EV postdoc: Papoutsakis Lab

University of Delaware Dept. of Chemical & Biomolecular Engineering & the Delaware Biotechnology Institute

Extracellular vesicles for cell and gene therapy applications Extracellular vesicles (EVs) are submicron membrane vesicles that carry RNAs, proteins and lipids from their parent cells during EV generation. Cells use EVs to communicate with other cells by delivering signals through their content, that is, through their RNAs, proteins and/or more complex morphogens. The biology of EVs is now at the forefront of modern cell and molecular biology, yet many issues essential for their applications in cell and gene therapies remain ill understood. Among EVs, the submicron size microparticles (MPs) are the larger ones, while the nanometer-range exosomes are the smaller ones. It is now widely accepted that MPs and exosomes are excellent candidates for enabling safe and potent cell and gene therapies. This project aims to develop novel technologies based on the megakaryocytic MPs (MkMPs), which target and deliver cargo to hematopoietic stem & progenitor cells (HSPCs) with exceptional specificity. The most important feature of these MkMPs is that they specifically target and reprogram HSPCs through an exquisite recognition process. This project is to develop: a) assays for assessing the impact of the MkMP-generation process on the biological effectiveness of the MkMPs; b) cell-culture engineering methods for scalable MkMP production in bioreactors; c) provide a better understanding of the in vivo effect of these MkMPs using an advanced murine system; d) examine MkMPs as a freezable substitute for platelet transfusions; and e) engineering MkMPs for in vivo nucleic-acid delivery to HSPCs. This is a two-year project with the possibility for extension.

References from the Papoutsakis lab: 1. Jiang J, Woulfe, DS and Papoutsakis ET. 2014. Shear enhances thrombopoiesis and production of megakaryocytic (Mk) microparticles that induce Mk differentiation of stem cells. Blood, 124:2094-2103 2. Jiang J, Kao CY and Papoutsakis ET. 2017. How do megakaryocytic microparticles target and deliver cargo to alter the fate of hematopoietic stem cells? J. Controlled Release. 247: 1-18. 3. Kao CY and Papoutsakis ET. 2018. Engineering Human Megakaryocytic Microparticles for Targeted Delivery of Nucleic Acids to Hematopoietic Stem & Progenitor Cells. Science Adv. 4, eaau6762 (2018). 4. Kao CY & Papoutsakis ET. 2019. Extracellular vesicles: exosomes, microparticles, their parts, and their targets to enable their biomanufacturing and clinical applications. Curr. Opin. Biotech. 60: 89-98.

Required qualifications: a recent (last 3 years) PhD in Chemical/Biomolecular Engineering, Bioengineering, Biotechnology or similar. Experience in cell culture, good understanding of cell biology, basic molecular biology and analytical skills, a promising publication record, and strong writing and oral communication skills. Preference will be given to candidates with flowcytometry, and/or cell therapy and/or experience with animal experiments. Applicants with experience in proposal preparation and academic interests are especially sought.

How to apply: Email to E. Terry Papoutsakis (epaps@udel.edu) with a full CV, a 8-10-line career/goals statement, a 2-3 line statement why you are applying for this position, and 3 reference names (name, position, phone, email and relationship to applicant).