Robert C Dickson

Bio / Education: 

B.S. University of Redlands
Ph.D. University of California, Los Angeles

Research Description: 

Some people grow old yet show few signs of aging, while others show signs of aging long before they grow old. How can this be? We are trying to identify and understand the signal transduction pathways and cellular processes that control the rate of biological aging and lifespan. We use the common baker’s yeast Saccharomyces cerevisiae as a model eukaryote because it has a short lifespan that can be analyzed by genetic and biochemical techniques. Furthermore, the first gene that regulates lifespan was identified in this organism and it continues to yield new insights into the molecular mechanisms of aging. A striking outcome of studies in model organisms is that similar proteins and signaling pathways regulate lifespan. Glucose in yeast and insulin or insulin-like growth factor in other organisms regulates a signal transduction pathway that limits or down-regulates lifespan, shown experimentally by deleting a component of the pathway and seeing an increase in lifespan. Protein kinases are a well-conserved feature of these signaling pathways. The Akt/PKB protein kinases are found in organisms ranging from baker’s yeast, where the protein is called Sch9, to worms and man where these kinases play roles in insulin signaling, apoptosis and cell proliferation, all of which play roles in aging and lifespan.

One focus of research in my laboratory is the Sch9 protein kinase that regulates lifespan as measured by how many times a cell can divide (Replicative lifespan) and by how long a cell can survive in stationary phase after it stops dividing (Chronological lifespan). To understand how Sch9 regulates lifespan we are examining how nutrients (such as glucose) control production of the sphingolipid called PHS (phytosphingosine), and how PHS turns on the kinase activity of the Pkh1 protein kinase that is needed to activate Sch9 kinase activity. In addition, nutrients control another protein kinase called TORC1 (Target of Rapamycin Complex 1) that is also needed to turn on Sch9 kinase activity. We are also trying to identify proteins that are phosphorylated by Sch9. Once these substrate proteins are identified we determine if they play roles in lifespan, and if they do, we determine the molecular mechanism by which they regulate lifespan. Since there is conservation of function between yeast and mammals, the insight gained from these studies will advance our knowledge of normal cellular functions involved in aging and longevity and abnormal states including cancers, cardiovascular disease and neurological disorders.

PubMed Publications: 

  • Neimanis, I.;Gaebel, K.;Dickson, R.C.;Levy, R.;Goebel, C.;Zizzo, A.J.;Woods, A.;Corsini, J. "Committee on Utilization, Review, and Education common referral form." Canadian family physician Medecin de famille canadien 60, 10 (2014): 916. [PubMed Link] | [ Full text ]
  • Huang, X.;Withers, B.R.;Dickson, R.C. "Sphingolipids and lifespan regulation." Biochimica et biophysica acta 1841, 5 (2014): 657-64. [PubMed Link] | [ Full text ]
  • Liu, J.;Huang, X.;Withers, B.R.;Blalock, E.;Liu, K.;Dickson, R.C. "Reducing sphingolipid synthesis orchestrates global changes to extend yeast lifespan." Aging cell 12, 5 (2013): 833-41. [PubMed Link] | [ Full text ]
  • Dickson, R.C. "Not all diclofenac is equal." CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 185, 8 (2013): 687. [PubMed Link] | [ Full text ]
  • Huang, X.;Liu, J.;Withers, B.R.;Samide, A.J.;Leggas, M.;Dickson, R.C. "Reducing signs of aging and increasing lifespan by drug synergy." Aging cell 12, 4 (2013): 652-60. [PubMed Link] | [ Full text ]
  • Lester, R.L.;Withers, B.R.;Schultz, M.A.;Dickson, R.C. "Iron, glucose and intrinsic factors alter sphingolipid composition as yeast cells enter stationary phase." Biochimica et biophysica acta 1831, 4 (2013): 726-36. [PubMed Link] | [ Full text ]
  • Aguilar Madrid, G.;Beaudry, M.;Bell, W.;Bowes, D.;Brophy, J.;Burdorf, A.;Carlsten, C.;Castleman, B.;Chaturvedi, S.;Conti, M.E.;Corra, L.;Corrêa Filho, H.R.;Cranor, C.F.;Cullen, E.;Dalvie, A.;Dickson, R.C.;Digon, A.;Egilman, D.;Eisner Falvo, C.;Fischer, E.;Frank, A.L.;Frank, E.;Gee, D.;Giannasi, F.;Goldstein, B.D.;Greenberg, M.;Guidotti, T.L.;Harris, W.A.;Hindry, M.;Houlson, A.;Hu, H.;Huff, J.;Infante, P.F.;Thambyappa, J.;Juarez Perez, C.A.;Jeebhay, M.F.;Joshi, T.K.;Keith, M.;Keyserlingk, J.R.;Khatter, K.;King, D.;Kodeih, N.;Kristensen, J.;Kulsomboon, V.;Landrigan, P.J.;Lee, C.W.;Leigh, J.;Lemen, R.A.;Lippman, A.;London, L.;Matzopoulos, R.;McCulloch, J.;McDiarmid, M.A.;Mehrdad, R.;Mirabelli, D.;Moshammer, H.;Notebaert, É.;Nycz, Z.;Oberta, A.F.;O'Connor, J.;O'Neill, R.;Orris, P.;Ozonoff, D.;Paek, D.;Rickard, C.;Rodriguez, E.J.;Sass, J.;Sentes, K.E.;Simpson, I.M.;Soffritti, M.;Soskolne, C.L.;Sparling, S.P.;Spiegel, J.;Takahashi, K.;Takaro, T.K.;Terracini, B.;Thébaud-Mony, A.;Trosic, I.;Turcotte, F.;Vakil, C.;Van Der Walt, A.;Waterman, Y.R.;Watterson, A.;Wegman, D.H.;Welch, L.S.;Weiss, S.H.;Winston, R.;Yassi, A. "Statement in response to asbestos industry efforts to prevent a ban on asbestos in Pakistan: chrysotile asbestos use is not safe and must be banned." Archives of environmental & occupational health 68, 4 (2013): 243-9. [PubMed Link] | [ Full text ]
  • Lee, Y.J.;Huang, X.;Kropat, J.;Henras, A.;Merchant, S.S.;Dickson, R.C.;Chanfreau, G.F. "Sphingolipid signaling mediates iron toxicity." Cell metabolism 16, 1 (2012): 90-6. [PubMed Link] |
  • Huang, X.;Liu, J.;Dickson, R.C. "Down-regulating sphingolipid synthesis increases yeast lifespan." PLoS genetics 8, 2 (2012): e1002493. [PubMed Link] | [ Full text ]
  • Luo, G.;Costanzo, M.;Boone, C.;Dickson, R.C. "Nutrients and the Pkh1/2 and Pkc1 protein kinases control mRNA decay and P-body assembly in yeast." The Journal of biological chemistry 286, 11 (2011): 8759-70. [PubMed Link] | [ Full text ]
  • Dickson, R.C. "Roles for sphingolipids in Saccharomyces cerevisiae." Advances in experimental medicine and biology 688, (2010): 217-31. [PubMed Link] |
  • Dickson, R.C. "Thematic review series: sphingolipids. New insights into sphingolipid metabolism and function in budding yeast." Journal of lipid research 49, 5 (2008): 909-21. [PubMed Link] | [ Full text ]
  • Dickson, R.C. "More chores for TOR: de novo ceramide synthesis." Cell metabolism 7, 2 (2008): 99-100. [PubMed Link] |
  • Luo, G.;Gruhler, A.;Liu, Y.;Jensen, O.N.;Dickson, R.C. "The sphingolipid long-chain base-Pkh1/2-Ypk1/2 signaling pathway regulates eisosome assembly and turnover." The Journal of biological chemistry 283, 16 (2008): 10433-44. [PubMed Link] | [ Full text ]
  • Brace, J.L.;Lester, R.L.;Dickson, R.C.;Rudin, C.M. "SVF1 regulates cell survival by affecting sphingolipid metabolism in Saccharomyces cerevisiae." Genetics 175, 1 (2007): 65-76. [PubMed Link] | [ Full text ]
  • Dickson, R.C.;Sumanasekera, C.;Lester, R.L. "Functions and metabolism of sphingolipids in Saccharomyces cerevisiae." Progress in lipid research 45, 6 (2006): 447-65. [PubMed Link] | [ Full text ]
  • Valachovic, M.;Bareither, B.M.;Shah Alam Bhuiyan, M.;Eckstein, J.;Barbuch, R.;Balderes, D.;Wilcox, L.;Sturley, S.L.;Dickson, R.C.;Bard, M. "Cumulative mutations affecting sterol biosynthesis in the yeast Saccharomyces cerevisiae result in synthetic lethality that is suppressed by alterations in sphingolipid profiles." Genetics 173, 4 (2006): 1893-908. [PubMed Link] | [ Full text ]
  • Liu, K.;Zhang, X.;Sumanasekera, C.;Lester, R.L.;Dickson, R.C. "Signalling functions for sphingolipid long-chain bases in Saccharomyces cerevisiae." Biochemical Society transactions 33, Pt 5 (2005): 1170-3. [PubMed Link] | [ Full text ]
  • Zink, S.;Mehlgarten, C.;Kitamoto, H.K.;Nagase, J.;Jablonowski, D.;Dickson, R.C.;Stark, M.J.;Schaffrath, R. "Mannosyl-diinositolphospho-ceramide, the major yeast plasma membrane sphingolipid, governs toxicity of Kluyveromyces lactis zymocin." Eukaryotic cell 4, 5 (2005): 879-89. [PubMed Link] | [ Full text ]
  • Liu, K.;Zhang, X.;Lester, R.L.;Dickson, R.C. "The sphingoid long chain base phytosphingosine activates AGC-type protein kinases in Saccharomyces cerevisiae including Ypk1, Ypk2, and Sch9." The Journal of biological chemistry 280, 24 (2005): 22679-87. [PubMed Link] | [ Full text ]
  • Zhang, X.;Lester, R.L.;Dickson, R.C. "Pil1p and Lsp1p negatively regulate the 3-phosphoinositide-dependent protein kinase-like kinase Pkh1p and downstream signaling pathways Pkc1p and Ypk1p." The Journal of biological chemistry 279, 21 (2004): 22030-8. [PubMed Link] | [ Full text ]
  • Hearn, J.D.;Lester, R.L.;Dickson, R.C. "The uracil transporter Fur4p associates with lipid rafts." The Journal of biological chemistry 278, 6 (2003): 3679-86. [PubMed Link] | [ Full text ]
  • Chung, J.H.;Lester, R.L.;Dickson, R.C. "Sphingolipid requirement for generation of a functional v1 component of the vacuolar ATPase." The Journal of biological chemistry 278, 31 (2003): 28872-81. [PubMed Link] | [ Full text ]
  • Ferguson-Yankey, S.R.;Skrzypek, M.S.;Lester, R.L.;Dickson, R.C. "Mutant analysis reveals complex regulation of sphingolipid long chain base phosphates and long chain bases during heat stress in yeast." Yeast (Chichester, England) 19, 7 (2002): 573-86. [PubMed Link] | [ Full text ]
  • Dickson, R.C.;Lester, R.L. "Sphingolipid functions in Saccharomyces cerevisiae." Biochimica et biophysica acta 1583, 1 (2002): 13-25. [PubMed Link] | [ Full text ]
  • Hait, N.C.;Fujita, K.;Lester, R.L.;Dickson, R.C. "Lcb4p sphingoid base kinase localizes to the Golgi and late endosomes." FEBS letters 532, 1-2 (2002): 97-102. [PubMed Link] |
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