Bradley R. Cairns, PhD

Title: Chair, Department of Oncological Sciences

Languages spoken: English

Academic Information

Departments: Oncological Sciences - Professor, Biochemistry - Adjunct Professor

Academic Office Information

brad.cairns@hci.utah.edu

(801) 585-1822

Huntsman Cancer Hospital
Department of Oncological Sciences
1950 Circle of Hope, Room: Rm 3725
Salt Lake City, UT 84112

Labs

Research Interests

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

Biography: Dr. Bradley 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 Ph.D. on both signal transduction and chromatin remodeling, where he was the first to purify a chromatin remodeling complex (SWI/SNF complex). He received his Ph.D. 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 Ph.D. in the Department of Genetics at Harvard Medical School (funding from the Leukemia Society of America), where he continued to study chromatin remodeling complexes, including RSC and SWI/SNF. In 1998, he joined the faculty of the Department of Oncological Sciences and the Huntsman Cancer Institute where he continues studies on chromatin remodeling mechanisms and initiated new work on germline, and early embryo chromatin and transcription mechanisms. In 2000, he was appointed as an Investigator with the Howard Hughes Medical Institute. He is now Professor and Chair of the Department of Oncological Sciences and is the Jon M. Huntsman Presidential Endowed Chair in Cancer Research, Given by the 2018 Utah State Legislature and the Chief Academic Officer at the Huntsman Cancer Institute - both within the University of Utah, School of Medicine. He was elected to the American Academy of Arts and Sciences in 2017.

Research: The Cairns lab has made many contributions to understanding chromatin structure and gene expression principles in the germline – which include: 1) The first genome-wide analyses of histone retention and modifications in human sperm, revealing the retention in mature sperm of differentially-modified histones enriched at the promoters of developmental and housekeeping genes. 2) Evidence that pluripotency network genes are silenced in spermatogonia by chromatin and DNA, and the surprising result that gametogenesis in mice and humans involves the transcription of hundreds of genes bearing DNA methylation and co-incident H3K4me3 (Hammoud et al., Cell Stem Cell, 2014). 3) The first single-cell analysis of human spermatogonia and characterization of four distinct developmental states (Guo et al., Cell Stem Cell, 2017). 4) Identification of the most undifferentiated spermatogonial state, termed State 0, and its presence from infant stages through adulthood (Guo et al., Cell Research, 2018). 4) Characterization of spermatogonia and somatic cell co-development during puberty, and exploration of roles for testosterone by examining testes from testosterone-suppressed trans females (Guo et al., Cell Stem Cell, 2020) and 5) Evidence that State 0 stem cells emerge in the fetus, and exploration of the specification of fetal somatic niche cells (Guo et al., Cell Stem Cell, 2021). Most recently, the lab collaborated to explore the impact of aging and high BMI on testis GSCs and somatic cells, revealing major alterations in somatic cell function (Nie et al., bioRxiv 2021).

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

Administration and Service: Professor and Chair of the Department of Oncological Sciences and the Chief Academic Officer at the Huntsman Cancer Institute - both within the University of Utah. 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

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

  1. Wang X, Cairns BR, Guo J (2022). When spermatogenesis meets human aging and elevated body mass. Life Med, 1(3), 267-269.
  2. Nie X, Munyoki SK, Sukhwani M, Schmid N, Missel A, Emery BR, DonorConnect, Stukenborg JB, Mayerhofer A, Orwig KE, Aston KI, Hotaling JM, Cairns BR, Guo J (2022). Single-cell analysis of human testis aging and correlation with elevated body mass index. Dev Cell, 57(9), 1160-1176.e5.
  3. Hickey GJ, Wike CL, Nie X, Guo Y, Tan M, Murphy PJ, Cairns BR (2022). Establishment of developmental gene silencing by ordered polycomb complex recruitment in early zebrafish embryos. Elife (11). England.
  4. Sun W, Guo J, McClellan D, Poeschla A, Bareyan D, Casey MJ, Cairns BR, Tantin D, Engel ME (2022). GFI1 Cooperates with IKZF1/IKAROS to Activate Gene Expression in T-cell Acute Lymphoblastic Leukemia. Mol Cancer Res, 20, 501-514.
  5. Chen H, Murray E, Sinha A, Laumas A, Li J, Lesman D, Nie X, Hotaling J, Guo J, Cairns BR, Macosko EZ, Cheng CY, Chen F (2020). Dissecting mammalian spermatogenesis using spatial transcriptomics. Cell Rep, 37(5), 109915.
  6. Grow EJ, Weaver BD, Smith CM, Guo J, Stein P, Shadle SC, Hendrickson PG, Johnson NE, Butterfield RJ, Menafra R, Kloet SL, van der Maarel SM, Williams CJ, Cairns BR (2021). p53 convergently activates Dux/DUX4 in embryonic stem cells and in facioscapulohumeral muscular dystrophy cell models. Nat Genet, 53(8), 1207-1220.
  7. Li J, Mulvihill TS, Li L, Barrott JJ, Nelson ML, Wagner L, Lock IC, Pozner A, Lambert SL, Ozenberger BB, Ward MB, Grossmann AH, Liu T, Banito A, Cairns BR, Jones KB (2021). A Role for SMARCB1 in Synovial Sarcomagenesis Reveals That SS18-SSX Induces Canonical BAF Destruction. Cancer Discov, 11(10), 2620-2637.
  8. Shi J, Zhang Y, Tan D, Zhang X, Yan M, Zhang Y, Franklin R, Shahbazi M, Mackinlay K, Liu S, Kuhle B, James ER, Zhang L, Qu Y, Zhai Q, Zhao W, Zhao L, Zhou C, Gu W, Murn J, Guo J, Carrell DT, Wang Y, Chen X, Cairns BR, Yang XL, Schimmel P, Zernicka-Goetz M, Cheloufi S, Zhang Y, Zhou T, Chen Q (2021). Author Correction: PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications. Nat Cell Biol (23(6), p. 676). England.
  9. Wike CL, Guo Y, Tan M, Nakamura R, Shaw DK, Daz N, Whittaker-Tademy AF, Durand NC, Aiden EL, Vaquerizas JM, Grunwald D, Takeda H, Cairns BR (2021). Chromatin architecture transitions from zebrafish sperm through early embryogenesis. Genome Res, 31(6), 981-994.
  10. Nakamura R, Motai Y, Kumagai M, Wike CL, Nishiyama H, Nakatani Y, Durand NC, Kondo K, Kondo T, Tsukahara T, Shimada A, Cairns BR, Aiden EL, Morishita S, Takeda H (2021). CTCF looping is established during gastrulation in medaka embryos. Genome Res, 31(6), 968-980.
  11. Guo J, Sosa E, Chitiashvili T, Nie X, Rojas EJ, Oliver E, DonorConnect, Plath K, Hotaling JM, Stukenborg JB, Clark AT, Cairns BR (2021). Single-cell analysis of the developing human testis reveals somatic niche cell specification and fetal germline stem cell establishment. Cell Stem Cell, 28(4), 764-778.e4.
  12. Shi J, Zhang Y, Tan D, Zhang X, Yan M, Zhang Y, Franklin R, Shahbazi M, Mackinlay K, Liu S, Kuhle B, James ER, Zhang L, Qu Y, Zhai Q, Zhao W, Zhao L, Zhou C, Gu W, Murn J, Guo J, Carrell DT, Wang Y, Chen X, Cairns BR, Yang XL, Schimmel P, Zernicka-Goetz M, Cheloufi S, Zhang Y, Zhou T, Chen Q (2021). PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications. Nat Cell Biol, 23(4), 424-436.
  13. DOrazio FM, Balwierz PJ, Gonzlez AJ, Guo Y, Hernndez-Rodrguez B, Wheatley L, Jasiulewicz A, Hadzhiev Y, Vaquerizas JM, Cairns B, Lenhard B, Mller F (2021). Germ cell differentiation requires Tdrd7-dependent chromatin and transcriptome reprogramming marked by germ plasm relocalization. Dev Cell, 56(5), 641-656.e5.
  14. Tharmalingam MD, Matilionyte G, Wallace WHB, Stukenborg JB, Jahnukainen K, Oliver E, Goriely A, Lane S, Guo J, Cairns B, Jorgensen A, Allen CM, Lopes F, Anderson RA, Spears N, Mitchell RT (2020). Cisplatin and carboplatin result in similar gonadotoxicity in immature human testis with implications for fertility preservation in childhood cancer. BMC Med, 18(1), 374.
  15. Clapier CR, Verma N, Parnell TJ, Cairns BR (2020). Cancer-Associated Gain-of-Function Mutations Activate a SWI/SNF-Family Regulatory Hub. Mol Cell, 80(4), 712-725.e5.
  16. Murphy PJ, Guo J, Jenkins TG, James ER, Hoidal JR, Huecksteadt T, Broberg DS, Hotaling JM, Alonso DF, Carrell DT, Cairns BR, Aston KI (2020). NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure. PLoS Genet, 16(6), e1008756.
  17. Gambini A, Stein P, Savy V, Grow EJ, Papas BN, Zhang Y, Kenan AC, Padilla-Banks E, Cairns BR, Williams CJ (2020). Developmentally Programmed Tankyrase Activity Upregulates β-Catenin and Licenses Progression of Embryonic Genome Activation. Dev Cell, 53(5), 545-560.e7.
  18. Schlichter A, Kasten MM, Parnell TJ, Cairns BR (2020). Specialization of the chromatin remodeler RSC to mobilize partially-unwrapped nucleosomes. Elife, 9.
  19. Guo J, Nie X, Giebler M, Mlcochova H, Wang Y, Grow EJ, DonorConnect, Kim R, Tharmalingam M, Matilionyte G, Lindskog C, Carrell DT, Mitchell RT, Goriely A, Hotaling JM, Cairns BR (2020). The Dynamic Transcriptional Cell Atlas of Testis Development during Human Puberty. Cell Stem Cell, 26(2), 262-276.e4.
  20. Ye Y, Wu H, Chen K, Clapier CR, Verma N, Zhang W, Deng H, Cairns BR, Gao N, Chen Z (2019). Structure of the RSC complex bound to the nucleosome. Science, 366(6467), 838-843.
  21. Rougeot J, Chrispijn ND, Aben M, Elurbe DM, Andralojc KM, Murphy PJ, Jansen PWTC, Vermeulen M, Cairns BR, Kamminga LM (2019). Maintenance of spatial gene expression by Polycomb-mediated repression after formation of a vertebrate body plan. Development, 146(19).
  22. Cakiroglu A, Clapier CR, Ehrensberger AH, Darbo E, Cairns BR, Luscombe NM, Svejstrup JQ (2019). Genome-wide reconstitution of chromatin transactions reveals that RSC preferentially disrupts H2AZ-containing nucleosomes. Genome Res, 29(6), 988-998.
  23. Guo J, Cairns BR (2019). Isolation and Enrichment of Spermatogonial Stem Cells From Human Testis Tissues. Curr Protoc Stem Cell Biol, 49(1), e77.
  24. Khoddami V, Yerra A, Mosbruger TL, Fleming AM, Burrows CJ, Cairns BR (2019). Transcriptome-wide profiling of multiple RNA modifications simultaneously at single-base resolution. Proc Natl Acad Sci U S A, 116(14), 6784-6789.
  25. Jenkins TG, Aston KI, Cairns B, Smith A, Carrell DT (2018). Paternal germ line aging: DNA methylation age prediction from human sperm. BMC Genomics, 19(1), 763.
  26. 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.
  27. 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.
  28. 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.
  29. Clapier CR, Iwasa J, Cairns BR, Peterson CL (2017). Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nat Rev Mol Cell Biol, 18(7), 407-422.
  30. Hendrickson PG, Doris 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.
  31. 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.
  32. 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.
  33. 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.
  34. Hendrickson PG, Cairns BR (2016). Tet proteins enhance the developmental hourglass. Nat Genet, 48(4), 345-7.
  35. 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.
  36. 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.
  37. 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.
  38. 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.
  39. 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.
  40. 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.
  41. Khoddami V, Yerra A, Cairns BR (2015). Experimental Approaches for Target Profiling of RNA Cytosine Methyltransferases. Methods Enzymol, 560, 273-96.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. Khoddami V, Cairns BR (2013). Identification of direct targets and modified bases of RNA cytosine methyltransferases. Nat Biotechnol, 31(5), 458-64.
  47. Clapier CR, Cairns BR (2012). Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes. Nature, 492(7428), 280-4.
  48. Oler AJ, Cairns BR (2012). PP4 dephosphorylates Maf1 to couple multiple stress conditions to RNA polymerase III repression. EMBO J, 31(6), 1440-52.
  49. 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.
  50. 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.
  51. Kasten MM, Clapier CR, Cairns BR (2011). SnapShot: Chromatin remodeling: SWI/SNF. Cell, 144(2), 310.e1.
  52. Kasten MM, Clapier CR, Cairns BR (2011). SnapShot: Chromatin remodeling: SWI/SNF. [Review]. Cell, 144(2), 310.e.l..
  53. 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.
  54. 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.
  55. Cairns BR (2009). The logic of chromatin architecture and remodelling at promoters. Nature, 461(7261), 193-8.
  56. 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.
  57. 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.
  58. 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.
  59. 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.
  60. 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.
  61. 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.
  62. 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.
  63. 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.
  64. 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.
  65. 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.
  66. Cairns BR (2004). Around the world of DNA damage INO80 days. Cell, 119(6), 733-5.