David A Williams

Summary

Affiliation: Cincinnati Children's Hospital Medical Center
Country: USA

Publications

  1. ncbi request reprint The role of chemokine activation of Rac GTPases in hematopoietic stem cell marrow homing, retention, and peripheral mobilization
    Jose A Cancelas
    Division of Experimental Hematology, Cincinnati Children s Research Foundation, Cincinnati, Ohio 45215, USA
    Exp Hematol 34:976-85. 2006
  2. ncbi request reprint Medicine. Gene therapy--new challenges ahead
    David A Williams
    Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Science 302:400-1. 2003
  3. ncbi request reprint An international conversation on Stem Cell Gene Therapy. 4th Stem Cell Conference on Stem Cell Gene Therapy, Thessaloniki, Greece, 13-17 September 2007
    David 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
  4. pmc Children are not little adults: just ask their hematopoietic stem cells
    David 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
  5. ncbi request reprint Gene therapy in the treatment of Fanconi anemia, a progressive bone marrow failure syndrome
    David 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
  6. pmc Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence
    Xiaoling Zhang
    Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Cell Sci 120:1572-83. 2007
  7. pmc Cdc42 critically regulates the balance between myelopoiesis and erythropoiesis
    Linda Yang
    Division of Experimental Hematology, Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Blood 110:3853-61. 2007
  8. pmc Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A
    Xiaoling 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
  9. pmc TNF-alpha induces leukemic clonal evolution ex vivo in Fanconi anemia group C murine stem cells
    June 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
  10. pmc Rac1 and Rac2 GTPases are necessary for early erythropoietic expansion in the bone marrow but not in the spleen
    Theodosia 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

Research Grants

Detail Information

Publications81

  1. ncbi request reprint The role of chemokine activation of Rac GTPases in hematopoietic stem cell marrow homing, retention, and peripheral mobilization
    Jose A Cancelas
    Division of Experimental Hematology, Cincinnati Children s Research Foundation, Cincinnati, Ohio 45215, USA
    Exp Hematol 34:976-85. 2006
    ....
  2. ncbi request reprint Medicine. Gene therapy--new challenges ahead
    David 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...
  3. ncbi request reprint An international conversation on Stem Cell Gene Therapy. 4th Stem Cell Conference on Stem Cell Gene Therapy, Thessaloniki, Greece, 13-17 September 2007
    David 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
  4. pmc Children are not little adults: just ask their hematopoietic stem cells
    David 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...
  5. ncbi request reprint Gene therapy in the treatment of Fanconi anemia, a progressive bone marrow failure syndrome
    David 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...
  6. pmc Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence
    Xiaoling 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...
  7. pmc Cdc42 critically regulates the balance between myelopoiesis and erythropoiesis
    Linda 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...
  8. pmc Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A
    Xiaoling 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...
  9. pmc TNF-alpha induces leukemic clonal evolution ex vivo in Fanconi anemia group C murine stem cells
    June 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...
  10. pmc Rac1 and Rac2 GTPases are necessary for early erythropoietic expansion in the bone marrow but not in the spleen
    Theodosia 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...
  11. pmc Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential
    Haiming 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...
  12. pmc Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and chemotaxis of hematopoietic progenitor cells
    Hee 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...
  13. ncbi request reprint Rac2-deficient hematopoietic stem cells show defective interaction with the hematopoietic microenvironment and long-term engraftment failure
    Michael 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...
  14. pmc Signaling and cytoskeletal requirements in erythroblast enucleation
    Diamantis 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
    ....
  15. ncbi request reprint Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization
    Jose A Cancelas
    Hoxworth Blood Center, University of Cincinnati Medical Center, 3130 Highland Avenue, Cincinnati, Ohio, 45267, USA
    Nat Med 11:886-91. 2005
    ....
  16. ncbi request reprint Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease
    Emily 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...
  17. doi request reprint Rho GTPases and regulation of hematopoietic stem cell localization
    David 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...
  18. pmc Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of fetal liver with definitive hematopoietic progenitor cells
    Gabriel 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...
  19. ncbi request reprint Inhibition of RhoA GTPase activity enhances hematopoietic stem and progenitor cell proliferation and engraftment
    Gabriel 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...
  20. doi request reprint FIP1L1/PDGFRalpha synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome
    Yoshiyuki 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...
  21. ncbi request reprint Genetic deletion of Rac1 GTPase reveals its critical role in actin stress fiber formation and focal adhesion complex assembly
    Fukun Guo
    Division of Experimental Hematology, Children s Hospital Research Foundation, University of Cincinnati, Cincinnati, Ohio 45229, USA
    J Biol Chem 281:18652-9. 2006
    ....
  22. pmc Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment
    Lei 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...
  23. ncbi request reprint Importance of murine study design for testing toxicity of retroviral vectors in support of phase I trials
    Elke Will
    Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    Mol Ther 15:782-91. 2007
    ....
  24. ncbi request reprint Rac2 regulates neutrophil chemotaxis, superoxide production, and myeloid colony formation through multiple distinct effector pathways
    Dirk 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...
  25. pmc RhoH regulates subcellular localization of ZAP-70 and Lck in T cell receptor signaling
    Hee 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...
  26. doi request reprint Rapid lentiviral transduction preserves the engraftment potential of Fanca(-/-) hematopoietic stem cells
    Lars 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...
  27. ncbi request reprint Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils
    Marie 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...
  28. doi request reprint Reciprocal relationship between O6-methylguanine-DNA methyltransferase P140K expression level and chemoprotection of hematopoietic stem cells
    Michael 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...
  29. pmc Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemia
    Benjamin 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...
  30. ncbi request reprint RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling and thymocyte development
    Yi 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...
  31. ncbi request reprint Stem cell collection and gene transfer in Fanconi anemia
    Patrick 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...
  32. ncbi request reprint 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...
  33. pmc Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton
    Theodosia 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...
  34. pmc Identification and characterization of mutations in FANCL gene: a second case of Fanconi anemia belonging to FA-L complementation group
    Abdullah 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...
  35. doi request reprint Rho GTPases in hematopoietic stem cell functions
    Jose 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...
  36. pmc Live and let die: in vivo selection of gene-modified hematopoietic stem cells via MGMT-mediated chemoprotection
    Michael 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
    ....
  37. ncbi request reprint A rapid method for retrovirus-mediated identification of complementation groups in Fanconi anemia patients
    Saurabh 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...
  38. ncbi request reprint Rational design and applications of a Rac GTPase-specific small molecule inhibitor
    Huzoor 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...
  39. ncbi request reprint HOXB4 inhibits cell growth in a dose-dependent manner and sensitizes cells towards extrinsic cues
    Elke 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...
  40. ncbi request reprint Rac1 GTPase regulates cell genomic stability and senescence
    Marcella 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...
  41. ncbi request reprint Structure-function based design of small molecule inhibitors targeting Rho family GTPases
    Nicolas Nassar
    Division of Experimental Hematology, Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Curr Top Med Chem 6:1109-16. 2006
    ....
  42. pmc Rac2, a hematopoiesis-specific Rho GTPase, specifically regulates mast cell protease gene expression in bone marrow-derived mast cells
    Yi Gu
    Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    Mol Cell Biol 22:7645-57. 2002
    ....
  43. ncbi request reprint Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases
    Yi 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...
  44. pmc Lenti in red: progress in gene therapy for human hemoglobinopathies
    Christof 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...
  45. pmc The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease
    Yoshiyuki 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...
  46. ncbi request reprint 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...
  47. pmc Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survival
    Kyung 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...
  48. ncbi request reprint 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
  49. pmc Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M
    Thiyam 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...
  50. pmc Inflammatory reactive oxygen species-mediated hemopoietic suppression in Fancc-deficient mice
    Daniel 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...
  51. pmc Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells
    Feng 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...
  52. ncbi request reprint 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 cells
    Bai 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...
  53. ncbi request reprint Chemotherapy for myeloid malignancy in children with Fanconi anemia
    Parinda 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...
  54. ncbi request reprint In vivo selection of human hematopoietic cells in a xenograft model using combined pharmacologic and genetic manipulations
    Karen 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
    ....
  55. doi request reprint Oxandrolone for the treatment of bone marrow failure in Fanconi anemia
    Susan R Rose
    Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio Division of Endocrinology, Stanford University School of Medicine, Stanford, California
    Pediatr Blood Cancer 61:11-9. 2014
    ....
  56. ncbi request reprint A rare complex DNA rearrangement in the murine Steel gene results in exon duplication and a lethal phenotype
    Saurabh 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...
  57. ncbi request reprint RAC2 GTPase deficiency and myeloid cell dysfunction in human and mouse
    Yi 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...
  58. ncbi request reprint A theoretically optimized method for cord blood stem cell cryopreservation
    Erik 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...
  59. ncbi request reprint Role of p38 and ERK MAP kinase in proliferation of erythroid progenitors in response to stimulation by soluble and membrane isoforms of stem cell factor
    Reuben 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...
  60. pmc Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development
    Fukun 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...
  61. ncbi request reprint Comparison of three retroviral vector systems for transduction of nonobese diabetic/severe combined immunodeficiency mice repopulating human CD34+ cord blood cells
    Cordula Leurs
    Klinik für Pädiatrische Hämatologie und Onkologie, Zentrum fur Kinderheilkunde, Heinrich Heine Universitat, 40225 Dusseldorf, Germany
    Hum Gene Ther 14:509-19. 2003
    ..These data demonstrate that vectors based on FVs warrant further investigation and development for medical use...
  62. ncbi request reprint Gene therapy advances but struggles to interpret safety data in small animal models
    David A Williams
    Mol Ther 13:1027-8. 2006
  63. pmc CXCL9 inhibits eosinophil responses by a CCR3- and Rac2-dependent mechanism
    Patricia 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...
  64. ncbi request reprint The Rac2 guanosine triphosphatase regulates B lymphocyte antigen receptor responses and chemotaxis and is required for establishment of B-1a and marginal zone B lymphocytes
    Ben 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...
  65. ncbi request reprint New AAV serotypes may broaden the therapeutic pipeline to human gene therapy
    David A Williams
    Mol Ther 13:1-2. 2006
  66. ncbi request reprint Rac2-deficient mice display perturbed T-cell distribution and chemotaxis, but only minor abnormalities in T(H)1 responses
    Ben 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...
  67. ncbi request reprint Phenotypic correction of primary Fanconi anemia T cells with retroviral vectors as a diagnostic tool
    Helmut 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...
  68. ncbi request reprint The TRQQKRP motif located near the C-terminus of Rac2 is essential for Rac2 biologic functions and intracellular localization
    Wen 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...
  69. ncbi request reprint Hematoprotection and enrichment of transduced cells in vivo after gene transfer of MGMT(P140K) into hematopoietic stem cells
    Michael 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...
  70. pmc Methylguanine methyltransferase-mediated in vivo selection and chemoprotection of allogeneic stem cells in a large-animal model
    Tobias Neff
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 1024, USA
    J Clin Invest 112:1581-8. 2003
    ....
  71. pmc Stable differentiation and clonality of murine long-term hematopoiesis after extended reduced-intensity selection for MGMT P140K transgene expression
    Claudia R Ball
    National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany
    Blood 110:1779-87. 2007
    ....
  72. ncbi request reprint Vector insertion, mutagenesis and transgene toxicity
    David A Williams
    Mol Ther 14:457. 2006
  73. ncbi request reprint Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling
    Marita 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...
  74. ncbi request reprint Chance or necessity? Insertional mutagenesis in gene therapy and its consequences
    Christopher 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...
  75. ncbi request reprint Side effects of retroviral gene transfer into hematopoietic stem cells
    Christopher Baum
    Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Blood 101:2099-114. 2003
    ....
  76. ncbi request reprint Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts
    Charles 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...
  77. pmc Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling
    Ximei Wu
    Department of Medicine, Washington University Medical School, St Louis, MO 63110, USA
    Cell 133:340-53. 2008
    ....
  78. doi request reprint Progress reported in two studies of clinical gene transfer into the retina
    David A Williams
    Mol Ther 16:1181. 2008
  79. doi request reprint Foamy virus vectors come of age
    David A Williams
    Mol Ther 16:635-6. 2008
  80. ncbi request reprint Lentiviral vectors pseudotyped with murine ecotropic envelope: increased biosafety and convenience in preclinical research
    Axel Schambach
    Department of Hematology, Hemostaseology and Oncology, Hannover Medical School, Germany
    Exp Hematol 34:588-92. 2006
    ..However, this method has found little acceptance, despite potential advantages...
  81. ncbi request reprint A "vector drain" in US gene therapy development?
    Michel Sadelain
    Mol Ther 16:801-2. 2008

Research Grants6

  1. Chemoresistance and Stem Cell Selection
    David 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. ..
  2. Novel Molecular and Cellular Therapies in Fanconi Anemia
    David 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. ..
  3. Rac protein in hematopoietic cell survival and function
    David Williams; Fiscal Year: 2007
    ....