This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project is centered on the genetic and molecular control of E3 ubiquitin ligases in stem cell differentiation and neoplasia. The underlying hypothesis, based on the project leader's work recently published in PNAS (2010) and about to be published in Nature Immunology, provides an innovative approach to stem cell differentiation. The hypothesis states that the presence of c-Cbl ring finger mutant protein in HSCs results in altered signal transduction pathways and thereby causes transformation of normal HSCs into leukemic stem cells. In order to prove or disprove this hypothesis, the project leader has developed the following specific aims: 1) Investigate the myeloid differentiation defects in the c-Cbl -/- mice. 2): Identify the hematopoietic compartment that causes AML in c-Cbl A/- mice. 3) Decipher the dominant negative functions of c-Cbl Ring Finger mutant protein in the development of acute myelogenous leukemia (AML). 4) Dissect the requirement of c-Kit/PI3K/AKT/Erk signal transduction pathways in the development of myeloid leukemia in Cbl A/- mice. Overall, this work promises to provide novel ways to understand stem cell differentiation and may also provide directions for therapeutics that may aid the treatment of patients with c-Cbl mutations.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR018757-09
Application #
8360045
Study Section
Special Emphasis Panel (ZRR1-RI-6 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
9
Fiscal Year
2011
Total Cost
$12,623
Indirect Cost
Name
Roger Williams Hospital
Department
Type
DUNS #
625899281
City
Providence
State
RI
Country
United States
Zip Code
02908
Kim, Joseph W; Vang, Souriya; Luo, John Zq et al. (2017) Effects of bone marrow on the microenvironment of the human pancreatic islet: A Protein Profile Approach. Mol Cell Endocrinol 450:32-42
Luo, John Z Q; Kim, Joseph W; Luo, LuGuang (2016) EFFECTS OF GINSENG AND ITS FOUR PURIFED GINSENOSIDES (Rb2, Re, Rg1, Rd) ON HUMAN PANCREATIC ISLET ? CELL IN VITRO. Eur J Pharm Med Res 3:110-119
Tang, Jin Bo; Wu, Ya Fang; Cao, Yi et al. (2016) Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons. Sci Rep 6:20643
Kim, Joseph W; Luo, John Z; Luo, Luguang (2015) The Biochemical Cascades of the Human Pancreatic ?-Cells: The Role of MicroRNAs. J Bioanal Biomed 7:
Luo, Lu Guang; Xiong, Fang; Ravassard, Philippe et al. (2015) Human Bone Marrow Subpopulations Sustain Human Islet Function and Viability In vitro. Br J Med Med Res 8:576-587
Ilgun, Handenur; Kim, Joseph William; Luo, LuGuang (2015) Adult Stem Cells and Diabetes Therapy. J Stem Cell Res Transplant 2:
Bartos, Adrian; Dubielecka, Patrycja M (2014) The emerging role of Bcr-Abl-induced cystoskeletal remodeling in systemic persistence of leukemic stem cells. Curr Drug Deliv 11:582-91
Chorzalska, A; Dubielecka, P M (2014) New Abelson interactor-1 (Abi-1)-driven mechanism of acquired drug resistance. Leuk Suppl 3:S7-8
Chorzalska, A; Salloum, I; Shafqat, H et al. (2014) Low expression of Abelson interactor-1 is linked to acquired drug resistance in Bcr-Abl-induced leukemia. Leukemia 28:2165-77
Michalczyk, Izabela; Sikorski, Aleksander F; Kotula, Leszek et al. (2013) The emerging role of protein kinase C? in cytoskeletal signaling. J Leukoc Biol 93:319-27

Showing the most recent 10 out of 90 publications