Hoxworth

Research

Research at the Hoxworth Blood Center has been carried out since its founding in 1938, by Paul I Hoxworth MD. Tibor Greenwalt, who succeeded him as director, worked to transform blood banking into the field of transfusion medicine, and initiated a dedicated research division in 1979. Jose Cancelas, MD, PhD, the current director, continues to foster this momentum.

The goal of the Research Division is to link basic research with clinical care, leading to improved methods that ensure the quality, safety and efficacy of the blood and hematopoietic cell supply. The research program has multiple components, including clinical research, basic biological research, and translational research.

The division is one of the leaders in the coordination of research projects developed for the advancement of transfusion medicine, including FDA required clinical trials for licensing new transfusion medicine-related products. These projects encompass a broad range of studies. They include the evaluation of new methods for processing and storing red blood cells (RBCs), platelets, and plasma, pathogen inactivation treatment of RBCs and platelets; and also the development and testing of new assays used in these evaluations.

Basic research in the division focuses on the study of blood-forming cells during the process of pluripotent and hematopoietic stem cell derived hematopoiesis. The group attempts to identify and understand the molecular and cellular signals controlling blood formation in vivo and in the dish. They are of clinical interest because of their potential use in stem cell and gene therapy.

Currently, we are developing new methods to study the basic biology and regulation of adult stem cell proliferation and differentiation. Our aim is to link these studies with bioengineering processes that might allow us to develop blood cell products from stem cells. There are two major areas of focus in our laboratories:

Current Projects:

  • Development of alternative platelet storage systems
  • Pathogen inactivation of red blood cell and platelet products
  • Evaluation of lyophilized plasma and platelet products
  • Polarity and Rho GTPase activity in stem cells and leukemic stem cells
  • Targeting small GTPases and their signaling pathways in acute lymphoblastic leukemia
  • Non cell-autonomous signaling controlling hematopoietic stem cell self-renewal

Contracted Research

Expertise:

  1. Radioisotope labeling methods for measurement of red cell recovery and survival using chromium-51 and technetium-99m.
  2. Radioisotope labeling methods for measurement of platelet recovery and survival using chromium-51 and indium-111.
  3. Morphologic and functional tests of red blood cells including: adenosine 5’ triphosphate (ATP), 2,3 diphosphoglycerate (DPG), supernatant hemoglobin, hemolysis, osmotic fragility, blood gases, glucose, sodium, potassium, lactate, morphology, rejuvenation of ATP and 2,3 DPG and flow-cytometry measurement of microparticles (microvesicles), and phosphatidylserine/phosphatidylethanolamine exposure.
  4. Evaluation of leukoreduced products including flow-cytometric, low event leukocyte counting and percent cell loss, as well as residual proliferating T cell populations.
  5. Morphologic and functional platelet test including: hypotonic shock response, extent of shape change, ATP, morphology, aggregation, lactate dehydrogenase and flow-cytometry measurement of CD62-P (P-selectin), phosphatidylserine exposure and microparticles and thromboelastography and thrombin generation assays.
  6. Plasma functional and antigenic protein and coagulation assays.
  7. Evaluation of different automated blood collection systems/technologies.
  8. Pathogen reduction studies in blood components.

Compliance:

All studies are reviewed and approved by the Institutional Review Board of the University of Cincinnati Medical Center and Radiation Safety where applicable. Current Good Manufacturing Practices are followed in performance of all procedures, and the laboratory meets the standards of all sponsors as determined by on-site inspections.

Selected Publications:

The Research Divisions findings have been published in prestigious, peer-reviewed, national and international journals. A few examples published in the last 5 years can be found below:

Taniguchi Ishikawa E, Chang KH, Nayak R, Olsson HA, Ficker AM, Dunn SK, Madhu MN, Sengupta A, Whitsett JA, Grimes HL, Cancelas JA Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated β1/β2-integrin trafficking. Nat Commun. 2013;4:1660.

Chang KH, Sengupta A, Nayak RC, Duran A, Lee SJ, Pratt RG, Wellendorf AM, Hill SE, Watkins M, Gonzalez-Nieto D, Aronow BJ, Starczynowski DT, Civitelli R, Diaz-Meco MT, Moscat J, Cancelas JA.p62 is required for stem cell/progenitor retention through inhibition of IKK/NF-κB/Ccl4 signaling at the bone marrow macrophage-osteoblast niche. Cell Rep. 2014 Dec 24;9(6):2084-97.

Chang KH, Nayak RC, Roy S, Perumbeti A, Wellendorf AM, Bezold KY, Pirman M, Hill SE, Starnes J, Loberg A, Zhou X, Inagami T, Zheng Y, Malik P, Cancelas JA. Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem cells/progenitors through endothelial AT₂R and cytoskeletal dysregulation. Nat Commun. 2015 Jan 9;6:5914.

Nayak RC, Trump LR, Aronow BJ, Myers K, Mehta P, Kalfa T, Wellendorf AM, Valencia CA, Paddison PJ, Horwitz MS, Grimes HL, Lutzko C, Cancelas JA. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells. J Clin Invest. 2015 Aug 3;125(8):3103-16

Worsham DN, Reems JA, Szczepiorkowski ZM, McKenna DH, Leemhuis T, Mathew AJ, Cancelas JA; Biomedical Excellence for Safer Transfusion (BEST) Collaborative Group.

Cancelas JA, Slichter SJ, Rugg N, Pratt PG, Nestheide S, Corson J, Pellham E, Huntington M, Goodrich RP. Red blood cells derived from whole blood treated with riboflavin and ultraviolet light maintain adequate survival in vivo after 21 days of storage. Transfusion 2017 May;57(5):1218-25.

Cancelas JA, Gottschall JL, Rugg N, Graminske S, Schott MA, North A, Huang N, Mufti N, Rico S, Corash L. Red blood cell concentrates treated with the amustaline (S-303) pathogen reduction system and stored for 35 days retain post-transfusion viability: results of a two-centre study. Vox Sang 2017 Apr;112(3)210-8.

Cancelas JA, Scott EP, Bill JR. Continuous CD34+ cell collection by a new device is safe and more efficient than by a standard collection procedure: results of a two-center, crossover, randomized trial. Transfusion 2016 Nov;56(11):2824-32.

Cancelas JA, Padmanabhan A, Le T, Ambruso DR, Rugg N, Worsham DN, Pinkard SL, Graminske S, Buck J, Goldberg J, Bill J. Spectra Optia granulocyte apheresis collections result in higher collection efficiency of viable, functional neutrophils in a randomized, crossover, multicenter trial. Transfusion, 2015 Apr;55(4):748-55.

For more information please contact Neeta Rugg (Assistant Director, Research) at (513) 558-1525.