Williams Laboratory Research Interests
Research in Dr. Williams' laboratory focuses on understanding the biology of the hematopoietic stem cells, including development of gene transfer methods for application in the treatment of severe genetic diseases of the blood system by gene therapy. Currently the laboratory is focusing on analysis of the function of members of the Rho GTPase family, specifically Rac, Cdc42, and Rho in blood cell development and function. Rho GTPases are members of the Ras superfamily and act as molecular switches to control multiple cell processes, such as migration, phagocytosis, cell cycle progression, and apoptosis via activation of multiple kinase pathways. Using gene targeting, transgenic mice, and a variety of specialized bone marrow culture methods, Dr. Williams' laboratory is defining the essential roles of Rho GTPases in blood cell functions, particularly in response to integrin ligation and activation of the receptor tyrosine kinase, c-kit. The laboratory has recently demonstrated that Rac GTPases are key regulators of the engraftment and mobilization functions of hematopoietic stem cells. Much of the basic information derived from these studies is also being applied to improve the methods of gene transfer into hematopoietic stem cells using retrovirus, foamy virus, and lentivirus vectors.
Related Publications
Gu Y, Chae H, Siefring JE, Jasti AC, Hildeman DA, Williams DA: A critical role of RhoH GTPase in T-cell receptor signaling and thymocyte development. Nature Immunology In Press, 2006.
Ghiaur, G, Lee A, Bailey J, Cancelas J, Zheng Y, Williams DA: Inhibition of RhoA GTPase activity enhances hematopoietic stem and progenitor cell proliferation and engraftment In Vivo. Blood, 2006 May 18; [Epub ahead of print]
Schambach A, Bohne J, Chandra S, Will E, Margison G, Williams DA, Baum C: Equal potency of gammaretroviral and lentiviral SIN vectors for expression of O6–methylguanine-DNA-methyltransferase in bone marrow cells. Molecular Therapy, 13(2):391-400, 2006.
Chandra S, Levran O, Jurickova I, Kapur R, Maas C, Henry R, Milton K, Hanenberg H, Auerbach A, Williams DA: A rapid method for retrovirus mediated identification of complementation groups in Fanconi Anemia patients. Molecular Therapy, 12: 976-984, 2005.
Cancelas J, Prabhakar R, Lee A, Zheng Y, Williams, DA: Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nature Medicine, 11 (8) 886-891, 2005
Baum C, Kalle CV, Staal F, Li Z, Fehse B, Schmidt M, Weerkamp F, Karlsson S, Wagemaker G, Williams DA. Chance or necessity? Insertional mutagenesis in gene therapy and its consequences. Molecular Therapy 9: 5-13, 2004.
Murry C, Soonpaa M, Reinecke H, Nakijima H, Nakijimi H, Rubart M, Pasumarthi K, Virag J, Bartelmez S, Poppa V, Bradford G, Dowell J, Williams DA, Field L. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infacts. Nature 428: 664-668, 2004. [Download the Full text or the PDF file]
Baum C and Williams DA: Letter to the Editor. Gene Therapy Needs both Trials and Discussions. Nature 427: 779-781, 2004.
Filippi MD, Harris CE, Meller J, Gu Y, Zheng Y, Williams DA. Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils. Nature Immunology 5: 744-751, 2004. [Download the Full text or the PDF file]
Where possible, article titles are linked to an abstract of the article. Selected citations may also be linked to PDFs of the article available on a Journal's site. Depending on the Journal's publishing policy, you may need a subscription to download the PDF.
For additional information, please contact Dr. Yi Zheng, Division of Experimental Hematology and Cancer Biology, at 513-636-0364. The Division of Experimental Hematology and Cancer Biology can be found in Room 7.205 of Location S (Research Foundation Building).
