David A. Williams, MD
Chief, Division of Hematology/Oncology, Boston Children’s Hospital; Associate Chairman, Department of Pediatric Oncology, Dana-Farber Cancer Institute; Institute Physician
Leland Fikes Professor of Pediatrics, Harvard Medical School
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David A. Williams, MD
Chief, Division of Hematology/Oncology, Boston Children’s Hospital; Associate Chairman, Department of Pediatric Oncology, Dana-Farber Cancer Institute; Institute Physician
Leland Fikes Professor of Pediatrics, Harvard Medical School
Medical Services
Languages
English
Education
Medical School
Indiana University School of Medicine
1979
Indianapolis
IN
Internship
Cincinnati's Children's Hospital Medical Center
1980
Cincinnati
OH
Residency
Cincinnati's Children's Hospital Medical Center
1982
Cincinnati
OH
Fellowship
Hematology/Oncology
Boston Children's Hospital/Dana-Farber Cancer Institute
1985
Boston
MA
Media
Research
Gene therapy for sickle cell disease: The journey to a new treatment
Award
Dr. David Williams is the recipient of the 2023 ASGCT Founder’s Award
Certifications
American Board of Pediatrics (General)
Professional History
Dr. David A. Williams is a graduate of Indiana State University and Indiana University School of Medicine. After training in Pediatrics at Cincinnati Children's Hospital Medical Center, Dr. Williams completed fellowship training in Pediatric Hematology/Oncology at Dana-Farber/Boston Children's. He completed his research training here and at the Whitehead Institute at the Massachusetts Institute of Technology. He then became a faculty member at Harvard Medical School and of the Howard Hughes Medical Institute (HHMI).
Publications
Eltrombopag in combination with immunosuppressive therapy in pediatric severe aplastic anemia: Phase 2 ESCALATE trial. View Abstract
Ex vivo modification of hematopoietic stem and progenitor cells for gene therapy. View Abstract
Myelodysplasia after Lentiviral Gene Therapy. Reply. View Abstract
Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells. View Abstract
UM171 enhances fitness and engraftment of gene-modified hematopoietic stem cells from patients with sickle cell disease. View Abstract
Engineered packaging cell line for the enhanced production of baboon-enveloped retroviral vectors. View Abstract
Regulated GATA1 expression as a universal gene therapy for Diamond-Blackfan anemia. View Abstract
Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy. View Abstract
Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy. View Abstract
A novel high-titer, bifunctional lentiviral vector for autologous hematopoietic stem cell gene therapy of sickle cell disease. View Abstract
Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease. View Abstract
Outcomes of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. View Abstract
Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells. View Abstract
Hematopoietic stem-cell gene therapy is associated with restored white matter microvascular function in cerebral adrenoleukodystrophy. View Abstract
Future Directions and Resource Needs for National Heart, Lung, and Blood Institute (NHLBI) Gene Therapy Research: A Report of an NHLBI Workshop. View Abstract
Secondary Neoplasms After Hematopoietic Cell Transplant for Sickle Cell Disease. View Abstract
Replication competent retrovirus testing (RCR) in the National Gene Vector Biorepository: No evidence of RCR in 1,595 post-treatment peripheral blood samples obtained from 60 clinical trials. View Abstract
Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C, p.Leu97Pro (hemoglobin Wareham). View Abstract
The long road traveled in hematopoietic stem cell gene therapy. View Abstract
Development of a double shmiR lentivirus effectively targeting both BCL11A and ZNF410 for enhanced induction of fetal hemoglobin to treat ß-hemoglobinopathies. View Abstract
Validation of a small molecule inhibitor of PDE6D-RAS interaction with favorable anti-leukemic effects. View Abstract
Clonal hematopoiesis in sickle cell disease. View Abstract
Deletion of murine Rhoh leads to de-repression of Bcl-6 via decreased KAISO levels and accelerates a malignancy phenotype in a murine model of lymphoma. View Abstract
Investigational curative gene therapy approaches to sickle cell disease. View Abstract
Restored Macrophage Function Ameliorates Disease Pathophysiology in a Mouse Model for IL10 Receptor-deficient Very Early Onset Inflammatory Bowel Disease. View Abstract
Evidence generation and reproducibility in cell and gene therapy research: A call to action. View Abstract
Mechanisms underlying genetic susceptibility to multisystem inflammatory syndrome in children (MIS-C). View Abstract
Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease. View Abstract
A study assessing the feasibility of randomization of pediatric and young adult patients between matched unrelated donor bone marrow transplantation and immune-suppressive therapy for newly diagnosed severe aplastic anemia: A joint pilot trial of the North American Pediatric Aplastic Anemia Consortium and the Pediatric Transplantation and Cellular Therapy Consortium. View Abstract
The Changing Face of Adrenoleukodystrophy. View Abstract
Peripheral blood smears of children with multisystem inflammatory syndrome demonstrate prominence of early myeloid forms with morphologic evidence of toxic change. View Abstract
Children's rare disease cohorts: an integrative research and clinical genomics initiative. View Abstract
Children's rare disease cohorts: an integrative research and clinical genomics initiative. View Abstract
Current and future gene therapies for hemoglobinopathies. View Abstract
Infantile Myelofibrosis and Myeloproliferation with CDC42 Dysfunction. View Abstract
Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy. View Abstract
Lentiviral gene therapy for X-linked chronic granulomatous disease. View Abstract
Highly efficient therapeutic gene editing of human hematopoietic stem cells. View Abstract
Two Decades of Molecular Therapy and a 35-Year Personal View of Changes in Gene Therapy. View Abstract
Successful hematopoietic stem cell mobilization and apheresis collection using plerixafor alone in sickle cell patients. View Abstract
T cell dynamics and response of the microbiota after gene therapy to treat X-linked severe combined immunodeficiency. View Abstract
The pseudokinase MLKL activates PAD4-dependent NET formation in necroptotic neutrophils. View Abstract
DROSHA Knockout Leads to Enhancement of Viral Titers for Vectors Encoding miRNA-Adapted shRNAs. View Abstract
Gene Therapy for Cerebral Adrenoleukodystrophy. View Abstract
The gp130 Cytokine Interleukin-11 Regulates Engraftment of Vav1-/- Hematopoietic Stem and Progenitor Cells in Lethally Irradiated Recipients. View Abstract
Self-Guided Online Cognitive Behavioral Strategies for Chemotherapy-Induced Peripheral Neuropathy: A Multicenter, Pilot, Randomized, Wait-List Controlled Trial. View Abstract
A key role for Rac and Pak signaling in neutrophil extracellular traps (NETs) formation defines a new potential therapeutic target. View Abstract
Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy. View Abstract
Enhancement of mouse hematopoietic stem/progenitor cell function via transient gene delivery using integration-deficient lentiviral vectors. View Abstract
The 2017 ASPHO distinguished career award goes to Holcombe E. Grier, MD. View Abstract
Evolving Gene Therapy in Primary Immunodeficiency. View Abstract
Rapid Lentiviral Transduction Preserves the Engraftment Potential of Fanca-/- Hematopoietic Stem Cells. View Abstract
AAV and Insertional Mutagenesis. View Abstract
Of Mouse Models and Men. View Abstract
Molecular Therapy Moves on to a New Editor-in-Chief. View Abstract
Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype. View Abstract
Assessment of physical function and participation in chronic pain clinical trials: IMMPACT/OMERACT recommendations. View Abstract
RhoH participates in a multi-protein complex with the zinc finger protein kaiso that regulates both cytoskeletal structures and chemokine-induced T cells. View Abstract
Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa. View Abstract
Mathematical modeling of erythrocyte chimerism informs genetic intervention strategies for sickle cell disease. View Abstract
The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. View Abstract
Mechanism of Drug-Drug Interactions Between Warfarin and Statins. View Abstract
The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. View Abstract
p21-activated kinase 2 regulates HSPC cytoskeleton, migration, and homing via CDC42 activation and interaction with ß-Pix. View Abstract
Response to correspondence: Flow cytometric quantification of neutrophil extracellular traps: Limitations of the methodological approach by Ciepiela et al. View Abstract
Comparison of enzyme kinetics of warfarin analyzed by LC-MS/MS QTrap and differential mobility spectrometry. View Abstract
Flow cytometric assay for direct quantification of neutrophil extracellular traps in blood samples. View Abstract
miRNA-embedded shRNAs for Lineage-specific BCL11A Knockdown and Hemoglobin F Induction. View Abstract
Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy. View Abstract
A modified ?-retrovirus vector for X-linked severe combined immunodeficiency. View Abstract
Unexpected help: mTOR meets lentiviral vectors. View Abstract
Genetic deletion of the GATA1-regulated protein a-synuclein reduces oxidative stress and nitric oxide synthase levels in mature erythrocytes. View Abstract
Charting a clear path: the ASGCT Standardized Pathways Conference. View Abstract
Loss of function of TET2 cooperates with constitutively active KIT in murine and human models of mastocytosis. View Abstract
Concise review: lessons learned from clinical trials of gene therapy in monogenic immunodeficiency diseases. View Abstract
Retroviral transduction of murine and human hematopoietic progenitors and stem cells. View Abstract
Curing genetic disease with gene therapy. View Abstract
Diagnosis and treatment of pediatric acquired aplastic anemia (AAA): an initial survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC). View Abstract
A unique carboxyl-terminal insert domain in the hematopoietic-specific, GTPase-deficient Rho GTPase RhoH regulates post-translational processing. View Abstract
Oxandrolone for the treatment of bone marrow failure in Fanconi anemia. View Abstract
Broadening the indications for hematopoietic stem cell genetic therapies. View Abstract
Depletion of Jak2V617F myeloproliferative neoplasm-propagating stem cells by interferon-a in a murine model of polycythemia vera. View Abstract
The Rac GTPase effector p21-activated kinase is essential for hematopoietic stem/progenitor cell migration and engraftment. View Abstract
Enough is indeed enough: ACGME required changes in pediatric training. View Abstract
Induced pluripotent stem cells as a tool for gaining new insights into Fanconi anemia. View Abstract
CTC1 Mutations in a patient with dyskeratosis congenita. View Abstract
RhoH is critical for cell-microenvironment interactions in chronic lymphocytic leukemia in mice and humans. View Abstract
Signaling and cytoskeletal requirements in erythroblast enucleation. View Abstract
Overcoming reprogramming resistance of Fanconi anemia cells. View Abstract
In vivo enrichment of cytidine deaminase gene-modified hematopoietic cells by prolonged cytosine-arabinoside application. View Abstract
Rac signaling in osteoblastic cells is required for normal bone development but is dispensable for hematopoietic development. View Abstract
PTEN negatively regulates engulfment of apoptotic cells by modulating activation of Rac GTPase. View Abstract
Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemia. View Abstract
Differential niche and Wnt requirements during acute myeloid leukemia progression. View Abstract
Guanine nucleotide exchange factor Vav1 regulates perivascular homing and bone marrow retention of hematopoietic stem and progenitor cells. View Abstract
Stem cell gene therapy for fanconi anemia: report from the 1st international Fanconi anemia gene therapy working group meeting. View Abstract
Out of harm's way. View Abstract
Transatlantic consortium spotlights need for changes in gene therapy trials. View Abstract
Training program in cancer and blood diseases: Pediatric Hematology/Oncology Fellowship Program, Children's Hospital Boston/Dana-Farber Cancer Institute. View Abstract
Gaining the hard yard: pre-clinical evaluation of lentiviral-mediated gene therapy for the treatment of beta-thalassemia. View Abstract
The American Society of Pediatric Hematology/Oncology (ASPHO) 2010 Distinguished Career Award Goes to Dr. Sam Lux. View Abstract
The Apc(min) mouse has altered hematopoietic stem cell function and provides a model for MPD/MDS. View Abstract
Rac GTPases in human diseases. View Abstract
Hematology grants workshop. View Abstract
Rac1 and Rac2 GTPases are necessary for early erythropoietic expansion in the bone marrow but not in the spleen. View Abstract
Correction and apology. View Abstract
National Institutes of Health releases new guidelines on human stem cell research. View Abstract
Gene therapy continues to mature and to face challenges. View Abstract
Rapid development of pluripotent stem cells as a potential therapeutic modality. View Abstract
Recombinant DNA advisory committee updates recommendations on gene transfer for x-linked severe combined immunodeficiency. View Abstract
Finding the needle in the hay stack: hematopoietic stem cells in Fanconi anemia. View Abstract
Progress in genetic therapy for severe combined immunodeficiency associated with adenosine deaminase deficiency. View Abstract
Upping the ante: recent advances in direct reprogramming. View Abstract
Ectopic HOXB4 overcomes the inhibitory effect of tumor necrosis factor-{alpha} on Fanconi anemia hematopoietic stem and progenitor cells. View Abstract
New approaches in the potential treatment of HIV-acquired immunodeficiency disease. View Abstract
ESCGT 2008: progress in clinical gene therapy. View Abstract
mTORC1-dependent and -independent regulation of stem cell renewal, differentiation, and mobilization. View Abstract
Sleeping beauty vector system moves toward human trials in the United States. View Abstract
Reciprocal relationship between O6-methylguanine-DNA methyltransferase P140K expression level and chemoprotection of hematopoietic stem cells. View Abstract
Progress reported in two studies of clinical gene transfer into the retina. View Abstract
Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development. View Abstract
A "vector drain" in US gene therapy development? View Abstract
Rapid lentiviral transduction preserves the engraftment potential of Fanca(-/-) hematopoietic stem cells. View Abstract
Foamy virus vectors come of age. View Abstract
NIH recombinant DNA Advisory Committee continues to ponder adverse event associated with AAV gene therapy trial. View Abstract
Rho GTPases and regulation of hematopoietic stem cell localization. View Abstract
Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of fetal liver with definitive hematopoietic progenitor cells. View Abstract
An international conversation on Stem Cell Gene Therapy. 4th Stem Cell Conference on Stem Cell Gene Therapy, Thessaloniki, Greece, 13-17 September 2007. View Abstract
RAC reviews serious adverse event associated with AAV therapy trial. View Abstract
Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease. View Abstract
Small pituitary size in children with Fanconi anemia. View Abstract
NIH decides against continuing NGVLs in their current form. View Abstract
Chemotherapy for myeloid malignancy in children with Fanconi anemia. View Abstract
Live and let die: in vivo selection of gene-modified hematopoietic stem cells via MGMT-mediated chemoprotection. View Abstract
Are lentivirus vectors safer? View Abstract
Importance of murine study design for testing toxicity of retroviral vectors in support of phase I trials. View Abstract
ASGT advises NIH on funding of gene therapy trials. View Abstract
Stem cell collection and gene transfer in Fanconi anemia. View Abstract
NIH funding of gene therapy trials. View Abstract
Vector insertion, mutagenesis and transgene toxicity. View Abstract
Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton. View Abstract
A pox on your tumor. View Abstract
Inhibition of RhoA GTPase activity enhances hematopoietic stem and progenitor cell proliferation and engraftment. View Abstract
Gene therapy advances but struggles to interpret safety data in small animal models. View Abstract
Lentiviral vectors pseudotyped with murine ecotropic envelope: increased biosafety and convenience in preclinical research. View Abstract
Adventitious mutations in clinical grade vectors: an issue to consider? View Abstract
An emerging consensus on recommendations to facilitate clinical gene transfer. View Abstract
Determination of methenamine, methenamine mandelate and methenamine hippurate in pharmaceutical preparations using ion-exchange HPLC. View Abstract
Simultaneous determination of triamcinolone acetonide and oxymetazoline hydrochloride in nasal spray formulations by HPLC. View Abstract
New AAV serotypes may broaden the therapeutic pipeline to human gene therapy. View Abstract
FDA guidance document on monitoring delayed adverse events a good first start. View Abstract
Promoting translational research in academic health centers: navigating the "roadmap". View Abstract
Equal potency of gammaretroviral and lentiviral SIN vectors for expression of O6-methylguanine-DNA methyltransferase in hematopoietic cells. View Abstract
Gene therapy in the treatment of Fanconi anemia, a progressive bone marrow failure syndrome. View Abstract
A rapid method for retrovirus-mediated identification of complementation groups in Fanconi anemia patients. View Abstract
A balanced decision? Regulatory reaction to the "third case". View Abstract
The NIH roadmap: timing is everything. View Abstract
Real-Time PCR: an Effective Tool for Measuring Transduction Efficiency in Human Hematopoietic Progenitor Cells. View Abstract
Chance or necessity? Insertional mutagenesis in gene therapy and its consequences. View Abstract
Methylguanine methyltransferase-mediated in vivo selection and chemoprotection of allogeneic stem cells in a large-animal model. View Abstract
Medicine. Gene therapy--new challenges ahead. View Abstract
A rare complex DNA rearrangement in the murine Steel gene results in exon duplication and a lethal phenotype. View Abstract
Comparison of three retroviral vector systems for transduction of nonobese diabetic/severe combined immunodeficiency mice repopulating human CD34+ cord blood cells. View Abstract
Side effects of retroviral gene transfer into hematopoietic stem cells. View Abstract
Hematoprotection and enrichment of transduced cells in vivo after gene transfer of MGMT(P140K) into hematopoietic stem cells. View Abstract
Gene Therapy 2000. View Abstract
Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production. View Abstract
Novel human oncogene lbc detected by transfection with distinct homology regions to signal transduction products. View Abstract
Long-term in vivo expression of a murine adenosine deaminase gene in rhesus monkey hematopoietic cells of multiple lineages after retroviral mediated gene transfer into CD34+ bone marrow cells. View Abstract
Restriction of neuroblastoma to the prostate gland in transgenic mice. View Abstract
Retroviral gene transfer of human adenosine deaminase in murine hematopoietic cells: effect of selectable marker sequences on long-term expression. View Abstract
Gene transfer into murine hematopoietic stem cells and bone marrow stromal cells. View Abstract
Long-term expression of human adenosine deaminase in mice transplanted with retrovirus-infected hematopoietic stem cells. View Abstract
Gene therapy of somatic cells: status and prospects. View Abstract
Retrovirus-mediated gene transfer of human adenosine deaminase: expression of functional enzyme in murine hematopoietic stem cells in vivo. View Abstract
Transfer and expression of human ADA in murine hematopoietic stem cells. View Abstract
Retrovirus-mediated transfer of human adenosine deaminase gene sequences into cells in culture and into murine hematopoietic cells in vivo. View Abstract
Somatic gene therapy. Current status and future prospects. View Abstract