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Abstract

 

Upon intravascular hemolysis (i.e. red blood cell lysis), cell-free hemoglobin (Hb) is released into the systemic circulation, which may subsequently release its iron-containing ligand – heme. Both cell-free Hb and heme are highly reactive and toxic species, that elicit vasoconstriction, systemic hypertension, and oxidative tissue injury. Under normal physiological conditions, specialized plasma proteins haptoglobin (Hp) and hemopexin (Hpx) scavenge and neutralize cell-free Hb and heme, respectively. Unfortunately, acute or chronic hemolytic conditions overwhelm these natural scavenger systems, leading to harmful sequalae such as acute kidney injury and end-organ damage. In this talk, I will give an overview of techniques my lab has developed to manufacture apohemoglobin (apoHb), an analogue of Hpx generated by removing heme from Hb, and to purify Hp. Our purification strategies rely on simple observations that enable facile production of these proteins using tangential flow filtration, a scalable size-based separation system. I will then demonstrate how we can combine these two proteins – apoHb and Hp – to generate a single protein complex that can dually scavenge cell-free Hb and heme to treat hemolytic conditions.

 

 

Biosketch

 

Professor Palmer is Associate Dean for Research in the College of Engineering, Fenburr Ohio Eminent Scholar in Nanotechnology, and Professor of Chemical and Biomolecular Engineering at The Ohio State University. Palmer’s research interests encompass the development of novel hemoglobin-based oxygen carriers for a variety of applications in transfusion medicine as red blood cell substitutes and tissue engineering as oxygen-carrying perfusates. His lab is also developing scavengers of hemoglobin, heme and iron, non heme-based plasma substitutes, and monocyte/macrophage targeted drug delivery systems. He is author of more than 148 peer reviewed publications. Among others, he received the 2021 Lumley Interdisciplinary Research Award from The Ohio State University College of Engineering, and the 2021 Gaden Award from the journal Biotechnology & Bioengineering (Wiley) in recognition of a "truly outstanding paper". Prof. Palmer currently serves on the International Scientific Advisory Committee on Blood Substitutes, and is a member of the Bioengineering, Technology, and Surgical Sciences Study Section at the National Institutes of Health. He served as department chair from 2014-2019. In 2015, he was inducted into the College of Fellows of the American Institute for Medical and Biological Engineering. Palmer’s research is supported by grants from the National Institutes of Health and the Department of Defense.

  • Leah McCarthy

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