Faculty Profile

Eleftherios T. Papoutsakis

Unidel Eugene du Pont Chair Professor

Joint Professor, Biological Sciences
DBI Faculty Fellow

Education

  • Doctorate – 1980 Purdue University
  • Masters – 1977 Purdue University
  • Bachelors – 1974 National Tech. Univ. of Athens

About The Papoutsakis Group

Papoutsakis serves as the Unidel Eugene DuPoint Chair Professor in the CBE department. He has mentored over 130 graduate students and postdoctoral fellows, including more than 70 PhD students. He was elected to the National Academy of Engineering and is a fellow of all professional societies in his field. He has received numerous professional awards from the American Institute of Chemical Engineers (AIChE, including recently the oldest, most senior William Walker Award), the American Chemical Society (ACS), and the American Society for Microbiology (ASM), the International Metabolic Engineering Society (IMES), the Society for Industrial Microbiology & Biotechnology (SIMB) and the European Society for Animal Cell Technology (ESACT). Papoutsakis’ current research activities are on molecular biotechnology and synthetic biology for sustainable manufacturing and the development of novel human therapeutic modalities. Microbial biotechnologies (Publications 1-4) of solventogenic and acetogenic clostridia for non-phototrophic CO2 fixation with sugar co-utilization (mixotrophy) in syntrophic cocultures and use of microbiomes for waste-plastic valorization. Syntrophic cocultures may lead to unprecedented heterologous cell fusion events to enable supra-physiological efficiencies of carbon and electron utilization thus leading to transformational metabolite yields to green biomanufacturing. Cell and gene therapies (publications 5-10) of the hematopoietic (blood) system with emphasis on the biology of cellular extracellular vesicles (EVs) for targeted cargo delivery to stem cells. EVs are produced by all cells and are an important mode of cis and trans cell-to-cell communication mediated by receptor recognition for targeted EV cargo delivery. This capability is explored to enable novel cell and gene therapy modalities focusing on the crucial blood-making stem cells. EVs play also an important role in cell-culture based biomanufacturing of protein therapeutics. A collaborative project with Prof. Ierapetritou focuses on model-driven optimization of perfusion-bioreactor operations in biomanufacturing. This FDA supported project combines state-of-the art experimental investigations with model building and validation to enable next generation biomanufacturing technologies.

Select Publications

For a complete listing of publications, please view the Full CV.

  1. Charubin, K and Papoutsakis ET. Direct cell-to-cell exchange of matter in a synthetic Clostridium syntrophy enables CO2 fixation, superior metabolite yields, and an expanded metabolic space. Metabolic Engineering. 52: 9-19 (2019).
  2. Charubin, K, Modla, S, Caplan J.L. and Papoutsakis ET. Interspecies microbial cell fusion and large-scale exchange of cytoplasmic proteins and RNA driven by syntrophic dependency. mBio, 11 (5) e02030-20 (2020).
  3. Charubin, K, Streett, HE & Papoutsakis ET. Development of new strong anaerobic fluorescent reporters for Clostridium acetobutylicum and Clostridium ljungdahlii using HaloTag and SNAP-tag proteins. Appl Environ Microbiol 86:e01271-20 (2020).
  4. Otten, JK, Zou, Y, & ET Papoutsakis. The potential of caproate (hexanoate) production using Clostridium kluyveri syntrophic cocultures with Clostridium acetobutylicum or Clostridium saccharolyticum. Front. Bioeng. Biotechnol., 10:965614 (2022).
  5. Jiang J, Kao CY and Papoutsakis ET. How do megakaryocytic microparticles target and deliver cargo to alter the fate of hematopoietic stem cells? J. Controlled Release, 247:1-18 (2017).
  6. Kao CY and Papoutsakis ET. Engineering Human Megakaryocytic Microparticles for Targeted Delivery of Nucleic Acids to Hematopoietic Stem & Progenitor Cells. Science Advances. 4: eaau6762 (2018).
  7. Kao CY & Papoutsakis ET. Extracellular vesicles: exosomes, microparticles, their parts, and their targets to enable their biomanufacturing and clinical applications. Curr. Opin. Biotech., 60: 89-98 (2019).
  8. Escobar, C, Kao CY, Das, S & Papoutsakis ET. 2020. Human megakaryocytic microparticles induce de novo platelet biogenesis in a wild-type murine model. Blood Advances, 4(5): 804-814 (2020).
  9. Das S, Harris JC, Winter EJ, Kao C-Y, Day ES, Papoutsakis ET. 2022. Megakaryocyte membrane-wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells. Bioeng. Transl. Medicine, 8: e10456. doi:10.1002/btm2.10456 (2022).
  10. Belliveau J & ET Papoutsakis. 2022. Extracellular Vesicles Facilitate Large-Scale, Homogenizing Dynamic Exchange of Proteins and RNA Among Cultured Chinese Hamster Ovary (CHO) and Human Cells. Biotechn Bioeng. 119:1222–1238 (2022) (The Journal Cover).

Patents

For a complete listing of patents, please view the Full CV.

  1. Sandstrom, C., Papoutsakis, E.T., Miller, W.M., and Bender, J.G. Flow-through bioreactor with grooves for cell retention, US Patent No. 5,512,480. Issued: 4/30/1996.
  2. Collins, P.C., Papoutsakis, E.T., and Miller, W.M. Method of Determining Progenitor Cell Content of A Hematopoietic Cell Culture. U.S. Patent 6,077,708. Issued: 6/20/2000.
  3. Senger, R.S., Papoutsakis, E.T. Reverse Engineering Genome-Scale Metabolic Network Reconstructions for Organisms With Incomplete Genome Annotation and Developing Constraints Using Proton Flux States and numerically-Determined Sub-Systems”. US patent 8,311,790. Issued: 11/13/2012.
  4. Papoutsakis, ET, Al-Hinai, MA, Jones, SW, Indurthi, DC, Mitchell DK, Fast A. Recombinant clostridia that fix CO2 and CO and uses thereof. US patent 8,759,070. Issued: 6/24/2014.
  5. Papoutsakis ET, Gaida SM. Engineering complex microbial phenotypes with transcription enhancement. US patent 9,023,618 issued: 5/5/2015.
  6. Tracy, B.P., and Papoutsakis, E.T. Methods and compositions for genetically manipulating clostridia and related bacteria with homologous recombination associated proteins. US Patent 9,493,778. Issued: 11/15/2016.
  7. Papoutsakis, E., S. Nicolaou, A. Fast, V. Falara, R. K. Bennett, W. B. Whitaker, J. Gonzalez, M. Antoniewicz. Synthetic methylotrophy to liquid fuels and chemicals. US patent 10,059,920. Issued: 8/28/2018.
  8. Papoutsakis, E, C-Y Kao and J. Jiang Megakaryocytic particles and microparticles for cell therapy and fate modification of stem and progenitor cells. US patent 10,538,738. Issued: 1/21/2020.
  9. Papoutsakis, E., S., W. B. Whitaker, Bennett, R. K. Synthetic methylotrophs. US patent 10,640,746. Issued: 5/20/2020.
  10. Papoutsakis, E., S. Nicolaou, A. Fast, V. Falara, R. K. Bennett, W. B. Whitaker, J. Gonzalez, M. Antoniewicz. Synthetic methylotrophy to liquid fuels and chemicals. US patent 10,717,964 B2. Issued: 7/21/2020.

Awards

For a complete listing of awards, please see Full CV.

  1. National Academy of Engineering, 2018
  2. William Walker Award of the American Institute of Chemical Engineers, AIChE (2022)
  3. Charles Thom Award, Society for Industrial Microbiology & Biotechnology, SIMB (2022)
  4. Fellow, National Academy of Inventors (NAI) (2021)
  5. Fellow of the International Academy of Medical & Biological Engineering (2021)
  6. The 2020 Amer. Soc. for Microbiology (ASM) National Award in Applied Biotechnology
  7. American Chemical Society (ACS), E. V. Murphree Award in Industrial & Engineering Chemistry (2017)
  8. DIC Wang Award for Excellence in Biochemical Engineering, Society for Biological Engineering (SBE) (2013)
  9. James E. Bailey Award for Biological Engineering, (SBE) (2012)
  10. Fellow of the American Chemical Society (ACS) (2011)

Research Areas

  1. Synthetic biology and metabolic engineering of microbial systems for biofuels and chemicals production, with emphasis on synthetic syntrophic microbial consortia for CO2 fixation to enable sustainable manufacturing
  2. Extracellular vesicles and hybrid nano-bioparticles for cell and gene therapies targeting the blood-making (hematopoietic) stem cells
  3. Advanced protein biomanufacturing through perfusion cell culture
Office: 307 BPI
Phone: 302-831-8376
epaps@udel.edu
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