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Researcher | Research Overview

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Research in the Williams' laboratory focuses on understanding the biology of the hematopoietic stem cells, including development of gene transfer methods for application in the treatment of severe genetic diseases of the blood system by gene therapy.

The major interest of the Williams laboratory is focused on the biology of hematopoietic stem cells. This work has focused on understanding the interaction of hematopoietic stem cells with the bone marrow and abnormalities of these interactions which are associated with leukemia.

The laboratory is focusing on analysis of the function of members of the Rho GTPase family, specifically Rac and RhoH in blood cell development and function. Rho GTPases are members of the Ras superfamily and act as molecular switches to control multiple cell processes, such as migration, phagocytosis, cell cycle progression, and apoptosis via activation of multiple kinase pathways. Using gene targeted transgenic mice, and a variety of specialized bone marrow culture methods, Dr. Williams' laboratory is defining the essential roles of Rho GTPases in blood cell functions, particularly in response to integrin ligation and activation of chemokine and cytokine receptors. Current work is dissecting the upstream activators and downstream effectors of Rho GTPase in hematopoietic stem cells.

The laboratory has demonstrated that Rac GTPases are key regulators of the engraftment and mobilization functions of hematopoietic stem cells. Increasing focus has been on the dysregulated function of these key molecular switches in leukemia. Recent data from the Williams’ laboratory implicates both Rac and Rho in acute and chronic leukemias and current efforts include development of new inhibitors of these molecular targets and validation studies of these molecules in leukemia model systems. In addition, this basic work has helped to define the molecular abnormalities in two rare immunodeficiency diseases, Leukocyte Adhesion Deficiency Type IV (due to RAC2 mutations) and Epidermodysplasia Verruciformis (due to mutations in RHOH).

Much of the basic information derived from these studies is also being applied to improve the methods of gene transfer into hematopoietic stem cells using retrovirus and lentivirus vectors.
Dr. Williams is serving as sponsor investigator for a number of human gene therapy trials at CHB, including in SCID-X1, Wiskott-Aldrich Disease, Childhood Cerebral Adrenoleukodystropy and a trial in sickle cell disease targeting the transcription factor BCL11a.

Major goals of research:

  • To further understand the role Rho GTPases as key regulatory switches that control stem cell adhesion, migration and survival/proliferation.
  • Continue to develop and advance the use viral vectors for gene transfer into hematopoietic stem cells with the purpose of advancing clinical gene therapy trials.
  • To advance the translation of basic research into novel therapeutic applications.


  • A phase 1/2 clinical trial in Blood reports encouraging results with gene therapy in patients with Wiskott-Aldrich syndrome, using a self-inactivating lentiviral vector. Click here to read  more
  • A study in Nature Communications confirms that gene therapy targeting BCL11A for sickle-cell disease boosted patients’ non-sickling fetal hemoglobin while reducing adult hemoglobin. Click here to read more

Researcher | Research Background

Dr. Williams has won numerous prestigious awards for his research, including: the Dameshek Award and the Frank Oski Award of the American Society of Hematology for research in hematology; the Donald Metcalf Award from the International Society for Hematology and Stem Cells for contributions to the field; the E. Mead Johnson Award of the Society for Pediatric Research for research in pediatrics and most recently the Outstanding Achievement Award of the American Society of Gene and Cell Therapy (2011). He was an Investigator of the Howard Hughes Medical Institute for 16 years and is a member of the National Academy of Sciences Institute of Medicine. He has been continuously funded by the National Institutes of Health since 1986. Dr. Williams has multiple patents, several of which have been licensed to pharmaceutical and biotechnology.

Dr. Williams' Clinical Page


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Dr. David Williams is the recipient of the 2023 ASGCT Founder’s Award

Researcher | Publications