The Synthesis and Nanoformulation Core (SNC) will supply ceramide analogs, acid ceramidase (AC) inhibitors, sphingosine kinase inhibitors, and tamoxifen metabolites essential to the members of this Program Project. In addition, the Core will also provide liposomal formulations of C6-ceramide derivatives, acid ceramidase inhibitors, sphingosine kinase inhibitor SKI-178, and tamoxifen metabolites to the Projects 1, 2, 3, and 4, respectively. Furthermore, the Core will also synthesize [^H] AC inhibitors and [^

Public Health Relevance

A successful completion of this Program Project, that is focused on defining the biological basis of dysfunctional sphingoiipid metabolism in AML and new therapeutic targets for molecular and lipidomimetic treatment approaches, requires novel chemical agents. Since the syntheses techniques are beyond the scope and experience of individual Project leaders, the inclusion of SNC in this proposal is highly relevant.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA171983-01A1
Application #
8554598
Study Section
Project Start
2013-09-10
Project End
2018-08-31
Budget Start
2013-09-10
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$150,605
Indirect Cost
$47,317
Name
Pennsylvania State University
Department
Type
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Najima, Yuho; Tomizawa-Murasawa, Mariko; Saito, Yoriko et al. (2016) Induction of WT1-specific human CD8+ T cells from human HSCs in HLA class I Tg NOD/SCID/IL2rgKO mice. Blood 127:722-34
Morad, Samy A F; Ryan, Terence E; Neufer, P Darrell et al. (2016) Ceramide-tamoxifen regimen targets bioenergetic elements in acute myelogenous leukemia. J Lipid Res 57:1231-42
Young, Megan M; Takahashi, Yoshinori; Fox, Todd E et al. (2016) Sphingosine Kinase 1 Cooperates with Autophagy to Maintain Endocytic Membrane Trafficking. Cell Rep 17:1532-1545
Linton, Samuel S; Sherwood, Samantha G; Drews, Kelly C et al. (2016) Targeting cancer cells in the tumor microenvironment: opportunities and challenges in combinatorial nanomedicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol 8:208-22
Olson, Kristine C; Kulling, Paige M; Olson, Thomas L et al. (2016) Vitamin D decreases STAT phosphorylation and inflammatory cytokine output in T-LGL Leukemia. Cancer Biol Ther :0
Liu, Qiang; Chen, Longgui; Atkinson, Jennifer M et al. (2016) Atg5-dependent autophagy contributes to the development of acute myeloid leukemia in an MLL-AF9-driven mouse model. Cell Death Dis 7:e2361
Aoki, Yuki; Watanabe, Takashi; Saito, Yoriko et al. (2015) Identification of CD34+ and CD34- leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia. Blood 125:967-80
Hasanali, Zainul S; Saroya, Bikramajit Singh; Stuart, August et al. (2015) Epigenetic therapy overcomes treatment resistance in T cell prolymphocytic leukemia. Sci Transl Med 7:293ra102
Morad, Samy A F; Cabot, Myles C (2015) Tamoxifen regulation of sphingolipid metabolism--Therapeutic implications. Biochim Biophys Acta 1851:1134-45
Kester, Mark; Bassler, Jocelyn; Fox, Todd E et al. (2015) Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic. Biol Chem 396:737-47

Showing the most recent 10 out of 18 publications