Research Topics
Genomes and Genes
| David A WilliamsSummaryAffiliation: Cincinnati Children's Hospital Medical Center Country: USA Publications
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Publications
The role of chemokine activation of Rac GTPases in hematopoietic stem cell marrow homing, retention, and peripheral mobilizationJose A Cancelas
Division of Experimental Hematology, Cincinnati Children s Research Foundation, Cincinnati, Ohio 45215, USA
Exp Hematol 34:976-85. 2006....
Children are not little adults: just ask their hematopoietic stem cellsDavid A Williams
Division of Experimental Hematology, Cincinnati Children s Research Foundation and Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
J Clin Invest 116:2593-6. 2006..Such agents are currently clinically available, suggesting that this approach could be used to improve stem cell transplantation and engraftment...- Gene therapy in the treatment of Fanconi anemia, a progressive bone marrow failure syndromeDavid A Williams
Fanconi Anemia Comprehensive Care Center, Cincinnati Children s Hospital Medical Center and University of Cincinnati College of Medicine, Division of Experimental Hematology, Department of Pediatrics, Cincinnati, OH 45229, USA
Curr Opin Mol Ther 7:461-6. 2005..However, disease-specific characteristics make application of viral vector technology difficult. Multiple studies are currently underway to develop a gene therapy approach for treating this disease, including phase I trials... - Medicine. Gene therapy--new challenges aheadDavid A Williams
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
Science 302:400-1. 2003..reinforces the need to develop even more specific gene therapy interventions... - An international conversation on Stem Cell Gene Therapy. 4th Stem Cell Conference on Stem Cell Gene Therapy, Thessaloniki, Greece, 13-17 September 2007David A Williams
Fanconi Anemia Comprehensive Care Center, Divisions of Experimental Hematology and Hematology/Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45215, USA
Mol Ther 15:2058-9. 2007 - Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescenceXiaoling Zhang
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
J Cell Sci 120:1572-83. 2007..These results indicate an intimate link between inflammatory reactive oxygen species and DNA-damage-induced premature senescence in HSCs and progenitor cells, which may play an important role in aging and anemia... - Cdc42 critically regulates the balance between myelopoiesis and erythropoiesisLinda Yang
Division of Experimental Hematology, Children s Hospital Medical Center, Cincinnati, OH 45229, USA
Blood 110:3853-61. 2007..Thus, Cdc42 is an essential regulator of the balance between myelopoiesis and erythropoiesis... - Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group AXiaoling Zhang
Division of Experimental Hematology, Cincinnati Children s Research Foundation and Fanconi Anemia Comprehensive Care Center, Cincinnati Children s Hospital Medical Center, OH 45229, USA
Blood 112:1683-6. 2008..These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway... - TNF-alpha induces leukemic clonal evolution ex vivo in Fanconi anemia group C murine stem cellsJune Li
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
J Clin Invest 117:3283-95. 2007..We conclude that TNF-alpha exposure creates an environment in which somatically mutated preleukemic stem cell clones are selected and from which unaltered TNF-alpha-hypersensitive Fancc-/- stem cells are purged... - Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and chemotaxis of hematopoietic progenitor cellsHee Don Chae
Division of Experimental Hematology, Cincinnati Children s Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Blood 111:2597-605. 2008..Together, we have identified an antagonistic role of RhoH in regulation of cortical F-actin assembly and chemotaxis via suppressing Rac1 membrane targeting and activation in primary HPCs... - Rac2-deficient hematopoietic stem cells show defective interaction with the hematopoietic microenvironment and long-term engraftment failureMichael Jansen
Division of Experimental Hematology, Cincinnati Children s Hospital Research Foundation, Cincinnati, OH 45215, USA
Stem Cells 23:335-46. 2005..Taken together, these data suggest that Rac2(-/-) stem/progenitor cells exhibit abnormal interaction with the hematopoietic microenvironment, which leads to defective long-term engraftment... - Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potentialHaiming Xu
Division of Experimental Hematology and Cancer Biology, Cincinnati Children s Research Foundation, Cincinnati, OH 45229, USA
Blood 114:3557-66. 2009..Our study defines p190-B as a critical transducer element of HSC self-renewal activity and long-term engraftment, thus suggesting that p190-B is a target for HSC-based therapies requiring maintenance of engraftment phenotype... - Signaling and cytoskeletal requirements in erythroblast enucleationDiamantis G Konstantinidis
Cancer and Blood Diseases Institute, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
Blood 119:6118-27. 2012.... - Rac GTPases differentially integrate signals regulating hematopoietic stem cell localizationJose A Cancelas
Hoxworth Blood Center, University of Cincinnati Medical Center, 3130 Highland Avenue, Cincinnati, Ohio, 45267, USA
Nat Med 11:886-91. 2005.... - Rac1 and Rac2 GTPases are necessary for early erythropoietic expansion in the bone marrow but not in the spleenTheodosia A Kalfa
Division of Hematology Oncology, Oncology, Cincinnati Children s Research Foundation, Cincinnati Children s Hospital Medical Center, MLC 7015 Cincinnati, OH 45229 3039, USA
Haematologica 95:27-35. 2010..The role of these Rac GTPases in erythropoiesis has not yet been fully elucidated... - Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative diseaseEmily K Thomas
Division of Experimental Hematology, Cincinnati Children s Research Foundation, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
Cancer Cell 12:467-78. 2007..These data demonstrate that Rac is an additional therapeutic target in p210-BCR-ABL-mediated MPD... - Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of fetal liver with definitive hematopoietic progenitor cellsGabriel Ghiaur
Department of Pediatrics, Cincinnati Children s Research Foundation and Cincinnati Children s Hospital Medical Center, and Hoxworth Blood Center, University of Cincinnati College of Medicine, OH, USA
Blood 111:3313-21. 2008..These data suggest that Rac1 plays an important role in HSC/P migration during embryonic development and is essential for the emergence of intraembryonic hematopoiesis... 
Rho GTPases and regulation of hematopoietic stem cell localizationDavid A Williams
Division of Experimental Hematology, Cincinnati Children s Research Foundation, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
Methods Enzymol 439:365-93. 2008..In addition, it reviews abnormalities of Rho GTPases implicated in human immunohematopoietic diseases and in leukemia/lymphoma...- Inhibition of RhoA GTPase activity enhances hematopoietic stem and progenitor cell proliferation and engraftmentGabriel Ghiaur
Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7013, Cincinnati, OH 45229, USA
Blood 108:2087-94. 2006..This mechanism could provide a novel therapeutic target to enhance HSC therapies... - Genetic deletion of Rac1 GTPase reveals its critical role in actin stress fiber formation and focal adhesion complex assemblyFukun Guo
Division of Experimental Hematology, Children s Hospital Research Foundation, University of Cincinnati, Cincinnati, Ohio 45229, USA
J Biol Chem 281:18652-9. 2006.... - Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftmentLei Wang
Division of Experimental Hematology, Children s Hospital Medical Center, University of Cincinnati, OH 45229, USA
Blood 107:98-105. 2006..These results provide evidence that Cdc42 activity is important for erythropoiesis and for multiple HSP functions, including survival, adhesion, and engraftment... - FIP1L1/PDGFRalpha synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndromeYoshiyuki Yamada
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, OH 45229 3039, USA
Blood 112:2500-7. 2008..The increased proliferation and survival correlated with increased SCF-induced Akt activation. In summary, F/P synergistically promotes MC development, activation, and survival in vivo and in vitro in response to SCF... - Rac2 regulates neutrophil chemotaxis, superoxide production, and myeloid colony formation through multiple distinct effector pathwaysDirk Carstanjen
Division of Experimental Hematology, Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
J Immunol 174:4613-20. 2005..These findings suggest that binding to any single effector is not sufficient to rescue the distinct cellular phenotypes of Rac2-/- PMN, implicating multiple, distinct, and potentially parallel effector pathways... - Importance of murine study design for testing toxicity of retroviral vectors in support of phase I trialsElke Will
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
Mol Ther 15:782-91. 2007.... - Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophilsMarie Dominique Filippi
Division of Experimental Hematology, Cincinnati Children s Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
Nat Immunol 5:744-51. 2004..Thus, we have defined specific sequences in Rac that specify subcellular localization and determine the specificity of Rac2 in neutrophil chemotaxis and superoxide generation... - Rapid lentiviral transduction preserves the engraftment potential of Fanca(-/-) hematopoietic stem cellsLars U W Müller
Division of Experimental Hematology, Cincinnati Children s Research Foundation, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
Mol Ther 16:1154-60. 2008..Collectively, these data support the use of rapid lentiviral transduction for gene therapy in FA... - Reciprocal relationship between O6-methylguanine-DNA methyltransferase P140K expression level and chemoprotection of hematopoietic stem cellsMichael D Milsom
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
Cancer Res 68:6171-80. 2008..These studies have direct translational relevance to ongoing clinical gene therapy studies using MGMT(P140K), whereas the novel mechanistic findings are relevant to the basic understanding of DNA repair by MGMT... - RhoH regulates subcellular localization of ZAP-70 and Lck in T cell receptor signalingHee Don Chae
Division of Experimental Hematology, Cincinnati Children s Research Foundation, Cincinnati Children s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
PLoS ONE 5:e13970. 2010..Together, our results suggest that RhoH regulates TCR signaling via recruitment of ZAP-70 and Lck to CD3ζ in the immunological synapse. Thus, we define a new function for a RhoH GTPase as an adaptor molecule in TCR signaling pathway... - Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemiaBenjamin Mizukawa
Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children s Hospital Medical Center, OH 45229, USA
Blood 118:5235-45. 2011..Furthermore, concurrent exposure to NSC23766, a small-molecule inhibitor of Rac activation, increases the apoptotic effect of ABT-737, indicating the Rac/Bcl-2 survival pathway may be targeted synergistically... - RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling and thymocyte developmentYi Gu
Division of Experimental Hematology, Cincinnati Children s Research Foundation and Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
Nat Immunol 7:1182-90. 2006..These findings suggest that RhoH is a critical regulator of thymocyte development and TCR signaling by mediating recruitment and activation of Zap70... - Stem cell collection and gene transfer in Fanconi anemiaPatrick F Kelly
Fanconi Anemia Comprehensive Care Center, Divisions of Experimental Hematology and Hematology Oncology, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
Mol Ther 15:211-9. 2007..Our early experience shows that stem cell collection is well tolerated in FA patients and suggests that collection be considered as early as possible in patients who are potential candidates for future gene transfer trials... - Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeletonTheodosia A Kalfa
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, MLC 7015, Cincinnati, OH 45229, USA
Blood 108:3637-45. 2006..Thus, deficiency of Rac1 and Rac2 GTPases in mice alters actin assembly in RBCs and causes microcytic anemia with reticulocytosis, implicating Rac GTPases as dynamic regulators of the erythrocyte cytoskeleton organization... - Identification and characterization of mutations in FANCL gene: a second case of Fanconi anemia belonging to FA-L complementation groupAbdullah Mahmood Ali
Experimental Hematology and Cancer Biology, Cincinnati Children s Research Foundation, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
Hum Mutat 30:E761-70. 2009..We identified bi-allelic novel mutations in the FANCL gene and functionally characterized them. To the best of our knowledge, this is the second reported case belonging to the FA-L complementation group... - Rho GTPases in hematopoietic stem cell functionsJose A Cancelas
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
Curr Opin Hematol 16:249-54. 2009..Rho GTPases are now known to be crucial in HSCs response to hematopoietic microenvironment cues. This article will review the known HSC functions, which are regulated by Rho GTPases... - RhoH GTPase: a key regulator of hematopoietic cell proliferation and apoptosis?Yi Gu
Division of Experimental Hematology, Cincinnati Children s Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
Cell Cycle 4:201-2. 2005..In addition, RhoH appears to counteract Rac GTPase activities, suggesting a possible mechanism by which RhoH functions as an antagonist of Rac signaling in the regulation of cell growth and actin-based functions in blood lineages... - Live and let die: in vivo selection of gene-modified hematopoietic stem cells via MGMT-mediated chemoprotectionMichael D Milsom
Cincinnati Children s Research Foundation, Cincinnati Children s Hospital Medical Center, Division of Experimental Hematology, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
DNA Repair (Amst) 6:1210-21. 2007.... - A rapid method for retrovirus-mediated identification of complementation groups in Fanconi anemia patientsSaurabh Chandra
Division of Experimental Hematology and Fanconi Anemia Comprehensive Care Center, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
Mol Ther 12:976-84. 2005..This assay has now been established in a standardized fashion for complementation assignments in FA patients and the subsequent directing of rapid mutation analysis in those patients... - Structure-function based design of small molecule inhibitors targeting Rho family GTPasesNicolas Nassar
Division of Experimental Hematology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA
Curr Top Med Chem 6:1109-16. 2006.... - Rac1 GTPase regulates cell genomic stability and senescenceMarcella Debidda
Division of Experimental Hematology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
J Biol Chem 281:38519-28. 2006..Taken together, our results show that Rac1 activity serves as a regulator of cell senescence through modulation of cellular ROS, genomic stability, and p53 activity... - Rational design and applications of a Rac GTPase-specific small molecule inhibitorHuzoor Akbar
Division of Experimental Hematology, Children's Hospital Research Foundation, Cincinnati, OH, USA
Methods Enzymol 406:554-65. 2006..Thus, NSC23766 is a lead small molecule inhibitor of Rac activity and could be useful for studying Rac-mediated cellular functions and for modulating pathological conditions in which Rac-deregulation may play a role... - HOXB4 inhibits cell growth in a dose-dependent manner and sensitizes cells towards extrinsic cuesElke Will
Department of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
Cell Cycle 5:14-22. 2006..Based on these results we propose that HOXB4 affects cell growth in a dose-dependent manner by sensitizing cells towards extrinsic signals... - Rac2, a hematopoiesis-specific Rho GTPase, specifically regulates mast cell protease gene expression in bone marrow-derived mast cellsYi Gu
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
Mol Cell Biol 22:7645-57. 2002.... - Lenti in red: progress in gene therapy for human hemoglobinopathiesChristof von Kalle
Division of Expermental Hematology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
J Clin Invest 114:889-91. 2004..While some safety concerns must be addressed, this study is an important step toward potential clinical trials of gene therapy for hemoglobinopathies... - The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like diseaseYoshiyuki Yamada
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Blood 107:4071-9. 2006..These results suggest that F/P is not sufficient to induce a HES/CEL-like disease but requires a second event associated with IL-5 overexpression... - Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatasesYi Gu
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
Science 302:445-9. 2003..Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function... - Promoting translational research in academic health centers: navigating the "roadmap"Timothy P Cripe
Division of Hematology Oncology, MLC R7015, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
Acad Med 80:1012-8. 2005..The broad success of this program suggests that it might serve as a model for other academic health centers in promoting and conducting translational research... - Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survivalKyung Hee Chang
Division of Experimental Hematology, Cincinnati Children s Research Foundation, Cincinnati Children s Hospital Medical Center, Cincinnati, OH
Blood 120:800-11. 2012..We conclude that Vav3 represents a novel specific molecular leukemic effector for multitarget therapy in p190-BCR-ABL-expressing acute lymphoblastic leukemia... - Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group MThiyam Ramsing Singh
Division of Experimental Hematology and Cancer Biology, Cincinnati Children s Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
Blood 114:174-80. 2009..Because both mutants restored the formation of FANCD2 foci, we conclude that FANCM functions in an FA core complex-dependent and -independent manner... - A new mechanism of leukemia drug resistance?David A Williams
Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, USA
N Engl J Med 357:77-8. 2007 - Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cellsFeng Chun Yang
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
J Clin Invest 112:1851-61. 2003..Thus, these studies identify a novel interaction between Nf1-/- Schwann cells and Nf1+/- mast cells that is likely to be important in neurofibroma formation... - Chemotherapy for myeloid malignancy in children with Fanconi anemiaParinda A Mehta
Fanconi Anemia Comprehensive Care Center, Cincinnati Children s Hospital Medical Center CCHMC, Cincinnati, Ohio 45229, USA
Pediatr Blood Cancer 48:668-72. 2007..In this report we describe the toxicity of a chemotherapy approach for patients with FA and myeloid malignancy to achieve cytoreduction prior to SCT... - Inflammatory reactive oxygen species-mediated hemopoietic suppression in Fancc-deficient miceDaniel P Sejas
Division of Experimental Hematology, Cincinnati Children s Research Foundation and Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
J Immunol 178:5277-87. 2007..Our data implicate a role of inflammation in pathogenesis of FA and BM failure diseases in general... - Genetic evidence for convergence of c-Kit- and alpha4 integrin-mediated signals on class IA PI-3kinase and the Rac pathway in regulating integrin-directed migration in mast cellsBai Lin Tan
Section of Neonatal Perinatal Medicine, Department of Pediatrics, Indiana University School of Medicine, Indianapolis 46202, USA
Blood 101:4725-32. 2003..These genetic and biochemical data demonstrate that both c-Kit and alpha4 integrin signaling are linked to class IA PI-3kinase and Rac pathways and regulate integrin-directed (haptotactic) migration in mast cells... - In vivo selection of human hematopoietic cells in a xenograft model using combined pharmacologic and genetic manipulationsKaren E Pollok
Herman B Wells Center for Pediatric Research, Department of Pediatrics, The Riley Hospital for Children, Indianapolis, IN 46202, USA
Hum Gene Ther 14:1703-14. 2003.... - RAC2 GTPase deficiency and myeloid cell dysfunction in human and mouseYi Gu
Howard Hughes Medical Institute, H.B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, 1044 W. Walnut Street, Indianapolis, IN 46202, USA
J Pediatr Hematol Oncol 24:791-4. 2002..Together, these data demonstrate a critical and unique role for Rac2 in normal neutrophil function and define a new genetic immunodeficiency syndrome in humans... - A rare complex DNA rearrangement in the murine Steel gene results in exon duplication and a lethal phenotypeSaurabh Chandra
Division of Experimental Hematology, Cincinnati Children s Hospital, Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA
Blood 102:3548-55. 2003..The KitlSl-20J mutation is a unique KitlSl allele and represents an unusual mechanism of mutation... - A theoretically optimized method for cord blood stem cell cryopreservationErik J Woods
Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
J Hematother Stem Cell Res 12:341-50. 2003..6, respectively). This study demonstrated that the use of a theoretically determined optimal cryopreservation method is superior to standard methods for maintaining UCB PCBs with multilineage repopulation potential in NOD/SCID mice... - Role of p38 and ERK MAP kinase in proliferation of erythroid progenitors in response to stimulation by soluble and membrane isoforms of stem cell factorReuben Kapur
Section of Neonatal Perinatal Medicine, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Blood 100:1287-93. 2002..These results suggest that different isoforms of SCF may use different biochemical pathways in stimulation of survival and/or proliferation of erythroid cells... - The Rac2 guanosine triphosphatase regulates B lymphocyte antigen receptor responses and chemotaxis and is required for establishment of B-1a and marginal zone B lymphocytesBen A Croker
Division of Cancer and Hematology and Immunology, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia
J Immunol 168:3376-86. 2002..Rac2 is therefore an essential element in regulating B lymphocyte functions and maintaining B lymphocyte populations in vivo... - Progress reported in two studies of clinical gene transfer into the retinaDavid A Williams
Mol Ther 16:1181. 2008 - Comparison of three retroviral vector systems for transduction of nonobese diabetic/severe combined immunodeficiency mice repopulating human CD34+ cord blood cellsCordula Leurs
, , , , Germany
Hum Gene Ther 14:509-19. 2003..These data demonstrate that vectors based on FVs warrant further investigation and development for medical use... - Side effects of retroviral gene transfer into hematopoietic stem cellsChristopher Baum
Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
Blood 101:2099-114. 2003.... - Phenotypic correction of primary Fanconi anemia T cells with retroviral vectors as a diagnostic toolHelmut Hanenberg
Klinik für Pädiatrische Hämatologie und Onkologie, Zentrum fur Kinderheilkunde, Heinrich Heine Universitat, Dusseldorf, Germany
Exp Hematol 30:410-20. 2002..The aim of this study was to develop a rapid laboratory procedure that is capable of subtyping Fanconi anemia (FA) complementation groups FA-A, FA-C, FA-G, and FA-nonACG patients from a small amount of peripheral blood... - Rac2-deficient mice display perturbed T-cell distribution and chemotaxis, but only minor abnormalities in T(H)1 responsesBen A Croker
Divisions of Cancer, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, South Australia
Immunol Cell Biol 80:231-40. 2002..Cytotoxic T-lymphocyte responses to cytomegalovirus and ovalbumin were also normal. Although Rac2 is required for normal T-lymphocyte migration, its role in the generation of T(H)1 responses to infection in vivo is largely redundant... - Hematoprotection and enrichment of transduced cells in vivo after gene transfer of MGMT(P140K) into hematopoietic stem cellsMichael Jansen
Department of Internal Medicine (Cancer Research, West German Cancer Center, University of Essen Medical School, Essen, Germany
Cancer Gene Ther 9:737-46. 2002..Thus, these data demonstrate efficient protection from hematotoxicity and substantial enrichment of transgenic cells following MGMT(P140K) gene transfer and treatment with different O(6)-alkylating drugs... - The TRQQKRP motif located near the C-terminus of Rac2 is essential for Rac2 biologic functions and intracellular localizationWen Tao
Howard Hughes Medical Institute, USA
Blood 100:1679-88. 2002..These data suggest that precise localization of Rac2 protein in intracellular compartments and/or with other proteins/lipids is a prerequisite for its diverse functions... - Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell developmentFukun Guo
Division of Experimental Hematology and Cancer Biology, Children s Hospital Medical Center, OH, USA
Blood 112:1767-75. 2008..Thus, Rac1 and Rac2 have unique roles in CLP production and share a redundant but essential role in later stages of T-cell development by regulating survival and proliferation signals... - Gene therapy advances but struggles to interpret safety data in small animal modelsDavid A Williams
Mol Ther 13:1027-8. 2006 - New AAV serotypes may broaden the therapeutic pipeline to human gene therapyDavid A Williams
Mol Ther 13:1-2. 2006 - Stable differentiation and clonality of murine long-term hematopoiesis after extended reduced-intensity selection for MGMT P140K transgene expressionClaudia R Ball
National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany
Blood 110:1779-87. 2007.... - CXCL9 inhibits eosinophil responses by a CCR3- and Rac2-dependent mechanismPatricia C Fulkerson
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, OH 45229 3039, USA
Blood 106:436-43. 2005..These results establish evidence that distinct chemokines can use CCR3 to induce opposing signals in eosinophils... - Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarctsCharles E Murry
Department of Pathology, Box 357470, Room D 514 HSB, University of Washington, Seattle, Washington 98195, USA
Nature 428:664-8. 2004..These results indicate that haematopoietic stem cells do not readily acquire a cardiac phenotype, and raise a cautionary note for clinical studies of infarct repair... - Chance or necessity? Insertional mutagenesis in gene therapy and its consequencesChristopher Baum
Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
Mol Ther 9:5-13. 2004..Based on these considerations, we propose approaches to risk prediction and prevention... - Methylguanine methyltransferase-mediated in vivo selection and chemoprotection of allogeneic stem cells in a large-animal modelTobias Neff
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA
J Clin Invest 112:1581-8. 2003.... - Critical roles for Rac1 and Rac2 GTPases in B cell development and signalingMarita J Walmsley
Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK
Science 302:459-62. 2003..Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance... - Vector insertion, mutagenesis and transgene toxicityDavid A Williams
Mol Ther 14:457. 2006 - Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signalingXimei Wu
Department of Medicine, Washington University Medical School, St Louis, MO 63110, USA
Cell 133:340-53. 2008.... - Foamy virus vectors come of ageDavid A Williams
Mol Ther 16:635-6. 2008 - Lentiviral vectors pseudotyped with murine ecotropic envelope: increased biosafety and convenience in preclinical researchAxel Schambach
Department of Hematology, Hemostaseology and Oncology, Hannover Medical School, Germany
Exp Hematol 34:588-92. 2006..High efficiency and superior biosafety in combination with convenient handling will certainly boost the potential applicability of this important vector system... - A "vector drain" in US gene therapy development?Michel Sadelain
Mol Ther 16:801-2. 2008
Research Grants
- Chemoresistance and Stem Cell SelectionDavid Williams; Fiscal Year: 2007..The results from these studies will provide powerful insight into the application of virus vectors to genetic diseases and cancer as well as detailed consequences and benefits of protecting hematopoietic stem cells from DNA damage. ..
- Novel Molecular and Cellular Therapies in Fanconi AnemiaDavid Williams; Fiscal Year: 2007..This grant proposal seeks funding to conduct these clinical trials and further develop retrovirus-mediated complementation analysis in a CAP/CLIA environment for use in clinical management of FA patients. ..
- Rac protein in hematopoietic cell survival and functionDavid Williams; Fiscal Year: 2007....