Research

Research at the Hoxworth Blood Center has been carried out since its founding in 1938, by Paul I Hoxworth MD. Tibor Greenwalt MD, 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)

• 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

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.

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. A few of the most recent are given below. More may be found under Publications and Patents.

1. Nayak RC, Chang K, Singh AK, Kotlian M, Desai M, Wellendorf AM, Wunderlich M, Bartram J, Mizukawa B, Cuadrado M, Dexheimer P, Barski A, Bustelo XR, Nassar NN, Cancelas JA. Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis. Nat Commun 2022 Jun 1;13(1):3056. doi 10.1038/s41467-022-30651-7. PMID: 35650206 PMC9160250 
2. Ohanian M, Cancelas JA, Davenport R, Pullarkat V, Hervig T, Broome C, Marek K, Kelly M, Gul Z, Rugg N, Nestheide S, Kinne B, Szczepiorkowski Z, Kantarjian H, Pehta J, Biehl R, Yu A, Aung F, Antebi B, Fitzpatrick GM. Freeze-dried platelets are a promising alternative in bleeding thrombocytopenic patients with hematological malignancies. Am J Hematol 2022 Mar 1;97(3):256-266. doi: 10.1002/ajh.26403. Epub 2021 Dec 23. doi: 10.1002/ajh.26403 PMID: 34748664 
3. Hegde S, Gasilina A, Wunderlich M, Lin Y, Buchholzer M, Krumbach OHF, Akbarzadeh M, Ahmadian MR, Seibel W, Zheng Y, Perentesis JP, Mizukawa BE, Vinnedge LP, Cancelas JA, Nassar NN. Inhibition of the RacGEF VAV3 by the small molecule IODVA1 impedes RAC signaling and overcomes resistance to tyrosine kinase inhibition in acute lymphoblastic leukemia. Leukemia. 2022 Mar;36:637-647. Epub 2021 Oct 28. doi: 10.1038/s41375-021-01455-3. Open Access.  PMID: 34711926 PMC8885421  
4. Rubinstein JD, Zhu X, Leemhuis T, Pham G, Ray L, Emberesh S, Jodele S, Thomas S, Cancelas JA, Bollard CM, Hanley PJ, Keller MD, Grimley O, Clark D, Clark T, Lindestam Arlehamn CS, Sette A, Davies SM, Nelson AS, Grimley MS, Lutzko C. Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted. Blood Adv. 2021 Sep 14;5(17):3309-3321. doi: 10.1182/bloodadvances.2021004456. PMID: 34473237 PMC8525242

For more information, please contact:

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

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

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