Bradley R. Cairns, PhD

Chair, Department of Oncological Sciences

Research Interests

  • Cancer Biology
  • Chromatin
  • Transcription Factors
  • DNA Methylation
  • Zebrafish

Labs

Lab Website

Languages

  • English

Academic Information

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

Academic Office Information

  • 801-585-1822
  • Huntsman Cancer Institute
    Department of Oncological Sciences
    2000 Circle of Hope, Room: Rm 3725
    Salt Lake City, UT 84112

Academic Bio

Biography: Dr. Cairns received his B.S. (Honors) in Chemistry from Lewis and Clark College in Portland, Oregon in 1987. He conducted his graduate work at Stanford with Nobel Laureate Roger Kornberg PhD on both signal transduction and chromatin remodeling. He received his PhD in Cell Biology from Stanford in 1996, and also conducted an early phase of postdoctoral training (funding from the American Cancer Society). Dr. Cairns received formal postdoctoral training with Fred Winston PhD in the Department of Genetics at Harvard Medical School (funding from the Leukemia Society of America), where he continued to study chromatin remodeling complexes. In 1998, he joined the faculty of the Department of Oncological Sciences and the Huntsman Cancer Institute. In 2000, he was appointed as an Investigator with the Howard Hughes Medical Institute. He is currently Professor and Chair of the Department of Oncological Sciences, and is the Jon and Karen Huntsman Presidential Professor of Cancer Research and Senior Director of Basic Science at the Huntsman Cancer Institute – both within the University of Utah, School of Medicine. He is Co-Leader of the Nuclear Control of Cell Growth and Differentiation Program. He was elected to the American Academy of Arts and Sciences in 2017.

Research: The Cairns lab strives to understand chromatin-transcription relationships – with an emphasis on development and cancer – and effectively utilizes biochemistry, genetics, and genomics in multiple model systems. The areas/questions the lab addresses include 1) Chromatin remodeling: How are nucleosomes moved and ejected by chromatin-remodeling complexes, and how is this progress misregulated in cancer? 2) Germline and embryo gene packaging: Are genes important for embryo development (and oncogenesis) packaged in special chromatin structures while in the germline and what is their fate and impact in the early embryo? 3) How is Totipotency – the ability to become any cell type – established in early cleavage-stage embryos, and are the involved factors misregulated in cancer? 4) How does the genome ‘sculpt’ chromatin structure to achieve proper gene regulation prior to the onset of transcription in embryos?

Teaching: Dr. Cairns teaches in the Gene Expression core course, and has taught many specialty chromatin course. He organizes a weekly transcription journal club and has mentored 23 PhD students.

Administration and Service: Senior Director of Basic Science, Huntsman Cancer Institute. Chairman, Department of Oncological Sciences. Co-Leader, Nuclear Control of Cell Growth and Differentiation Program, Huntsman Cancer Institute. Chair, High-Throughput Genomics Core. Chair, Bioinformatics Core. Chair, Research Informatics Core. Service: Dr. Cairns is on the editorial board of Molecular Cell and Developmental Cell, reviews grants as a standing member or ad hoc member of multiple NIH sections, and has co-organized multiple scientific meetings for Keystone, ASBMB, FASEB, and EMBL.

Research Statement

Cancer is a disease involoving improper cell growth, death and differentiation. My research focuses on determining - at the mechanistic level - how a cell normally regulates processes important to cancer such as chromatin structure, transcription, and developmental decisions.

Research: The Cairns lab strives to understand chromatin-transcription relationships – with an emphasis on development and cancer – and effectively utilizes biochemistry, genetics, and genomics in multiple model systems. The areas/questions the lab addresses include 1) Chromatin remodeling: How are nucleosomes moved and ejected by chromatin-remodeling complexes, and how is this progress misregulated in cancer? 2) Germline and embryo gene packaging: Are genes important for embryo development (and oncogenesis) packaged in special chromatin structures while in the germline and what is their fate and impact in the early embryo? 3) How is Totipotency – the ability to become any cell type – established in early cleavage-stage embryos, and are the factors involved misregulated in cancer? 4) How does the genome ‘sculpt’ chromatin structure to achieve proper gene regulation prior to the onset of transcription in embryos.

Education History

Type School Degree
Postdoctoral Fellowship Harvard Medical School - Fred Winston, PhD
Genetics
Postdoctoral Fellow
Postdoctoral Fellowship Stanford University - Roger Kornberg, PhD
Structural Biology
Postdoctoral Fellow
Doctoral Training Stanford University - Roger Kornberg, PhD
Cell Biology
Ph.D.
Undergraduate Lewis and Clark College
Chemistry (honors)
B.S.

Selected Publications

Journal Article

  1. Murphy PJ, Wu SF, James CR, Wike CL, Cairns BR (2018). Placeholder Nucleosomes Underlie Germline-to-Embryo DNA Methylation Reprogramming. Cell, 172(5), 993-1006.e13.
  2. Hendrickson PG, Dorais JA, Grow EJ, Whiddon JL, Lim JW, Wike CL, Weaver BD, Pflueger C, Emery BR, Wilcox AL, Nix DA, Peterson CM, Tapscott SJ, Carrell DT, Cairns BR (2017). Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons. Nat Genet, 49(6), 925-934.
  3. Jenkins TG, James ER, Alonso DF, Hoidal JR, Murphy PJ, Hotaling JM, Cairns BR, Carrell DT, Aston KI (2017). Cigarette smoking significantly alters sperm DNA methylation patterns. Andrology, 5(6), 1089-1099.
  4. Guo J, Grow EJ, Yi C, Mlcochova H, Maher GJ, Lindskog C, Murphy PJ, Wike CL, Carrell DT, Goriely A, Hotaling JM, Cairns BR (2017). Chromatin and Single-Cell RNA-Seq Profiling Reveal Dynamic Signaling and Metabolic Transitions during Human Spermatogonial Stem Cell Development. Cell Stem Cell, 21(4), 533-546.e6.
  5. Clapier CR, Kasten MM, Parnell TJ, Viswanathan R, Szerlong H, Sirinakis G, Zhang Y, Cairns BR (2016). Regulation of DNA Translocation Efficiency within the Chromatin Remodeler RSC/Sth1 Potentiates Nucleosome Sliding and Ejection. Mol Cell, 62(3), 453-461.
  6. Ramakrishnan S, Pokhrel S, Palani S, Pflueger C, Parnell TJ, Cairns BR, Bhaskara S, Chandrasekharan MB (2016). Counteracting H3K4 methylation modulators Set1 and Jhd2 co-regulate chromatin dynamics and gene transcription. Nat Commun, 7, 11949.
  7. Jones KB, Barrott JJ, Xie M, Haldar M, Jin H, Zhu JF, Monument MJ, Mosbruger TL, Langer EM, Randall RL, Wilson RK, Cairns BR, Ding L, Capecchi MR (2016). The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis. Oncogene, 35(38), 5021-32.
  8. Hendrickson PG, Cairns BR (2016). Tet proteins enhance the developmental hourglass. Nat Genet, 48(4), 345-7.
  9. Varshney D, Vavrova-Anderson J, Oler AJ, Cowling VH, Cairns BR, White RJ (2015). SINE transcription by RNA polymerase III is suppressed by histone methylation but not by DNA methylation. Nat Commun, 6, 6569.
  10. Parnell TJ, Schlichter A, Wilson BG, Cairns BR (2015). The chromatin remodelers RSC and ISW1 display functional and chromatin-based promoter antagonism. Elife, 4, e06073.
  11. Khoddami V, Yerra A, Cairns BR (2015). Experimental Approaches for Target Profiling of RNA Cytosine Methyltransferases. Methods Enzymol, 560, 273-96.
  12. Aston KI, Uren PJ, Jenkins TG, Horsager A, Cairns BR, Smith AD, Carrell DT (2015). Aberrant sperm DNA methylation predicts male fertility status and embryo quality. Fertil Steril, 104(6), 1388-97.e1-5.
  13. Huang F, Ramakrishnan S, Pokhrel S, Pflueger C, Parnell TJ, Kasten MM, Currie SL, Bhachech N, Horikoshi M, Graves BJ, Cairns BR, Bhaskara S, Chandrasekharan MB (2015). Interaction of the Jhd2 Histone H3 Lys-4 Demethylase with Chromatin Is Controlled by Histone H2A Surfaces and Restricted by H2B Ubiquitination. J Biol Chem, 290(48), 28760-77.
  14. Hammoud SS, Low DH, Yi C, Lee CL, Oatley JM, Payne CJ, Carrell DT, Guccione E, Cairns BR (2015). Transcription and imprinting dynamics in developing postnatal male germline stem cells. Genes Dev, 29(21), 2312-24.
  15. Parnell T J, Schlicter A, Wilson B G, Cairns B R (Spring 2015). The chromatin remodelers RSC and ISW1 display functional and chromatin-based promoter antagonism. eLife, 4, e06073.
  16. Jenkins TG, Aston KI, Pflueger C, Cairns BR, Carrell DT (2014). Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility. PLoS Genet, 10(7), e1004458.
  17. Hammoud SS, Low DH, Yi C, Carrell DT, Guccione E, Cairns BR (2014). Chromatin and transcription transitions of mammalian adult germline stem cells and spermatogenesis. Cell Stem Cell, 15(2), 239-53.
  18. Nelson AC, Cauceglia JW, Merkley SD, Youngson NA, Oler AJ, Nelson RJ, Cairns BR, Whitelaw E, Potts WK (2013). Reintroducing domesticated wild mice to sociality induces adaptive transgenerational effects on MUP expression. Proc Natl Acad Sci U S A, 110(49), 19848-53.
  19. Khoddami V, Cairns BR (2013). Identification of direct targets and modified bases of RNA cytosine methyltransferases. Nat Biotechnol, 31(5), 458-64.
  20. Potok ME, Nix DA, Parnell TJ, Cairns BR (2013). Reprogramming the maternal zebrafish genome after fertilization to match the paternal methylation pattern. Cell, 153(4), 759-72.
  21. Oler AJ, Cairns BR (2012). PP4 dephosphorylates Maf1 to couple multiple stress conditions to RNA polymerase III repression. EMBO J, 31(6), 1440-52.
  22. Clapier CR, Cairns BR (2012). Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes. Nature, 492(7428), 280-4.
  23. Wu SF, Zhang H, Cairns BR (2011). Genes for embryo development are packaged in blocks of multivalent chromatin in zebrafish sperm. Genome Res, 21(4), 578-89.
  24. Sirinakis G, Clapier CR, Gao Y, Viswanathan R, Cairns BR, Zhang Y (2011). The RSC chromatin remodelling ATPase translocates DNA with high force and small step size. EMBO J, 30(12), 2364-72.
  25. Oler AJ, Alla RK, Roberts DN, Wong A, Hollenhorst PC, Chandler KJ, Cassiday PA, Nelson CA, Hagedorn CH, Graves BJ, Cairns BR (2010). Human RNA polymerase III transcriptomes and relationships to Pol II promoter chromatin and enhancer-binding factors. Nat Struct Mol Biol, 17(5), 620-8.
  26. Rai K, Sarkar S, Broadbent TJ, Voas M, Grossmann KF, Nadauld LD, Dehghanizadeh S, Hagos FT, Li Y, Toth RK, Chidester S, Bahr TM, Johnson WE, Sklow B, Burt R, Cairns BR, Jones DA (2010). DNA demethylase activity maintains intestinal cells in an undifferentiated state following loss of APC. Cell, 142(6), 930-42.
  27. Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR (2009). Distinctive chromatin in human sperm packages genes for embryo development. Nature, 460(7254), 473-8.
  28. Rai K, Huggins IJ, James SR, Karpf AR, Jones DA, Cairns BR (2008). DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell, 135(7), 1201-12.
  29. Dutrow N, Nix DA, Holt D, Milash B, Dalley B, Westbroek E, Parnell TJ, Cairns BR (2008). Dynamic transcriptome of Schizosaccharomyces pombe shown by RNA-DNA hybrid mapping. Nat Genet, 40(8), 977-86.
  30. Szerlong H, Hinata K, Viswanathan R, Erdjument-Bromage H, Tempst P, Cairns BR (2008). The HSA domain binds nuclear actin-related proteins to regulate chromatin-remodeling ATPases. Nat Struct Mol Biol, 15(5), 469-76.
  31. VanDemark AP, Kasten MM, Ferris E, Heroux A, Hill CP, Cairns BR (2007). Autoregulation of the rsc4 tandem bromodomain by gcn5 acetylation. Mol Cell, 27(5), 817-28.
  32. Rai K, Chidester S, Zavala CV, Manos EJ, James SR, Karpf AR, Jones DA, Cairns BR (2007). Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish. Genes Dev, 21(3), 261-6.
  33. Roberts DN, Wilson B, Huff JT, Stewart AJ, Cairns BR (2006). Dephosphorylation and genome-wide association of Maf1 with Pol III-transcribed genes during repression. Mol Cell, 22(5), 633-44.
  34. Soutourina J, Bordas-Le Floch V, Gendrel G, Flores A, Ducrot C, Dumay-Odelot H, Soularue P, Navarro F, Cairns BR, Lefebvre O, Werner M (2006). Rsc4 connects the chromatin remodeler RSC to RNA polymerases. Mol Cell Biol, 26(13), 4920-33.
  35. Zhang H, Roberts DN, Cairns BR (2005). Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell, 123(2), 219-31.
  36. Saha A, Wittmeyer J, Cairns BR (2005). Chromatin remodeling through directional DNA translocation from an internal nucleosomal site. Nat Struct Mol Biol, 12(9), 747-55.

Review

  1. Clapier CR, Iwasa J, Cairns BR, Peterson CL (2017). Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. [Review]. Nat Rev Mol Cell Biol, 18(7), 407-422.
  2. Kasten MM, Clapier CR, Cairns BR (2011). SnapShot: Chromatin remodeling: SWI/SNF. [Review]. Cell, 144(2), 310.e.l..
  3. Cairns BR (2009). The logic of chromatin architecture and remodelling at promoters. [Review]. Nature, 461(7261), 193-8.