Andre Palmer Laboratory for Artificial Blood Research
Top: Dr. Donald Belcher, Quintin O'Boyle, Emily McDonel, Shaun Gu, Chintan Savla, Evan Martindale
Bottom: Ivan Pires, Richard Hickey, Dr. Crystal Bolden-Rush, Dr. Andre Palmer, Savannah Wolfe, Christopher Gilbert, Clayton Cuddington
Group picture taken in 2019
The Palmer lab is focused on the application of chemical engineering fundamentals (i.e. thermodynamics, kinetics/reactor design, and fluid/mass/heat transport) to address key issues in transfusion medicine, tissue engineering and solid organ/limb perfusion. In particular, the research program focuses on two primary areas: 1) engineering novel hemoglobin (Hb)-based oxygen carriers (HBOCs) for various applications in transfusion medicine and 2) engineering HBOCs to improve oxygen transport in tissue engineered constructs as well as solid organs and limbs. During the course of his 23 year academic career, Palmer has designed, synthesized/formulated and characterized the biochemical and biophysical properties of novel HBOCs ranging from tense and relaxed quaternary state polymerized Hbs to solid Hb nanoparticles, and used these materials in diverse applications. More recently, Palmer's lab has leveraged their understanding of the mechanisms underlying acellular Hb/heme/iron-induced oxidative tissue injury toward developing strategies that mitigate oxidative damage towards the entire organism. Towards that goal, Palmer's lab is developing scavengers of hemoglobin, heme and iron, non heme-based plasma substitutes, and monocyte/macrophage targeted drug delivery systems.
National Institutes of Health
1) R01 HL138116
8/9/2017 - 6/30/2023
PEGylated megahemoglobin for use as a red blood cell substitute
2) R01 HL156526
1/15/2021 - 1/14/2025
Engineering a novel biomaterial for oxygen transport applications
3) R01 HL159862
8/01/2021 - 7/31/2025
Bioengineering a Dual Function Protein Construct to Detoxify Heme and Hemoglobin
4) R01 HL158076
12/01/2021 – 11/30/2025
Aerosolized therapy for hemoglobin toxicity in the treatment of hemolytic diseases
5) R01 HL162120
01/01/2022 – 12/31/2025
Bioengineering a novel therapeutic protein complex to minimize the effects of medical device induced hemolysis
Department of Defense
1) W81XWH-18-1-0059 (U.S. Army Medical Research and Materiel Command)
4/15/2018 - 4/14/2023
Next-generation polymerized hemoglobins for use in transfusion medicine
2) W81XWH‐20‐1‐0194 (U.S. Army Medical Research and Development Command)
Berthiaume (PI), Role: co-I
10/1/2020 - 4/30/2023
Hemoglobin, Heme, and Iron Scavenging for Improved Burn Injury Outcomes
Professor Palmer is a global leader in blood substitute research and engineering biomaterials for use in transfusion medicine and tissue engineering. He is currently working to develop safer, more commercially viable red blood cell substitutes that could tide patients over until they receive a blood transfusion.
Among other honors, Dr. Palmer is an Ohio Eminent Scholar and Fellow of The American Institute for Medical and Biological Engineering (AIMBE), which represents the top two percent of researchers in the medical and biological engineering community in the country. In 2021, he received the Gaden award from the Wiley journal Biotechnology and Bioengineering for publishing a high-impact paper reflecting exceptional innovation, creativity, and originality.
He is a member of the NIH BTSS study section and the International Scientific Advisory Committee on Blood Substitutes.
Palmer chaired the William G. Lowrie Department of Chemical & Biomolecular Engineering from 2014-19, and in 2021 was appointed Associate Dean for Research in the College of Engineering. As Associate Dean, he leads the research endeavors of faculty, students and staff, oversees the college’s research operations—totaling more than $160 million in annual research expenditures—and is responsible for growing strategic industry partnerships.
The following technologies are available for licensing.
Universal oxygen (O2) carrying solutions that can replace the O2 storage and transport functions of red blood cells (RBCs) will greatly improve clinical outcomes for trauma victims and patients undergoing high-blood-loss surgical procedures. These O2 carriers are to be used when blood is not readily available, such as on the battlefield, during natural disasters, at the site of a terrorist attack or in rural areas without hospital access. My lab employs a simple approach to design hemoglobin-based O2 carriers (HBOCs) as RBC substitutes. Our design strategy is based on the observation that transfusion of cell-free hemoglobin results in vasoconstriction, systemic hypertension and oxidative tissue injury. The root cause of these side-effects stem from the ability of hemoglobin to extravasate through pores lining the wall of blood vessels, and consequently scavenge nitric oxide from the surrounding vasculature as well as catalyze production of reactive oxygen species. Therefore, our design strategy focuses on increasing the molecular diameter of HBOCs so that these molecules are unable to traverse across the wall of blood vessels into the tissue space to limit/prevent these side-effects. Approaches to accomplish this include: polymerizing hemoglobin into molecular aggregates, conjugating poly(ethylene) glycol/oligosaccharides to the surface of the hemoglobin molecule, encapsulating hemoglobin inside the core of submicron vesicles and using naturally occurring hemoglobin superassemblies from annelids. These simple strategies mitigate the adverse side-effects associated with the infusion of cell-free Hb into the circulatory system.
- A. T. Williams, A. Lucas, C. Muller, C. Munoz, C. Bolden-Rush, A. F. Palmer, P. Cabrales, “Resuscitation from hemorrhagic shock with fresh and stored blood and polymerized hemoglobin,” Shock Feb 21. doi: 10.1097/SHK.0000000000001530. (2020)
- A. T. Williams, C. R. Muller, A. M. Eaker, D. A. Belcher, C. Bolden-Rush, A. F. Palmer, P. Cabrales, “Polymerized hemoglobin with increased molecular size reduces toxicity in healthy guinea pigs,” ACS Applied Bio Materials Apr 14 3, 5:2976–2985. doi: 10.1021/acsabm.0c00039. (2020)
- A. T. Williams, A. Lucas, C. R. Muller, C. Bolden-Rush, A. F. Palmer, P. Cabrales, “Balance between oxygen transport and blood rheology during resuscitation from hemorrhagic shock with polymerized hemoglobin,” Journal of Applied Physiology Jul 1;129(1):97-107. doi: 10.1152/japplphysiol.00016.2020. (2020)
- C. R. Muller, A. Lucas, V. Courelli, A. T. Williams, F. Dos Santos, C. Cuddington, S. Moses, A. F. Palmer, E. Kistler, P. Cabrales, “Resuscitation from hemorrhagic shock after traumatic brain injury with polymerized hemoglobin,” Scientific Reports Jan 28;11(1):2509. doi: 10.1038/s41598-021-81717-3. (2021)
O2 transport remains one of the main limiting factors in culturing large dimension tissue engineered constructs. When mammalian cells are placed in aqueous media, their metabolism and thus growth is severely constrained by the availability of O2. Since O2 is not very soluble in water, my research focuses on approaches to better improve O2 storage and transport to cultured cells, especially cells grown in bioreactors. Towards this goal, we have used HBOCs to deliver increased levels of O2 and physiological O2 gradients to hepatocytes and β-cells housed in hollow fiber bioreactors to serve as a bioartificial liver assist device and bioartificial pancreas, respectively. We have also used HBOCs to deliver O2 to transplanted islets to reduce graft hypoxia and improve graft function.
1. D. Espes, J. Lau, M. Quach, U. Banerjee, A. F. Palmer, P. O. Carlsson, “Co-transplantation of polymerized hemoglobin reduces beta cell hypoxia and improves beta cell function in intramuscular islet grafts,” Transplantation Oct;99(10):2077-82. doi: 10.1097/TP.0000000000000815. (2015)
2. D. A. Belcher, U. Banerjee, C. M. Baehr, K. E. Richardson, P. Cabrales, F. Berthiaume, A. F. Palmer, “Mixtures of tense and relaxed state polymerized human hemoglobin regulate oxygen affinity and tissue construct oxygenation,” PLoS One Oct 11;12(10):e0185988. doi: 10.1371/journal.pone.0185988. (2017)
3. L. Diaz-Starokozheva, D. Das, X. Gu, J. T. Moore, L. R. Lemmerman, I. Valerio, H. M. Powell, N. Higuita-Castro, M. R. Go, A. F. Palmer, D. Gallego-Perez, “Early intervention on ischemic tissue with oxygen nanocarriers enables successful implementation of restorative cell therapies,” Cellular and Molecular Bioengineering May 29;13(5):435-446. doi: 10.1007/s12195-020-00621-4. (2020)
4. D. A. Belcher, A. Lucas, P. Cabrales, A. F. Palmer, “Tumor vascular status controls oxygen delivery facilitated by infused polymerized hemoglobins with varying oxygen affinity,” PLOS Computational Biology Aug 20;16(8):e1008157. doi: 10.1371/journal.pcbi.1008157. (2020)
Plasma substitutes (PSs), although they lack O2 carrying capacity, are an important class of transfusion solution that can maintain blood volume. They are more advantageous compared to RBC transfusion due to the absence of immunological reactions, longer shelf life, cost-effectiveness and reduced risk of infection. However, conventional PSs are often limited by undesirable side effects, such as RBC aggregation and nephrotoxicity (dextrans), coagulation disturbances (hydroxyethyl starches) and limited intravascular retention (albumin). Notwithstanding this minor limitation, albumin is considered a near optimal PS, whose unique molecular size, shape and electrical charge prevents vascular extravasation into most tissues. Despite its natural prevalence in the bloodstream, human serum albumin (HSA) can increase the risk of mortality when administered to patients with increased vascular permeability (i.e., patients suffering from burns, septic shock, ischemia-reperfusion injury and endothelial dysfunction). This occurs in injured vascular endothelium with increased capillary permeability resulting from physical damage, inflammation, neutrophils or endothelial swelling. Our research proposes re-engineering PSs beyond simple blood volume management, by preserving the interaction between the components of blood and the microcirculation, in order to increase perfusion and maximize oxygenation, thus creating a viable alternative to RBC transfusion or to act as a bridge until RBCs are available. We hypothesize that the deleterious effects of HSA extravasation can be decreased/eliminated by polymerizing HSA (PolyHSA), in order to increase its molecular size, prevent extravasation and increase intravascular retention, while simultaneously decreasing its colloid osmotic pressure and increasing its solution viscosity. Our work on PolyHSA has demonstrated its ability to increase plasma viscosity, which induces mechanotransduction of the endothelium and elicits vasodilation and increased tissue perfusion. We have demonstrated that PolyHSA is able to resuscitate animals from hemorrhagic shock, endotoxemia, sepsis, and ischemia reperfusion injury.
1. C. Messmer, O. Yalcin, A. F. Palmer, P. Cabrales, “Small volume resuscitation from hemorrhagic shock with polymerized human serum albumin,” The American Journal of Emergency Medicine Oct;30(8):1336-46. doi: 10.1016/j.ajem.2011.09.018. (2012)
2. C. Castro, D. Ortiz, A. F. Palmer, P. Cabrales, “Hemodynamics and tissue oxygenation after hemodilution with ultrahigh molecular weight polymerized albumin” Minerva Anestesiologica 80: 537-546 (2014)
3. D. A. Belcher, A. T. Williams, A. F. Palmer, P. Cabrales, “Polymerized albumin restores impaired hemodynamics in endotoxemia and polymicrobial sepsis,” Scientific Reports May 25;11(1):10834. doi: 10.1038/s41598-021-90431-z. (2021)
4. D. A. Belcher, A. T. Williams, C. Walser, C. R. Muller, C. J. Munoz, A. F. Palmer, P. Cabrales, “Attenuating ischemia and reperfusion injury with polymerized albumin,” Journal of Applied Physiology Dec 16. doi: 10.1152/japplphysiol.00117.2021. (2021)
Haptoglobin (Hp), hemopexin (Hpx) and transferrin (Tf) are important acute phase proteins, but also exist at relatively high levels (1-8 mg/ml) in normal plasma. With regard to acute and chronic intravascular and extravascular RBC destruction, these proteins play a critical role in the clearance of Hb, heme and iron and facilitate erythropoiesis through processes of iron recycling to the bone marrow and spleen. My lab has developed a hemopexin mimetic (apohemoglobin, apoHb) that can scavenge heme, and when bound to Hp as the apoHb-Hp complex can scavenge and detoxify both heme and cell-free Hb.
- I. S. Pires, D. A. Belcher, R. Hickey, C. Miller, A. K. Badu-Tawiah, J. H. Baek, P. W. Buehler, A. F. Palmer, “Novel manufacturing method for producing apohemoglobin and its biophysical properties,” Biotechnology and Bioengineering Jan;117(1):125-145. doi: 10.1002/bit.27193. (2020)
- I. S. Pires, A. F. Palmer, “Tangential flow filtration of haptoglobin,” Biotechnology Progress Sep;36(5):e3010. doi: 10.1002/btpr.3010. (2020)
- C. J. Munoz, I. S. Pires, J. H. Baek, P. W. Buehler, A. F. Palmer, P. Cabrales, “A novel apo-hemoglobin-haptoglobin complex attenuates the pathobiology of circulating acellular hemoglobin and heme,” American Journal of Physiology Heart and Circulatory Physiology May 1;318(5):H1296-H1307. doi: 10.1152/ajpheart.00136.2020. (2020)
- D. A. Belcher, C. J. Munoz, I. S. Pires, A. T. Williams, P. Cabrales, A. F. Palmer, “Apohemoglobin-haptoglobin complexes attenuate the hypertensive response to low-molecular-weight polymerized hemoglobin,” Blood Advances Jun 23;4(12):2739-2750. doi: 10.1182/bloodadvances.2020002045. (2020)
The Palmer lab strives to support mentored research opportunities for undergraduate students to enrich their academic experience. Each semester the Palmer lab takes 4 to 6 students to work in the lab.
Please include the following documents combined into a single PDF file in the following order.
1. Unofficial OSU transcript
2. One page statement of intent
4. Class schedule for the upcoming semester
Upon completing your application, please email the compiled PDF file to email@example.com . If your application is approved, you will be contacted via email for an additional interview.
Expectations for Working in the Palmer Lab
Prior to working in the lab, you will be required to complete a set of lab standard Ohio State University Environmental Health and Science training modules: https://ehsapps.osu.edu/secure/apps/Training/Training.aspx. After completing this training you will need to complete a series of in lab training sessions including but not limited to chemical safety, biosafety level 2 (BSL2), chemical hygiene plan, and emergency evacuation. Failure to wear personal protective equipment (PPE), to maintain chemical safety, or to perform safe lab practices will result in termination.
When starting work in the lab you will be assigned to work with a graduate student mentor on a selected project. You will also be expected to complete several lab activities including general cleaning/housekeeping, process monitoring, and protein purification. Undergraduate researcher volunteers are expected to work at least 10 hours per week on average. Work hours will need to be performed in 3-hour time slots at a minimum. Lab related communication and data storage must comply with laboratory procedures.
Graduate Research Associates
Donald Belcher, FIrst Place, AIChE Divisional Poster
Ivan Pires, Top 15 U.S. Undergrad Researchers Symposium, North Carolina State
Richard Hickey, NSF Graduate Research Fellowship
The Journal of Controlled Release recently featured the research of Clayton Cuddington from Professor Andre Palmer's group on the cover.
"Injectable biodegradable bi-layered capsule for sustained delivery of bevacizumab in treating wet age-related macular degeneration" was featured in the April 10 2020, Volume 320 issue, pages 442-456.
Announcements and Local News
The Palmer Lab has immediate openings for undergraduate researchers, graduate students, and postdoctoral scholars. Postdoctoral scholars can apply using this web link.
The Andre Palmer Research Laboratory strives to support mentored research opportunities for undergraduate students to enrich their academic experience. Each semester the Andre Palmer Research Laboratory takes 4-6 students to work in the lab. Background in bioengineering, chemical engineering, chemistry, computer science, biochemistry, molecular and cell biology is desired.
Xiangming Gu wins Best Poster at Graduate Research Symposium 2019
Graduate student, Xiangming "Shaun" Gu, presented his research on comprehensive biophysical characterization of polymerized bovine hemoglobin at the Chemical & Biomolecular Engineering Graduate Research Symposium 2019. The poster presentation earned him one of the prizes for Best Poster from over 50 participants.
The Graduate Research Symposium brings together graduate researchers, faculty, and industry representatives annually for a day of research discussion and innovation. More information about the forum can be found here.