The goal of this project is to design and express novel human mutant recombinant hemoglobins (rHbs), which, after reacting with polyethylene glycol (PEG) or other cross-linking reagents, possess appropriate structural and functional properties to serve as hemoglobin-based oxygen carries (HBOCs). The vasoactivity associated with the use of many of the current HBOCs has challenged previous beliefs as to the optimal O2 affinity, cooperatively, Bohr effect, size, viscosity, and other properties needed for HBOCs. rHbs that we have previously prepared and new ones that we will design and express will be used to test both the new paradigms for the design of blood substitutes and the various hypotheses regarding the origin of vasoactivity. Using our Hb expression system in Escherichia coli, we are in a position to design and express any rHbs needed. Our laboratory has extensive experience and is also fully equipped to carry out structural studies using nuclear magnetic resonance (NMR) and functional studies using biochemical-biophysical techniques (e.g., equilibrium oxygen binding, kinetics of ligand binding, etc)on Hbs. A unique feature of this Program Project is the interactions among its component parts. The key investigators of this Program Project have worked together and have published papers together during the past ten years. The scope of this Program Project requires a multidisciplinary approach to the design of novel HBOCs. The structural and biochemical-biophysical results obtained from this project (Project 2) will provide new insights for Projects 1, 3, 4 and 5 as well as the Protein Biochemistry Core. Equally, the results from other components of the Program Project will guide Project 2 in designing the rHbs most effective as HBOCs. We believe that the results obtained from this Program Project will provide new knowledge for the development of safe, reliable HBOCs as blood substitutes.
| Martucci, Alexandre Fabricio; Abreu Martucci, Ana Carolina Carvalho Ferreira; Cabrales, Pedro et al. (2017) Acute kidney function and morphology following topload administration of recombinant hemoglobin solution. Artif Cells Nanomed Biotechnol 45:24-30 |
| Ao-Ieong, Eilleen S Y; Williams, Alexander; Jani, Vivek et al. (2017) Cardiac function during resuscitation from hemorrhagic shock with polymerized bovine hemoglobin-based oxygen therapeutic. Artif Cells Nanomed Biotechnol 45:686-693 |
| Anandan, P; Ortiz, D; Intaglietta, M et al. (2015) Red blood cells flows in rectilinear microfluidic chip. Conf Proc IEEE Eng Med Biol Soc 2015:3225-8 |
| Roche, Camille J; Talwar, Abhinav; Palmer, Andre F et al. (2015) Evaluating the capacity to generate and preserve nitric oxide bioactivity in highly purified earthworm erythrocruorin: a giant polymeric hemoglobin with potential blood substitute properties. J Biol Chem 290:99-117 |
| Cabrales, Pedro; Ortiz, Daniel; Friedman, Joel M (2015) NO supplementation for transfusion medicine and cardiovascular applications. Future Sci OA 1: |
| Krausz, Aimee E; Adler, Brandon L; Cabral, Vitor et al. (2015) Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent. Nanomedicine 11:195-206 |
| Yalcin, Ozlem; Ortiz, Daniel; Williams, Alexander T et al. (2015) Perfusion pressure and blood flow determine microvascular apparent viscosity. Exp Physiol 100:977-87 |
| Yalcin, Ozlem; Ortiz, Daniel; Tsai, Amy G et al. (2014) Microhemodynamic aberrations created by transfusion of stored blood. Transfusion 54:1015-27 |
| Ortiz, Daniel; Briceño, Juan Carlos; Cabrales, Pedro (2014) Microhemodynamic parameters quantification from intravital microscopy videos. Physiol Meas 35:351-67 |
| Palmer, Andre F; Intaglietta, Marcos (2014) Blood substitutes. Annu Rev Biomed Eng 16:77-101 |
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