Chemistry and Biochemistry

Joshua L. Andersen

Joshua Andersen

Office: E111 BNSN
Office Phone: 801-422-7193
Lab Room: E271 BNSN
Lab Phone: 801-422-6745
Office Hours


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)


For more information about research in the Andersen Lab and living in Provo, click here: The Andersen Lab, Living in Provo.

The health of an organism is linked to the tightly regulated balance between cell proliferation and cell death. Any aberrant tilt in this balance can lead to devastating human diseases. For example, excessive proliferation unbalanced by cell death leads to cancer. On the opposite end of the spectrum, excessive cell death unbalanced by proliferation causes degenerative diseases such as Alzheimer’s, Parkinson’s and Amyotrophic Lateral Sclerosis. In the Andersen lab we use a combination of molecular and proteomics approaches to understand the mechanisms that govern this balance and how they go awry in disease. A better understanding of these processes gives us the tools to develop more targeted and effective therapies. Our recent work focuses on the following diseases/mechanisms: 

The mechanisms by which cancer cells develop resistance to therapy: Chemotherapy is the primary mode of treatment for the majority of cancers and is often the only viable treatment option. Although the initial tumor response to chemotherapy is generally positive, many tumors possess a dynamic ability to adapt and develop resistance to chemotherapy (termed “chemoresistance”), which is the most common cause of patient mortality. A major roadblock to solving this problem is our fragmented understanding of the mechanisms that cause chemoresistance in tumors. To address this problem, a central project in our lab focuses on the protein 14-3-3z, a cellular hub that orchestrates many chemoresistance-promoting mechanisms. We have approached 14-3-3 from several angles, including the direct therapeutic targeting of 14-3-3z in cancer and its use as a phospho-probe to guide us to dynamic chemoresistance mechanisms. Our recent work in this area uncovered a molecular switch that activates a cellular process called autophagy, an emerging cause of chemoresistance in a variety of cancers. In addition, we recently discovered a novel mechanism that may stabilize receptor tyrosine kinases (RTKs) to promote resistance against RTK inhibitors (e.g., lapatanib, trastuzumab, gefitinib, and others). We are currently working to understand key details of these mechanisms with the ultimate goal of developing therapeutic strategies to override tumor cell resistance to therapy.


Pathogenesis of familial Amyotrophic Lateral Sclerosis: Amyotrophic lateral sclerosis (ALS) is an aggressive neurological disease that causes the death of motor neurons, progressive paralysis, and respiratory failure. Patient lifespan typically ranges between 2-5 years from diagnosis. There is no cure for ALS nor is there a way to extend patient lifespan. Although ALS is usually a sporadic disease, roughly one-tenth of ALS cases are familial (fALS). Of these, 20% are linked to mutations in the radical-scavenging enzyme superoxide dismutase-1 (SOD1). These mutations do not uniformly affect mutant SOD1 (mutSOD1) enzymatic activity, but rather are thought to confer a toxic gain-of-function. A widely accepted model is that the gain-of-function mutations convert mutSOD1 into a toxic protein that aberrantly accumulates in mitochondria, which triggers motor neuron death. However, our poor understanding of the factors that control mutSOD1 mitochondrial accumulation has made testing this model an impossibility and has been a barrier to the development of fALS therapeutics. Toward this end, our recent work has uncovered dynamic modifications on mutSOD1 that control its accumulation in mitochondria. We are currently working to understand how these modifications are regulated and whether they can be targeted for therapeutic benefit in fALS.


  1. Mortenson JB, Heppler LN, Banks CJ, Weerasekara VK, Whited MD, Piccolo SR, Johnson WE, Thompson JW, Andersen JL. (2015) Histone Deacetylase 6 (HDAC6) modulates the pro-survival activity of 14-3-3z via deacetylation of lysines within the 14-3-3z binding pocket. Journal of Biological Chemistry. 15;290(20): 12487-96
  2. Weerasekara VK, Panek DJ, Broadbent DG, Mortenson JB, Mathis AD, Logan GN, Prince JT, Thomson DM, Thompson JW, Andersen JL. (2014) Metabolic stress-induced rearrangement of the 14-3-3z interactome promotes autophagy via a ULK1- and AMPK-regulated 14-3-3z interaction with phosphorylated Atg9A. Molecular and Cellular Biology (cover story). 34(24):4379-88
  3. 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
  4. Thompson, JW, Robeson A, Andersen JL. (2013) Biotin-switch methods to identify Sirtuin substrates. Methods Enzymology 1077:133-48
  5. Andersen JL, Kornbluth S. (2012) Untangling the metabolic and apoptotic circuitry. Molecular Cell 2;43(5): 832-842
  6. Andersen JL, Kornbluth S. (2012) Mcl-1 rescues a glitch in the matrix. Nature Cell Biology 30;14(6): 563-565
  7. 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
  8. 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)
  9. Andersen JL, and Kornbluth S. (2011) Meeting the N-terminal end with acetylation. Cell 146(4): 503-505
  10. 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
  11. Andersen JL, Kornbluth S. (2009) A cut above the other caspases. Molecular Cell 25;35(6): 733-734
  12. Nutt LK, Buchakjian MR, Gan E, Darbandi R, Sook-Young Y, Wu JQ, Miyamoto J, Gibbon JA, Andersen JL, Freel CD, Tang W, He C, Kurokawa M, Wang Y Margolis SS, Fissore RA, Kornbluth S. (2009) Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2. Developmental Cell 16(6): 856-866
  13. Andersen JL, Le Rouzic E, Planelles V. (2008) HIV-1 Vpr: Mechanisms of G2 arrest and apoptosis. Experimental and Molecular Pathology 85(1): 2-10
  14. Andersen JL, DeHart JL, Zimmerman ES, Ardon O, Kim B, Jacquot G, Benichou S, Planelles V. (2007) HIV-1 Vpr-induced apoptosis is cell cycle-dependent and requires Bax but not ANT. PLoS Pathogens 2(12): e127
  15. Dehart JL, Andersen JL, Zimmerman E, Ardon O, An DS, Blackett J, Planelles V. (2005) ATR is dispensable for retroviral integration. Journal of Virology 79(3): 1389-1396
  16. Andersen JL, Zimmerman ES, Dehart JL, Murala S, Ardon O, Blackett J, Chen J, Planelles V. (2005) ATR and Gadd45 alpha mediate HIV-1 Vpr-induced apoptosis. Cell Death and Differentiation 12(4): 326-334
  17. Andersen JL, Planelles V. (2005) The role of Vpr in HIV-1 pathogenesis. Current HIV Research 3(1): 43-51
  18. Zimmerman ES, Chen J, Andersen JL, Ardon O, Dehart JL, Blackett J, Murala S, Neghiem P, Planelles V. (2004) HIV-1 Vpr-mediated G2 arrest requires Rad17 and Hus1 and induces nuclear accumulation of BRCA1 and gamma-H2AX foci.  Molecular and Cellular Biology 24(21): 9286-9294