis of solvent and carboxylic-acid toxicity, and the generation of tolerant strains for bioprocessing and bioremediation applications. Another goal is the generation of stable, asporogenous solvent overproducing strains for economical solvent production from renewable resources.

References

Paredes, C.J., Alsaker, K.V., and Papoutsakis, E.T., "A comparative genomic view of clostridial differentiation and physiology", Nature Reviews Microbiology, December issue (in press 2005; advance online publication: doi:10.1038/nrmicro1288, October 24, 2005).

Alsaker, K., and Papoutsakis, E.T., "The transcriptional program of early sporulation and stationary phase events in Clostridium acetobutylicum", J. Bacteriol. 187: (2005).

Ramsborg C.G., D. Windgassen, C.J. Paredes and E. T. Papoutsakis, "Molecular insights into the pleiotropic effects of plasma on Ex vivo expanded T-cells using DNA-microarray analysis", Exp. Hematol. 32: 970-990 (2004).

Tummala, S.B., S.G. Junne, and E. T. Papoutsakis. "Antisense RNA downregulation of CoA Transferase combined with alcohol/aldehyde dehydrogenase (AAD) overexpression leads to predominantly alcohologenic Clostridium acetobutylicum fermentations", J. Bacteriol. 185 : 3644-3653 (2003).

Tomas, C., H. Bonarius, K. Alsaker, H. Yang, W. Hendriksen, J. Beamish, C. Paredes and E. T. Papoutsakis "DNA-array based transcriptional analysis of Clostridium acetobutylicum sporulation (SK01) and degenerate (M5) mutants", J. Bacteriol. 185 : 4539-4547 (2003).

Hevehan, D.L., Miller, W.M., and Papoutsakis, E.T., "Differential expression and phosphorylation of distinct STAT3 proteins during granulocytic differentiation", Blood 99: 1627-1637 (2002).

Yang, H., Miller, W.M., and Papoutsakis, E. T., "Higher pH promotes megakaryocytic maturation and apoptosis", Stem Cells 20: 320-328 (2002).

Awards and Honors

• Fellow of The American Academy of Microbiology (AAM)
• Amgen Biochemical Engineering Award, Engineering Conferences International (ECI)
• Merck Cell Culture Engineering (CCE) Award, Engineering Conferences International (ECI)
• Alpha Chi Sigma Award of the American Institute of Chemical Engineers (AIChE)
• Food, Pharmaceutical, and Bioengineering Award, American Institute of Chemical Engineers
• Presidential Young Investigator Award, National Science Foundation
• Founding Fellow, American Institute of Medical & Biological Engineers

Prof. E. Terry Papoutsakis Department of Chemical and Biological Engineering Northwestern University 2145 Sheridan Road Evanston, IL 60208-3120 tel: 847/491-7455 fax: 847/491-3728 E-mail Professor Papoutsakis