Our long-term research goals are to understand the mechanisms that regulate stem cell fate decisions. To ensure a life-long supply of blood and immune cells, the hematopoietic stem cell (HSC) must balance self-renewal with differentiation by responding properly to complex and dynamic inputs from the environment. The goal of this proposal is to develop two new mouse models that will serve as important tools for dissecting the intrinsic and extrinsic mechanisms that govern HSC function. These new models will enable us to pursue the mechanisms regulating hematopoietic homeostasis, the role of niches in HSC fate decisions and engraftment, how radiation-induced effects influence these processes, and a range of other questions that cannot be answered by existing methods. The outcomes will facilitate ex vivo HSC expansion and guide strategies for improving the safety and efficiency of HSC transplantation therapies. .
This proposal will investigate mechanisms regulating the function of blood-forming stem cells. The findings will be used to improve the treatment of cancer and disorders of the blood and immune system.
| Larsen, Michele Campaigne; N'Jai, Alhaji U; Alexander, David L et al. (2016) Cyp1b1-mediated suppression of lymphoid progenitors in bone marrow by polycyclic aromatic hydrocarbons coordinately impacts spleen and thymus: a selective role for the Ah Receptor. Pharmacol Res Perspect 4:e00245 |
| Perez-Cunningham, Jessica; Boyer, Scott W; Landon, Mark et al. (2016) Hematopoietic stem cell-specific GFP-expressing transgenic mice generated by genetic excision of a pan-hematopoietic reporter gene. Exp Hematol 44:755-764.e1 |
| Zovein, Ann C; Forsberg, E Camilla (2015) Hematopoietic development at high altitude: blood stem cells put to the test. Development 142:1728-32 |
| Smith-Berdan, Stephanie; Nguyen, Andrew; Hong, Matthew A et al. (2015) ROBO4-mediated vascular integrity regulates the directionality of hematopoietic stem cell trafficking. Stem Cell Reports 4:255-68 |
