Research

Research at the Hoxworth Blood Center has been carried out since its founding in 1938, by Paul I Hoxworth MD. Tibor Greenwalt, his successor, worked to transform blood banking into the field of transfusion medicine and initiated a dedicated research division in 1979 during his time as director of the blood center. Ronald Sacher MD, 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, and pathogen inactivation treatment of RBCs and platelets; and also 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 adult hematopoiesis (hematopoietic stem cell biology). This process results in billions of cells that are produced daily in a highly regulated fashion to maintain homeostatic cell counts in circulation and provide all functional blood cell types (neutrophils, eosinophils, basophils, monocytes/macrophages, platelets, and erythrocytes) and other tissue cells (mast cells and osteoclasts). Adult hematopoiesis is located in the bone marrow and is initiated by hematopoietic stem cells (HSC). Which are able to self-renew and differentiate into all types of blood cells. 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 products from adult stem cells. There are two major areas of focus in our laboratories:

  1. Clinical Research in Transfusion Medicine     

  2. Stem Cell Biology  (hematopoietic and mesenchymal/stromal)

Current Projects include:

·      Pathogen inactivation of red blood cell and platelet products

·      Evaluation of RBCs stored in AS-7 (SOLX additive solution FDA-licensed for 8-week storage of RBCs)

·      Validation of a biotin labeling technique for assaying RBC survival 

·      Rac GTPases inhibition in chronic myelogenous leukemia

·      Vav / Rac as a molecular target in pediatric acute lymphoblastic   leukemia

·      Connexin-43 in bone marrow failure after cancer-related chemotherapy

Representative Publications:

The Research Divisions findings have been published in prestigious, peer-reviewed, national and international journals including Nature, Nature Medicine, Cell Stem Cell, Cancer Cell, Proc. Natl. Acad. Sci. USA, Blood, Leukemia and Transfusion.

1. 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 membrane β1/β2-integrin expression. Nat Commun 2013 Apr 3;4:art. No. 1660. doi: 10.1038/ncomms2645. PMID: 23552075, PMCID: 3627399.

2.  Dumont LJ*, Cancelas JA*, Graminske S, Friedman KD, Vassallo RR, Whitley PH, Rugg N, Dumont DF, Herschel L, Siegal AH, Szczepiorkowski ZM, Fender L, Razatos A. In vitro and in vivo quality of leukocyte-reduced apheresis platelets stored in a new platelet additive solution. Transfusion 2013, May;53(5):972-80. PMID: 22882530

3.  Chang KH, Sanchez-Aguilera A, Shen S, Sengupta A, Madhu MN, Ficker AM, Dunn SK, Kuenzi AM, Anrett JL, Santho RA, Agirre X, Perentesis JP, Deininger MW, Zheng Y, Bustelo XR, Williams DA, Cancelas JA. Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation and survival. Blood 2012 Jul 26;120(4):800-11. PMID: 22692505 PMCID: 3412345

4.  Cancelas JA, Dumont LJ, Rugg N, Szczepiorkowski ZM, Herschel L, Siegel A, Pratt PG, Worsham DN, Erickson A, Propst M, North A, Sherman CD, Mufti NA, Reed WF, Corash L. Stored red blood cell viability is maintained after treatment with a second generation S-303 pathogen inactivation process. Transfusion 2011 Nov;51(11):2367-76. PMID 21569044.

(*equal contributing authors)

For more information, please contact:

Clinical studies: Neeta Rugg at (513) 558-1525.

Basic research: Jose Cancelas at (513) 558-1324

For additional information about related research projects, select the following links.

Division of Experimental Hematology of Cincinnati Children’s Hospital Medical Center.