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.
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.
|Shaw, Jeremy; Costa-Pinheiro, Pedro; Patterson, Logan et al. (2018) Novel Sphingolipid-Based Cancer Therapeutics in the Personalized Medicine Era. Adv Cancer Res 140:327-366|
|Zhang, Xuewei; Kitatani, Kazuyuki; Toyoshima, Masafumi et al. (2018) Ceramide Nanoliposomes as a MLKL-Dependent, Necroptosis-Inducing, Chemotherapeutic Reagent in Ovarian Cancer. Mol Cancer Ther 17:50-59|
|Verma, Mohit K; Clemens, Julia; Burzenski, Lisa et al. (2017) A novel hemolytic complement-sufficient NSG mouse model supports studies of complement-mediated antitumor activity in vivo. J Immunol Methods 446:47-53|
|Olson, Kristine C; Kulling, Paige M; Olson, Thomas L et al. (2017) Vitamin D decreases STAT phosphorylation and inflammatory cytokine output in T-LGL leukemia. Cancer Biol Ther 18:290-303|
|Hengst, Jeremy A; Dick, Taryn E; Sharma, Arati et al. (2017) SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models. Cancer Transl Med 3:109-121|
|Morad, Samy A F; Davis, Traci S; MacDougall, Matthew R et al. (2017) Role of P-glycoprotein inhibitors in ceramide-based therapeutics for treatment of cancer. Biochem Pharmacol 130:21-33|
|Doshi, Ushma A; Shaw, Jeremy; Fox, Todd E et al. (2017) STAT3 mediates C6-ceramide-induced cell death in chronic lymphocytic leukemia. Signal Transduct Target Ther 2:17051|
|Tan, Su-Fern; Pearson, Jennifer M; Feith, David J et al. (2017) The emergence of acid ceramidase as a therapeutic target for acute myeloid leukemia. Expert Opin Ther Targets 21:583-590|
|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|
|Tan, Su-Fern; Liu, Xin; Fox, Todd E et al. (2016) Acid ceramidase is upregulated in AML and represents a novel therapeutic target. Oncotarget 7:83208-83222|
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