Abstract

Public Health Relevance

Cdc42 GTPase and leukemia stem cells have emerged as potential anti-cancer therapeutic targets by recent studies. The proposed work will pursue genetic and pharmacologic targeting of Cdc42 to benefit leukemia therapy by introducing a novel concept that targeting Cdc42 in leukemia stem cells could result in their mobilization from the niche and this could serve as a new means in combinatory therapy. The studies will translate the mechanistic information obtained from the decades-long biochemical, cell biological, and genetic studies of Cdc42 and leukemia into future therapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA150547-02
Application #
8042683
Study Section
Special Emphasis Panel (ZRG1-VH-D (02))
Program Officer
Mufson, R Allan
Project Start
2010-03-10
Project End
2015-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
2
Fiscal Year
2011
Total Cost
$307,531
Indirect Cost

  Institution

Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229

  Publications

Du, Wei; Liu, Wei; Mizukawa, Benjamin et al. (2018) A non-myeloablative conditioning approach for long-term engraftment of human and mouse hematopoietic stem cells. Leukemia 32:2041-2046
Lin, Yuan; Zheng, Yi (2015) Approaches of targeting Rho GTPases in cancer drug discovery. Expert Opin Drug Discov 10:991-1010
Chang, Kyung Hee; Nayak, Ramesh C; Roy, Swarnava et al. (2015) Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem cells/progenitors through endothelial AT?R and cytoskeletal dysregulation. Nat Commun 6:5914
Zandvakili, Inuk; Davis, Ashley Kuenzi; Hu, Guodong et al. (2015) Loss of RhoA Exacerbates, Rather Than Dampens, Oncogenic K-Ras Induced Lung Adenoma Formation in Mice. PLoS One 10:e0127923
Evelyn, Chris R; Duan, Xin; Biesiada, Jacek et al. (2014) Rational design of small molecule inhibitors targeting the Ras GEF, SOS1. Chem Biol 21:1618-28
Shang, Xun; Marchioni, Fillipo; Evelyn, Chris R et al. (2013) Small-molecule inhibitors targeting G-protein-coupled Rho guanine nucleotide exchange factors. Proc Natl Acad Sci U S A 110:3155-60
Zhou, Xuan; Florian, Maria Carolina; Arumugam, Paritha et al. (2013) RhoA GTPase controls cytokinesis and programmed necrosis of hematopoietic progenitors. J Exp Med 210:2371-85
Melendez, Jaime; Liu, Ming; Sampson, Leesa et al. (2013) Cdc42 coordinates proliferation, polarity, migration, and differentiation of small intestinal epithelial cells in mice. Gastroenterology 145:808-19
Zhou, Xuan; Zheng, Yi (2013) Cell type-specific signaling function of RhoA GTPase: lessons from mouse gene targeting. J Biol Chem 288:36179-88
Shang, Xun; Marchioni, Fillipo; Sipes, Nisha et al. (2012) Rational design of small molecule inhibitors targeting RhoA subfamily Rho GTPases. Chem Biol 19:699-710

Showing the most recent 10 out of 16 publications