Lab
Damm Lab
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Statement of Research Interest
Hematopoietic stem cells (HSCs) generate all blood cell lineages throughout life and are used in transplant therapies for treatment of blood diseases, including leukemias and non-malignant blood diseases like sickle cell anemia. HSCs develop from a specialized hemogenic endothelium that lines the floor of the primitive dorsal aorta. These cells transition into HSCs after receiving signals from neighboring cells. Our previous work has found that SNS precursor cells, which are derivatives of the trunk neural crest, communicate required signals to the hemogenic endothelium for the development of HSCs. Importantly, our work has shown that development of HSCs and the SNS likely require reciprocal signals resulting in the activation of the key transcriptional programs underlying their development.
Understanding these signals and transcriptional programs is biomedically important for two main reasons. (1) The generation of HSCs in vitro from adult pluripotent stem cells is a major biomedical objective that has potential to alleviate donor compatibility problems and improve tools for gene therapy approaches for the treatment of blood diseases. However, it has not been possible to generate bona fide HSCs in vitro, most likely because the full set of developmental signals has not been identified. Characterizing the in vivo molecular control of HSC development is thus an important prerequisite for the in vitro generation of HSCs. (2) The dysregulation of normal SNS development is associated with diseases like high-grade neuroblastoma, of which the survival rate is less than 50%. Studying the molecular control of SNS development will improve our understanding of neuronal differentiation, cell proliferation and cell survival and how these processes cooperate with oncogenic mutations driving tumorigenesis.
My laboratory works at the intersection of neural, blood and vascular development and takes advantage of unique transgenic zebrafish and zebrafish disease models to understand the intrinsic and extrinsic programming of the integrated development of the sympathetic nervous, vascular and blood systems.
Understanding these signals and transcriptional programs is biomedically important for two main reasons. (1) The generation of HSCs in vitro from adult pluripotent stem cells is a major biomedical objective that has potential to alleviate donor compatibility problems and improve tools for gene therapy approaches for the treatment of blood diseases. However, it has not been possible to generate bona fide HSCs in vitro, most likely because the full set of developmental signals has not been identified. Characterizing the in vivo molecular control of HSC development is thus an important prerequisite for the in vitro generation of HSCs. (2) The dysregulation of normal SNS development is associated with diseases like high-grade neuroblastoma, of which the survival rate is less than 50%. Studying the molecular control of SNS development will improve our understanding of neuronal differentiation, cell proliferation and cell survival and how these processes cooperate with oncogenic mutations driving tumorigenesis.
My laboratory works at the intersection of neural, blood and vascular development and takes advantage of unique transgenic zebrafish and zebrafish disease models to understand the intrinsic and extrinsic programming of the integrated development of the sympathetic nervous, vascular and blood systems.
Lab Members
| Williams, Bradley |