Donald E. Ayer, PhD

Research Interests

  • Myc
  • MondoA
  • Thioredoxin Interacting Protein
  • Transcription
  • Nutrient Sensing
  • Cancer Metabolism
  • Glycolysis
  • Glutaminolysis

Labs

Lab Website

Languages

  • English

Academic Information

  • Departments: Oncological Sciences - Professor
  • Cancer Center Programs: Nuclear Control of Cell Growth & Differentiation

Academic Office Information

  • 801-581-5597
  • Huntsman Cancer Institute
    2000 Circle of Hope, Room: 3705
    Salt Lake City, UT 84112

Academic Bio

Donald Ayer, PhD, is an investigator at Huntsman Cancer Institute (HCI) and a professor in the Department of Oncological Sciences at the University of Utah (U of U). He is a member of the Nuclear Control of Cell Growth and Differentiation Program.

Ayer is a leader in the area of gene regulation and its role in normal and cancer cell growth. His research focuses on how cells regulate a transcription factor known as Myc, which is mutated in a wide variety of cancers. In normal cells, Myc is responsible for turning on the genes that are required for cell division. In cancer cells, Myc is "hyperactive" and causes cells to divide continuously, creating excess, unnecessary cells that form a tumor. Ayer's research group investigates how Myc functions in normal and cancer cells, and they work to increase the understanding of basic gene control mechanisms. This information could greatly improve cancer diagnosis methods and treatment.

Ayer, a native of Michigan, earned a PhD in chemistry and biochemistry from the University of Colorado. From 1989 to 1995, he received additional training under the direction of Robert Eisenman, PhD, a National Academy of Science member, at the Fred Hutchinson Cancer Research Center in Seattle. In 1995, he was recruited to the U of U and HCI.

Education History

Type School Degree
Postdoctoral Fellowship Fred Hutchinson Cancer Research Center
Postdoctoral Fellow
Doctoral Training University of Colorado
Chemistry & Biochemistry
Ph.D.
Undergraduate University of Michigan
Cellular and Molecular Biology
B.S.

Selected Publications

Journal Article

  1. Schaub FX, Dhankani V, Berger AC, Trivedi M, Richardson AB, Shaw R, Zhao W, Zhang X, Ventura A, Liu Y, Ayer DE, Hurlin PJ, Cherniack AD, Eisenman RN, Bernard B, Grandori C (2018 Mar 28). Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas. Cell Syst, 6(3), 282-300.e2.
  2. Shen L, OShea JM, Kaadige MR, Cunha S, Wilde BR, Cohen AL, Welm AL, Ayer DE (2015 Apr 28). Metabolic reprogramming in triple-negative breast cancer through Myc suppression of TXNIP. Proc Natl Acad Sci U S A, 112(17), 5425-30.
  3. Carroll PA, Diolaiti D, McFerrin L, Gu H, Djukovic D, Du J, Cheng PF, Anderson S, Ulrich M, Hurley JB, Raftery D, Ayer DE, Eisenman RN (2015 Feb 9). Deregulated Myc requires MondoA/Mlx for metabolic reprogramming and tumorigenesis. Cancer Cell, 27(2), 271-85.
  4. Kaadige MR, Yang J, Wilde BR, Ayer DE (2015 Jan). MondoA-Mlx transcriptional activity is limited by mTOR-MondoA interaction. Mol Cell Biol, 35(1), 101-10.
  5. Bowman CJ, Ayer DE, Dynlacht BD (2014 Dec). Foxk proteins repress the initiation of starvation-induced atrophy and autophagy programs. Nat Cell Biol, 16(12), 1202-14.
  6. Parmenter TJ, Kleinschmidt M, Kinross KM, Bond ST, Li J, Kaadige MR, Rao A, Sheppard KE, Hugo W, Pupo GM, Pearson RB, McGee SL, Long GV, Scolyer RA, Rizos H, Lo RS, Cullinane C, Ayer DE, Ribas A, Johnstone RW, Hicks RJ, McArthur GA (2014 Apr). Response of BRAF-mutant melanoma to BRAF inhibition is mediated by a network of transcriptional regulators of glycolysis. Cancer Discov, 4(4), 423-33.
  7. OShea JM, Ayer DE (2013 Sep 1). Coordination of nutrient availability and utilization by MAX- and MLX-centered transcription networks. Cold Spring Harb Perspect Med, 3(9), a014258.
  8. Han KS, Ayer DE (2013 Jul 15). MondoA senses adenine nucleotides: transcriptional induction of thioredoxin-interacting protein. Biochem J, 453(2), 209-18.
  9. Sartor F, Jackson MJ, Squillace C, Shepherd A, Moore JP, Ayer DE, Kubis HP (2013 Apr). Adaptive metabolic response to 4 weeks of sugar-sweetened beverage consumption in healthy, lightly active individuals and chronic high glucose availability in primary human myotubes. Eur J Nutr, 52(3), 937-48.
  10. Stoltzman CA, Kaadige MR, Peterson CW, Ayer DE (2011 Nov 4). MondoA senses non-glucose sugars: regulation of thioredoxin-interacting protein (TXNIP) and the hexose transport curb. J Biol Chem, 286(44), 38027-34.
  11. Chen JL, Merl D, Peterson CW, Wu J, Liu PY, Yin H, Muoio DM, Ayer DE, West M, Chi JT (2010 Sep 2). Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA. PLoS Genet, 6(9), e1001093.
  12. Elgort MG, OShea JM, Jiang Y, Ayer DE (2010 Sep). Transcriptional and Translational Downregulation of Thioredoxin Interacting Protein Is Required for Metabolic Reprogramming during G(1). Genes Cancer, 1(9), 893-907.
  13. Kaadige MR, Elgort MG, Ayer DE (2010 Jul-Aug). Coordination of glucose and glutamine utilization by an expanded Myc network. Transcription, 1(1), 36-40.
  14. Peterson CW, Stoltzman CA, Sighinolfi MP, Han KS, Ayer DE (2010 Jun). Glucose controls nuclear accumulation, promoter binding, and transcriptional activity of the MondoA-Mlx heterodimer. Mol Cell Biol, 30(12), 2887-95.
  15. Sloan EJ, Ayer DE (2010 Jun). Myc, mondo, and metabolism. Genes Cancer, 1(6), 587-96.
  16. Kaadige MR, Looper RE, Kamalanaadhan S, Ayer DE (2009 Sep 1). Glutamine-dependent anapleurosis dictates glucose uptake and cell growth by regulating MondoA transcriptional activity. Proc Natl Acad Sci U S A, 106(35), 14878-83.
  17. Silveira AC, Hurst DR, Vaidya KS, Ayer DE, Welch DR (2009 Apr 8). Over-expression of the BRMS1 family member SUDS3 does not suppress metastasis of human cancer cells. Cancer Lett, 276(1), 32-7.
  18. Stoltzman CA, Peterson CW, Breen KT, Muoio DM, Billin AN, Ayer DE (2008 May 13). Glucose sensing by MondoA:Mlx complexes: a role for hexokinases and direct regulation of thioredoxin-interacting protein expression. Proc Natl Acad Sci U S A, 105(19), 6912-7.
  19. Pickett CL, Breen KT, Ayer DE (2007 Oct 15). A C. elegans Myc-like network cooperates with semaphorin and Wnt signaling pathways to control cell migration. Dev Biol, 310(2), 226-39.
  20. Kaadige MR, Ayer DE (2006 Sep 29). The polybasic region that follows the plant homeodomain zinc finger 1 of Pf1 is necessary and sufficient for specific phosphoinositide binding. J Biol Chem, 281(39), 28831-6.
  21. Shi X, Hong T, Walter KL, Ewalt M, Michishita E, Hung T, Carney D, Pena P, Lan F, Kaadige MR, Lacoste N, Cayrou C, Davrazou F, Saha A, Cairns BR, Ayer DE, Kutateladze TG, Shi Y, Cote J, Chua KF, Gozani O (2006 Jul 6). ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature, 442(7098), 96-9.
  22. Sans CL, Satterwhite DJ, Stoltzman CA, Breen KT, Ayer DE (2006 Jul). MondoA-Mlx heterodimers are candidate sensors of cellular energy status: mitochondrial localization and direct regulation of glycolysis. Mol Cell Biol, 26(13), 4863-71.
  23. Fleischer TC, Yun UJ, Ayer DE (2003 May). Identification and characterization of three new components of the mSin3A corepressor complex. Mol Cell Biol, 23(10), 3456-67.
  24. Eilers AL, Sundwall E, Lin M, Sullivan AA, Ayer DE (2002 Dec). A novel heterodimerization domain, CRM1, and 14-3-3 control subcellular localization of the MondoA-Mlx heterocomplex. Mol Cell Biol, 22(24), 8514-26.
  25. Yochum GS, Ayer DE (2002 Nov). Role for the mortality factors MORF4, MRGX, and MRG15 in transcriptional repression via associations with Pf1, mSin3A, and Transducin-Like Enhancer of Split. Mol Cell Biol, 22(22), 7868-76.
  26. Yochum GS, Ayer DE (2001 Jul). Pf1, a novel PHD zinc finger protein that links the TLE corepressor to the mSin3A-histone deacetylase complex. Mol Cell Biol, 21(13), 4110-8.
  27. Billin AN, Eilers AL, Coulter KL, Logan JS, Ayer DE (2000 Dec). MondoA, a novel basic helix-loop-helix-leucine zipper transcriptional activator that constitutes a positive branch of a max-like network. Mol Cell Biol, 20(23), 8845-54.
  28. Brubaker K, Cowley SM, Huang K, Loo L, Yochum GS, Ayer DE, Eisenman RN, Radhakrishnan I (2000 Nov 10). Solution structure of the interacting domains of the Mad-Sin3 complex: implications for recruitment of a chromatin-modifying complex. Cell, 103(4), 655-65.
  29. Billin AN, Thirlwell H, Ayer DE (2000 Sep). Beta-catenin-histone deacetylase interactions regulate the transition of LEF1 from a transcriptional repressor to an activator. Mol Cell Biol, 20(18), 6882-90.
  30. Billin AN, Eilers AL, Queva C, Ayer DE (1999 Dec 17). Mlx, a novel Max-like BHLHZip protein that interacts with the Max network of transcription factors. J Biol Chem, 274(51), 36344-50.
  31. Eilers AL, Billin AN, Liu J, Ayer DE (1999 Nov 12). A 13-amino acid amphipathic alpha-helix is required for the functional interaction between the transcriptional repressor Mad1 and mSin3A. J Biol Chem, 274(46), 32750-6.
  32. Laherty CD, Billin AN, Lavinsky RM, Yochum GS, Bush AC, Sun JM, Mullen TM, Davie JR, Rose DW, Glass CK, Rosenfeld MG, Ayer DE, Eisenman RN (1998 Jul). SAP30, a component of the mSin3 corepressor complex involved in N-CoR-mediated repression by specific transcription factors. Mol Cell, 2(1), 33-42.
  33. Hassig CA, Tong JK, Fleischer TC, Owa T, Grable PG, Ayer DE, Schreiber SL (1998 Mar 31). A role for histone deacetylase activity in HDAC1-mediated transcriptional repression. Proc Natl Acad Sci U S A, 95(7), 3519-24.
  34. Nagy L, Kao HY, Chakravarti D, Lin RJ, Hassig CA, Ayer DE, Schreiber SL, Evans RM (1997 May 2). Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell, 89(3), 373-80.
  35. Hassig CA, Fleischer TC, Billin AN, Schreiber SL, Ayer DE (1997 May 2). Histone deacetylase activity is required for full transcriptional repression by mSin3A. Cell, 89(3), 341-7.
  36. Ayer DE, Laherty CD, Lawrence QA, Armstrong AP, Eisenman RN (1996 Oct). Mad proteins contain a dominant transcription repression domain. Mol Cell Biol, 16(10), 5772-81.
  37. Grandori C, Mac J, Siebelt F, Ayer DE, Eisenman RN (1996 Aug 15). Myc-Max heterodimers activate a DEAD box gene and interact with multiple E box-related sites in vivo. EMBO J, 15(16), 4344-57.
  38. Kasten MM, Ayer DE, Stillman DJ (1996 Aug). SIN3-dependent transcriptional repression by interaction with the Mad1 DNA-binding protein. Mol Cell Biol, 16(8), 4215-21.
  39. Roussel MF, Ashmun RA, Sherr CJ, Eisenman RN, Ayer DE (1996 Jun). Inhibition of cell proliferation by the Mad1 transcriptional repressor. Mol Cell Biol, 16(6), 2796-801.
  40. Hurlin PJ, Foley KP, Ayer DE, Eisenman RN, Hanahan D, Arbeit JM (1995 Dec 21). Regulation of Myc and Mad during epidermal differentiation and HPV-associated tumorigenesis. Oncogene, 11(12), 2487-501.
  41. Hurlin PJ, Queva C, Koskinen PJ, Steingrimsson E, Ayer DE, Copeland NG, Jenkins NA, Eisenman RN (1995 Nov 15). Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO J, 14(22), 5646-59.
  42. Koskinen PJ, Ayer DE, Eisenman RN (1995 Jun). Repression of Myc-Ras cotransformation by Mad is mediated by multiple protein-protein interactions. Cell Growth Differ, 6(6), 623-9.
  43. Ayer DE, Lawrence QA, Eisenman RN (1995). Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell, 80(5), 767-776.
  44. Edelhoff S, Ayer DE, Zervos AS, Steingrimsson E, Jenkins NA, Copeland NG, Eisenman RN, Brent R, Disteche CM (1994 Feb). Mapping of two genes encoding members of a distinct subfamily of MAX interacting proteins: MAD to human chromosome 2 and mouse chromosome 6, and MXI1 to human chromosome 10 and mouse chromosome 19. Oncogene, 9(2), 665-8.
  45. Ayer DE, Eisenman RN (1993 Nov). A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation. Genes Dev, 7(11), 2110-9.
  46. Ayer DE, Kretzner L, Eisenman RN (1993 Jan 29). Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell, 72(2), 211-22.
  47. Ayer DE, Dynan WS (1990 Jul). A downstream-element-binding factor facilitates assembly of a functional preinitiation complex at the simian virus 40 major late promoter. Mol Cell Biol, 10(7), 3635-45.
  48. Ayer DE, Dynan WS (1988 May). Simian virus 40 major late promoter: a novel tripartite structure that includes intragenic sequences. Mol Cell Biol, 8(5), 2021-33.
  49. Ayer D, Yarus M (1986 Jan 24). The context effect does not require a fourth base pair. Science, 231(4736), 393-5.

Review

  1. Wilde BR, Ayer DE (2015 Dec 1). Interactions between Myc and MondoA transcription factors in metabolism and tumourigenesis. [Review]. Br J Cancer, 113(11), 1529-33.
  2. Peterson CW, Ayer DE (2011 Jun 1). An extended Myc network contributes to glucose homeostasis in cancer and diabetes. [Review]. Front Biosci, 16, 2206-23.
  3. Billin AN, Ayer DE (2006). The Mlx network: evidence for a parallel Max-like transcriptional network that regulates energy metabolism. [Review]. Curr Top Microbiol Immunol, 302, 255-78.
  4. Ayer DE (1999 May). Histone deacetylases: transcriptional repression with SINers and NuRDs. [Review]. Trends Cell Biol, 9(5), 193-8.
  5. Hurlin PJ, Ayer DE, Grandori C, Eisenman RN (1994). The Max transcription factor network: involvement of Mad in differentiation and an approach to identification of target genes. [Review]. Cold Spring Harb Symp Quant Biol, 59, 109-16.

Book Chapter

  1. Logan JS, Ayer DE (2002). Mad-Max. In Wiley Encyclopedia of Molecular Medicine (pp. 1995-1998). John Wiley and Sons, Inc.
  2. McArthur GA, Laherty CD, Queva C, Hurlin PJ, Loo L, James L, Grandori C, Gallant P, Shiio Y, Hokanson WC, Bush AC, Cheng PF, Lawrence QA, Pulverer B, Koskinin PJ, Foley KP, Ayer DE, Eisenman RN (1998). The Mad Protein Family Links Transcriptional Repression to Cell Differentiation. In Cold Spring Harbor Symposium (63, pp. 423-433).
  3. Ayer DE, Eisenman RN (1997). The c-Myc Protooncogene. In Molecular Biology of Cancer (pp. 419-431). San Diego, CA: Academic Press.
  4. Ayer DE, Eisenman RN (1997). The c-Myc Protooncogene. In Molecular Biology of Cancer (pp. 419-431). San Diego, CA: Academic Press.
  5. Dynan WS, Ayer DE (1987). Site specific DNA Binding Proteins Required for Transcription of the Simian Virus 40 Early and Late Promoters. In Resnikoff WS, Burgess RR, Dahlberg JE, Gross CA, Record Jr TM, Wickens MP (Eds.), RNA Polymerase and the Regulation of Transcription: a Steenbock Symposium (pp. 303-311). New York: Elsevier Science Publishing Co. Inc.

Other

  1. Hurlin PJ, Queva C, Koskinen PJ, Steingrimsson E, Ayer DE, Copeland NG, Jenkins NA, Eisenman RN (1996 Apr 15). Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO J (15(8), p. 2030). England.

Video