David A. Williams

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威廉姆斯实验室的研究重点是理解造血干细胞的生物学，包括开发基因转移方法，用于通过基因治疗治疗血液系统严重遗传疾病。

威廉姆斯实验室的主要兴趣集中在造血干细胞的生物学上。这项工作集中在理解造血干细胞与骨髓的相互作用以及与白血病有关的这些相互作用的异常。

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.

该实验室表明，RAC GTPases是造血干细胞的植入和动员功能的关键调节剂。这些关键分子开关在白血病中的功能失调的功能不足。威廉姆斯实验室的最新数据暗示了RAC和RHO在急性和慢性白血病中以及当前的努力包括开发这些分子靶标的新抑制剂以及对白血病模型系统中这些分子的验证研究。此外，这项基本工作有助于确定两种罕见的免疫缺陷疾病，白细胞粘附缺乏IV型（由于RAC2突变）和表皮异常发育不良（由于RHOH突变）的分子异常。

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 planned 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.