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 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 adult hematopoiesis (hematopoietic stem cell biology). This process results in billions of cells that are produced daily in a highly regulated fashion to provide all functional blood cell types (neutrophils, eosinophils, basophils, monocytes/macrophages, platelets, and erythrocytes) in order to maintain homeostatic cell counts, and other tissue cells (mast cells and osteoclasts). Adult hematopoiesis is located in the bone marrow and is initiated by hematopoietic stem cells (HSC). These 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:

  • Pathogen inactivation of red blood cell and platelet products
  • Evaluation of lyophilized fresh frozen plasma
  •  Evaluation of lyophilized platelet products
  • 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

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:

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

1. Zhang C, D'Alessandro A, Wellendorf AM, Mohmoud F, Serrano-Lopez J, Perentesis J, Komurov K, Alexe G, Stegmaier K, Whitsett J, Grimes HL, Cancelas JA. KLF5 controls glutathione metabolism to suppress p190-BCR-ABL+ B-cell lymphoblastic leukemia. Oncotarget Jul 3, 2018;9(51)29665-79. PMID: 30038712, PMC6049869

2. Mock DM, Nalbant D, Kyosseva SV, Schmidt RL, An G, Matthews NI, Vlaar APJ, van Bruggen R, de Korte D, Strauss RG, Cancelas JA, Franco RS, Veng-Pedersen P, Widness JA. Development, validation, and potential applications of biotinylated red blood cells for posttransfusion kinetics and other physiological studies: evidenced-based analysis and recommendations. Transfusion Aug 2018;58(8):2068-81. Review. PMID 29770455

3. Roy S, Rai P, Eiymo Mwa Mpollo MS, Chang KH, Rizvi T, Shanmukhappa SK, VandenHeuvel K, Aronow B, Inagami T, Cancelas JA, Malik P. Angiotensin receptor signaling in sickle cell anemia has a reno-protective effect on urine concentrating ability but results in sickle glomerulopathy. Am J Hematol Jul 2018;93(7):E177-E181. (Letter) PMID 29675906, NIHMS961332, PMC6037553

4. Fang J, Muto T, Kleppe M, Bolanos LC, Hueneman KM, Walker CS, Sampson L, Wellendorf AM, Chetal K, Choi K, Salomonis N, Choi Y, Zheng Y, Cancelas JA, Levine RL, Starczynowski DT. TRAF6 mediates basal activation of NF-κB necessary for hematopoietic stem cell homeostasis. Cell Rep 2018 Jan 30;22(5):1250-62. PMID 29386112, NIHMS966903, PMC5971064

5. Serrano-Lopez J, Nattamai K, Pease NA, Shephard MS, Wellendorf AM, Sertorio M, Smith EA, Geiger H, Wells SI, Cancelas JA, Privette Vinnedge LM. Loss of DEK induces radioresistance of murine restricted hematopoietic progenitors. Exp Hematol 2018 Mar;59:40-50.e3. PMID 29288703, PMC5844846

6. Lee JM, Govindarajah V, Goddard B, Hinge A, Muench DE, Filippi MD, Aronow B, Cancelas JA, Salomonis N, Grimes HL, Reynaud D. Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation of Gfi1 expression. J Exp Med 2018 Feb 5;215(2):627-44. PMID 29282250, PMC5789409

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 & Cell Biology of Cincinnati Children’s Hospital Medical Center.