Edinger, Aimee - University of California, Irvine - Department of Developmental and Cell Biology

研究领域

My lab is investigating the hypothesis that mammalian cell growth is regulated at the level of nutrient transporter expression. Although the bloodstream constantly supplies mammalian cells with nutrients, signal transduction cascades regulate access to these nutrients by modulating the expression of nutrient transport systems in the cell membrane. By identifying the proteins regulating nutrient transporter expression and trafficking, we expect to gain insight into normal cell biology and identify novel therapeutic targets in cancer. Normal cells become quiescent when restricted for nutrients. Cancer cells, on the other hand, have activated oncogenes that promote growth regardless of the extracellular conditions and deleted the tumor suppressor proteins that allow them to switch to catabolism. Thus, drugs that limit nutrient transporter expression are likely to be selectively toxic to tumor cells. In order to pursue this idea, my lab has amassed expertise and reagents that allow us to examine how alterations in bioenergetics characteristic of cancer cells interact with conditions that alter nutrient transporter expression. One area of particular interest is autophagy—the adaptive cellular response to the starvation induced by nutrient transporter loss. Through autophagy, (literally, eating one’s self) cells recycle their constituents to provide essential nutrients. We have shown that cells undergoing autophagy in the presence of abundant extracellular nutrients are often cells that have reduced nutrient transporter expression. We have also found that blocking apoptosis (programmed cell death) does not stop nutrient transporter loss from killing cells. The ability of nutrient transporter down-regulation to kill cells necrotically could be useful in cancer therapy as most tumor cells have disabled apoptotic pathways. These studies are also highly relevant to the fields of diabetes and aging.

近期论文

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Fransson R*, McCracken AN*, Chen B, McMonigle RJ, Edinger AL# and S Hanessian#. Design, Synthesis, and Anti-leukemic Activity of Stereochemically Defined Constrained Analogs of FTY720 (Gilenya). ACS Medicinal Chemistry Letters, in press. (* = co-first authors, # = co-corresponding authors) Guenther GG*, Liu G*, Ramirez MU, McMonigle RJ, McCracken AN, Kim SM, Joo Y, Ushach I, Nguyen NL, and AL Edinger (2013). Loss of TSC2 confers resistance to ceramide and nutrient deprivation. Oncogene (ePub ahead of print). Roy SG, Stevens MW, So L and AL Edinger (2013). Reciprocal effects of Rab7 deletion in activated and neglected T cells. Autophagy vol. 9, issue 7 (ePub ahead of print). McCracken AN and AL Edinger (2013). Nutrient transporters: the Achilles’ heel of anabolism. Trends in Endocrinology and Metabolism 24:200-8. Klionsky DJ . . . Edinger AL . . . (and others) (2012). Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 8:445-544. Chen J, Narayan S, Edinger AL, and MJ Bennett (2012). Flow injection tandem mass spectrometric measurement of ceramides of multiple chain lengths in biological samples. J Chromatogr B Analyt Technol Biomed Life Sci. 883-884: 136-140. Romero Rosales K, Singh G, Wu K, Chen J, Lilly MB, Peralta ER, Janes MR, Siskind LJ, Bennett MJ, Fruman DA, and AL Edinger (2011). Sphingolipid-based drugs selectively kill cancer cells by down-regulating nutrient transporter proteins. Biochem. J. 439:299-311. AL Edinger (2011). Unequal in the absence of death: A novel screen identifies cytotoxic compounds selective for cells with activated Akt. Cancer Biol Ther. 10:1262-5. Walsh CM and AL Edinger (2010). The complex interplay between autophagy, apoptosis, and necrotic signals promotes T-cell homeostasis. Immunol. Rev. 236:95-109. Peralta EP, Martin BC, and AL Edinger (2010). TBC1D15 is a selective Rab7 GTPase activating protein but mammalian Vps39 does not modulate Rab7 GTP binding status. J. Biol. Chem. 285:16814-21.http://www.ncbi.nlm.nih.gov/pubmed/20363736 This paper identifies proteins that regulate lysosomal dynamics and shows that they modulate growth factor dependence.