MacKeigan Laboratory

Selected Publications

Solitro AR, MacKeigan JP. 2016. Leaving the lysosome behind: Novel developments in autophagy inhibition. Future Med Chem 8(1):73–86.          PubMed

Klionsky DJ…MacKeigan JP…Zughaier SM. 2016. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).  Autophagy 12(1):1–222.          PubMed

Wang T, Goodall ML, Gonzales P, Sepulveda M, Martin KR, Gately S, MacKeigan JP. 2015. Synthesis of improved lysomotropic autophagy inhibitors. J Med Chem. 58(7):3025–3035.         Article

Monsma DJ, Cherba DM, Eugster EE, Dylewski D, Davidson PT, Peterson CA, Borgman AS, Winn ME, Dykema KJ, Webb CP, MacKeigan JP, Duesbery NS, Nickoloff BJ, Monks NR. 2015. Melanoma patient-derived xenografts acquire distinct vemurafenib resistance mechanisms. Am J Cancer Res 5(4):1507–1518.     PubMed

MacKeigan JP, Krueger DC. 2015. Differentiating the mTOR inhibitors everolimus and sirolimus in tuberous sclerosis complex. Neuro Oncol 17(12):1550–1559.   PubMed

Lane BR, Bissonnette J, Waldherr T, Ritz-Holland D, Chesla D, Cottingham SL, Alberta S, Liu C, Thompson AB, Graveel C, MacKeigan JP, Noyes SL, Smith J, Lakhani N, Steensma MR, Spectrum Health Tumor Sequencing Advisory Board. 2015. Development of a Center for Personalized Cancer Care at a regional cancer center: Feasibility trial of an institutional tumor sequencing advisory board. J Mol Diagn 17(6):695–704.          PubMed

Szymańska P, Martin KR, MacKeigan JP, Hlavacek WS, Lipniacki T. 2015. Computational analysis of an autophagy/translation switch based on mutual inhibition of mTORC1 and ULK1. PLOS One 10(3):e0116550.            PubMed

Burgenske DM, Monsma DJ, Dylewski D, Scott SB, Sayfie AS, Kim DG, Luchtefeld M, Martin KR, Stephenson P, Hostetter G, Dujovny N, MacKeigan JP. 2014. Establishment of genetically diverse patient-derived xenografts of colorectal cancer. Am J Cancer Res. 4(6):824–837.         PubMed

Goodall ML, Wang T, Martin KR, Kortus MG, Kauffman AL, Trent JM, Gately S, MacKeigan JP. 2014. Development of potent autophagy inhibitors that sensitize oncogenic BRAF V600E mutant melanoma tumor cells to vemurafenib. Autophagy 10(6):1120–1136.           PubMed

Westrate LM, Sayfie AD, Burgenske DM, MacKeigan JP. 2014. Persistent mitochondrial hyperfusion promotes G2/M accumulation and caspase-dependent cell death. PLoS One 9(3):e91911.             PubMed

Lanning NJ, Looyenga BD, Kauffman AL, Niemi NM, Sudderth J, DeBerardinis RJ, MacKeigan JP. 2014. A mitochondrial RNAi screen defines cellular bioenergetic determinants and identifies an adenylate kinase as a key regulator of ATP levels. Cell Rep 7(3):907–917.         PubMed

Niemi NM, Sacoman JL, Westrate LM, Gaither A, Lanning NJ, Martin KR, MacKeigan JP. 2014. The pseudophosphatase MK-STYX physically and genetically interacts with the mitochondrial phosphatase PTPMT1. PLoS One 9(4):e93896.           PubMed

Westrate LM, Drocco JA, Martin KR, Hlavacek WS, MacKeigan JP. 2014. Mitochondrial morphological features are associated with fission and fusion events. PLoS One 9(4):e95265.        PubMed

Martin KR, Narang P, Medina-Franco JL, Meurice N, MacKeigan JP. 2014. Integrating virtual and biochemical screening for protein tyrosine phosphatase inhibitor discovery. Methods 65(2):219–228.      PubMed

Gombash SE, Manfredsson FP, Kemp CJ, Kuhn NC, Fleming SM, Egan AE, Grant LM, Ciucci MR, MacKeigan JP, Sortwell C. 2013. Morphological and behavioral impact of AAV2/5-mediated overexpression of human wildtype alpha-synuclein in the rat nigrostriatal system. PLoS One 8(11):e81426.             PubMed

Looyenga BD, Resau JH, MacKeigan JP. 2013. Cytokine receptor-like factor 1 (CRLF1) protects against 6-hydroxydopamine toxicity independent of the gp130/JAK signaling pathway. PLoS One 8(6):e66548.           PubMed

Niemi NM, MacKeigan JP. 2013. Mitochondrial phosphorylation in apoptosis—flipping the death switch. Antioxid Redox Signal 19(6):572–82.          PubMed

Martin KR, Barua D, Kauffman AL, Westrate LM, Posner RG, Hlavacek WS, MacKeigan JP. 2013. Computational model for autophagic vesicle dynamics in single cells. Autophagy 9(1):74-92.            PubMed

Niemi NM, Lanning NJ, Westrate LM, MacKeigan JP. 2013. Downregulation of the mitochondrial phosphatase PTPMT1 is sufficient to promote cancer cell death. PLoS One 8(1):e53803        PubMed

Klionsky DJ et al. 2012. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8(4):445-544.        PubMed

Martin KR, Narang P, Xu Y, Kauffman AL, Petit J, Xu HE, Meurice N, MacKeigan JP. 2012. Identification of small molecule inhibitors of PTPsigma through an integrative virtual and biochemical approach. PLoS One 7(11):e50217.          PubMed

Looyenga BD, MacKeigan JP. 2012. Characterization of differential protein tethering at the plasma membrane in response to epidermal growth factor signaling. J Proteome Res 1(6):3101-3111.       PubMed

Looyenga BD, Hutchings D, Cherni I, Kingsley C, Weiss GJ, MacKeigan JP. 2012. STAT3 is activated by JAK2 independent of key oncogenic driver mutations in non-small cell lung carcinoma. PLoS One 7(2):e30820.          PubMed

Stark MS, Woods SL, Gartside MG, Bonazzi VF, Dutton-Regester K, Aoude LG, Chow D, Sereduk C, Niemi NM, Tang N, Ellis JJ, Reid J, Zismann V, Tyagi S, Muzny D, Newsham I, Wu Y, Palmer JM, Pollak T, Youngkin D, Brooks BR, Lanagan C, Schmidt CW, Kobe B, MacKeigan JP, Yin H, Brown KM, Gibbs R, Trent J, Hayward NK. 2011. Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing. Nat Genet 44(2):165–169.         PubMed

Fogg V, N Lanning, MacKeigan JP. 2011. Mitochondria in cancer: at the crossroads of life and death. Chin J Cancer 30(8): 526-539.         PubMed         Article

He Y, Xu Y, Zhang C, Gao X, Dykema KJ, Martin KR, Ke J, Hudson EA, Khoo SK, Resau JH, Alberts AS, MacKeigan JP, Furge KA, Xu HE. 2011. Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response. Sci Signal 4(180): ra44.       PubMed       Article

Ding Y, Huang D, Zhang Z, Smith J, Petillo D, Looyenga BD, Feenstra K, MacKeigan JP, Furge KA, Teh BT. 2011. Combined gene expression profiling and RNAi screening in clear cell renal cell carcinoma identify PLK1 and other therapeutic kinase targets. Cancer Res 71(51): 5225-5234.        PubMed       Article

Looyenga BD, Cherni I,  MacKeigan JP, Weiss GJ. 2011. Tailoring tyrosine kinase inhibitors to fit the lung cancer genome. Transl Oncol 4(2): 59-70.             PubMed       Article

Niemi NM, Lanning NJ, Klomp JA, Tait SW, Xu Y, Dykema KJ, Murphy LO, Gaither LA, Xu HE, Furge KA, Green DR, MacKeigan JP. 2011. MK-STYX, a catalytically inactive phosphatase regulating mitochondrial dependent apoptosis. Mol Cell Biol 31(7): 1357-1368.       PubMed        Article

Looyenga BD, Furge KA, Dykema KJ, Koeman J, Swiatek PJ, Giordano TJ, West AB, Resau JH, Teh BT, MacKeigan JP. 2011. Chromosomal amplification of leucine-rich repeat kinase-2 (LRRK2) is required for oncogenic MET signaling in papillary renal and thyroid carcinomas. Proc Natl Acad Sci USA 108(4): 1439-1444.         PubMed        Article

Martin KR, Xu Y, Looyenga BD, Davis RJ, Wu CL, Tremblay ML, Xu HE, MacKeigan JP. 2011. Identification of PTPsigma as an autophagic phosphatase. J Cell Sci 124(Pt 5):812-819.       PubMed    Article

Düvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, Vander Heiden MG, MacKeigan JP, Finan PM, Clish CB, Murphy LO, Manning BD. 2010. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell 39(2):171-183.             PubMed        Article

Furge KA, MacKeigan JP Teh BT . 2010. Kinase targets in renal cell carcinomas: reevaluating the old and discovering the new. Lancet Oncol 11(6):571-578. PubMed       Article

Klomp JA, Petillo D, Niemi NM, Dykema KJ, Chen J, Yang XJ, Sääf A, Zickert P, Aly M, Bergerheim U, Nordenskjöld M, Gad S, Giraud S, Denoux Y, Yonneau L, Méjean A, Vasiliu V, Richard S, MacKeigan JP, Teh BT, Furge KA. 2010. Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression. BMC Med Genomics 3:59.          PubMed        Article

Zhou XE, Suino-Powell KM, Li J, He Y, MacKeigan JP, Melcher K, Yong EL, Xu HE. 2010. Identification of SRC3/AIB1 as a preferred coactivator for hormone-activated androgen receptor. J Biol Chem 285(12):9161-9171.       PubMed      Article

Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, Yang H, Hild M, Kung C, Wilson C, Myer VE, MacKeigan JP, Porter JA, Wang YK, Cantley LC, Finan PM, Murphy LO. 2009. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136(3):521-534.      PubMed       Article

Elis W, Triantafellow E, Wolters NM, Sian KR, Caponigro G, Borawski J, Gaither LA, Murphy LO, Finan PM, MacKeigan JP. 2008. Down-regulation of class II phosphoinositide 3-kinase α expression below a critical threshold induces apoptotic cell death. Mol Cancer Res 6(4):614–623.        PubMed       Article

Looyenga BD, DeHaan AM, MacKeigan JP. 2008. Pink1. Nature Molecule Pages. doi:10.1038/mp.a003826.01.           Article

Wolters NM, MacKeigan JP. 2008. From sequence to function: using RNAi to elucidate mechanisms of human disease. Cell Death Differ 15(5):809-819.  PubMed       Article

Wolters NM, MacKeigan JP. 2007. Mk-styx. Nature Molecule Pages. doi:10.1038/mp.a003062.01.           Article

Dimitri CA, Dowdle W, MacKeigan JP, Blenis J, Murphy LO. 2005. Spatially separate docking sites on ERK2 regulate distinct signaling events in vivo. Curr Biol 15(14):1319–1324.         PubMed       Article

MacKeigan JP, Murphy LO, Blenis J. 2005. Graded mitogen-activated protein kinase activity precedes switch-like c-Fos induction in mammalian cells. Mol Cell Biol (11):4676–4682.        PubMed      Article

MacKeigan JP, Murphy LO, Blenis J. 2005. Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance. Nat Cell Biol 7(6):591–600.      PubMed      Article

Ballif BA, Roux PP, Gerber SA, MacKeigan JP, Blenis J, Gygi SP. 2005. Quantitative phosphorylation profiling of the ERK/p90 ribosomal S6 kinase-signaling cassette and its targets, the tuberous sclerosis tumor suppressors. Proc Natl Acad Sci USA 102(3):667–672.        PubMed       Article

Murphy LO, MacKeigan JP, Blenis J. 2004. A network of immediate early gene products propagates subtle differences in MAPK signal amplitude and duration. Mol Cell Biol 24(1):144–153.       PubMed    Article

MacKeigan JP, Clements CM, Lich JD, Pope RM, Hod Y, Ting JP. 2003. Proteomic profiling drug-induced apoptosis in non-small cell lung carcinoma: identification of RS/DJ-1 and RhoGDIalpha. Cancer Res 63(20): 6928–6934.      PubMed      Article

Taxman DJ, MacKeigan JP, Clements C, Bergstralh DT, Ting JP. 2003. Transcriptional profiling of targets for combination therapy of lung carcinoma with paclitaxel and mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor. Cancer Res 63(16):5095–5104.      PubMed      Article

MacKeigan JP, Taxman DJ, Hunter D, Earp HS, Graves LM, Ting JP. 2002. Inactivation of the antiapoptotic phosphatidylinositol 3-kinase-Akt pathway by the combined treatment of Taxol and mitogen-activated protein kinase kinase inhibition. Clin Cancer Res 8(7):2091–2099.       PubMed    Article

MacKeigan JP, Collins TS, Ting JP. 2000. MEK inhibition enhances paclitaxel-induced tumor apoptosis. J Biol Chem  275(50):38953–38956.                       PubMed      Article

Niven R, Pearlman R, Wedeking T, MacKeigan JP, Noker P, Simpson-Herren L, Smith JG. 1998. Biodistribution of radiolabeled lipid-DNA complexes and DNA in mice. J Pharm Sci 87(11):1292–1299.      PubMed      Article