An important objective of the POl application is to define the contribution of altered sphingolipid metabolism in Acute Myeloid Leukemia (AML). Through the multiple Projects, the roles of specific sphingolipids and sphingolipid enzymes in AML and the efficacy of therapeutically targeting sphingolipid metabolism for AML will be defined. In order to achieve these objectives the Targeted Sphing"omics" Core will provide critical information to the Projects through two objectives;1) The Core will quantify changes in the sphingolipidome (lipids and proteins), identifying new therapeutic targets for AML, and testing the efficacy of sphingolipid-based therapeutics and 2) the Core will provide standardized measurements of sphingolipids and their metabolizing enzymes for all four Projects. These objectives will create new hypotheses into the roles of sphingolipids in AML and serves to assist the Projects in testing their specific hypotheses. Taken together, this will lead to an understanding of the contributions of, and therapeutic efficacy of, targeting sphingolipid metabolism.

Public Health Relevance

Acute Myeloid Leukemia (AML) is the most common acute leukemia affecting adults. The complexity of AML is attributed to multiple subtypes based on cyto- and molecular-genetics. This Core serves a role in hypothesis generation for the Projects by seeking to understand alterations in sphingolipid and glycosphingolipid metabolism within different subsets of patients with AML and hypothesis testing by providing standardized measurements of the sphingolipid pathways. The outcome of these studies will help validate and define new sphingolipid-based therapeutic targets for AML.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01CA171983-02
Application #
8757118
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
DUNS #
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

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