个人简介

BS, Brigham Young University (1997-2001) Ph.D., University of Utah (2001-2006) NIH and American Cancer Society Fellow, Duke University (2006-2011) Assistant Professor of Medicine, Duke University (2011-2012)

研究领域

Biochemistry

Apoptosis, a form of programmed cell death, plays a vital role in maintaining tissue homeostasis during development and in adult organisms. Indeed, tissue homeostasis is maintained by a strict balance of cell proliferation and apoptosis, and any aberrant tilt in this balance can lead to human disease. For example, excessive apoptosis, unbalanced by proliferation, underlies the etiology of neurodegenerative diseases (e.g., Alzheimer’s disease). At the other end of the spectrum, excessive cell proliferation and defective apoptotic signaling lead to cancer. Nearly half of us will be afflicted with cancer in our lifetime and for the majority of patients, cytotoxic chemotherapy is the primary treatment option. The goal of these treatments is to induce tumor cell death. However, these therapies are often ineffective because tumor cells possess the dynamic ability to subvert cell death and become chemoresistant. With this in mind, our research combines molecular and proteomics approaches to understand the mechanisms by which tumor cells gain resistance to cell death and chemotherapy, with the ultimate goal of developing therapeutic approaches to overcome chemoresistance and improve clinical outcomes for patients. How do tumor cells adapt metabolically to their environment and what effect does this adaptation have on chemosensitivity? This key question is the basis for the current projects in the Andersen lab, and is particularly important in the context of tumor hypoxia (low oxygen levels). Most solid tumors possess regions of hypoxia in which cancerous cells face one of two options: Either adapt metabolically to survive or die. Unfortunately, some tumor cells adapt and, through a process that is poorly understood, become chemoresistant. We are interested in defining the mechanisms by which this chemoresistance develops, with particular focus on the role of lysine acetylation-- a widespread but enigmatic protein modification thought to play a key role in tuning a cell’s metabolism to the available nutrient supply. We posit that changes in lysine acetylation play an integral part in metabolic adaptation to hypoxia, and modulate apoptotic-signaling pathways. We are exploring this idea on the “macro” level, using proteomics tools to assess changes in acetylation across the proteome in response to hypoxia and other metabolic stresses; and on the “micro” level, examining the impact of these changes in acetylation on the function of specific proteins that regulate cell death. Additionally, we are using several discovery platforms to identify metabolic and acetylation-regulating proteins with roles in modulating a tumor cell’s ability to adapt and survive under conditions of metabolic stress.

近期论文

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Weerasekara VK, Panek DJ, Broadbent DG, Mortenson JB, Mathis AD, Logan GN, Prince JT, Thomson DM, Andersen JL. Metabolic stress-induced rearrangement of the 14-3-3z interactome promotes autophagy via a ULK1-and AMPK-regulated 14-3-3z interaction with phosphorylated Atg9. Molecular and Cellular Biology. Epub ahead of print. Johnson SE, Lindblom KR, Robeson A, Stevens RD, Ilkayeva OR, Newgard CB, Kornbluth S, Andersen JL. (2013) Metabolomics profiling reveals a role for caspase-2 in lipoapoptosis. Journal of Biological Chemistry 17;288(20):14463-75 Thompson JW, *Robeson A, Andersen JL. (2013) Biotin-switch methods to identify enzyme substrates. Methods in Molecular Biology 1077:133-48 Andersen JL, Kornbluth S. (2012) "The tangled circuitry of metabolism and apoptosis" Molecular Cell 7;49(3):399-410 Andersen JL, Kornbluth S. (2012) "Mcl-1 rescues a glitch in the matrix." Nature Cell Biology 30;14(6): 563-565 Parrish AB, Kim J, Kurokawa M, Matsuura K, Freel CD, Andersen JL, Johnson CE, Kornbluth S. (2012) "RSK mediated phosphorylation and 14-3-3e binding of Apaf-1 suppresses cytochrome c-induced apoptosis." EMBO J. 31(5): 1279-1292 Andersen JL, Thompson JW, Lindblom KR, Johnson ES, Yang CS, Lilley LR, Freel CD, Mosely MA, Kornbluth S. (2011) "A biotin switch-based proteomics approach identifies 14-3-3z as a target of sirt1 in the metabolic regulation of caspase-2." Molecular Cell 43(5): 834-842 (cover story) Andersen JL, and Kornbluth S. (2011) "Meeting the N-terminal end with acetylation." Cell 146(4):503-505 Andersen JL, Johnson CE, Freel CD, Parrish AB, Day JL, Buchakjian MR, Nutt LK, Thompson JW, Moseley MA, Kornbluth S. (2009) "Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2." EMBO J. 28(20): 3216-3227 Andersen JL, Kornbluth S. (2009) "A cut above the other caspases." Molecular Cell 25;35(6):733-734