Peter Jones
Laboratory

Epigenetic Therapies

Our laboratory focuses on the mechanisms by which epigenetic processes become misregulated in cancer and contribute to the disease phenotype. We focus on the role of DNA methylation in controlling the expression of genes during normal development and in cancer. Our work has shifted to a holistic approach in which we are interested in the interactions between processes such as DNA methylation, histone modification and nucleosomal positioning to structure the epigenome and we want to determine how mutations in the genes which modify the epigenome contribute to the cancer phenotype. We have had a longstanding interest in the mechanism of action of DNA methylation inhibitors both in the lab and in the clinic. In the clinic, we are working with several major institutions to bring epigenetic therapies to the forefront of cancer medicine.

About Epigenetics

Epigenetics may be defined as mitotically heritable changes in gene expression which are not caused by changes in the DNA sequence itself. Epigenetic processes establish the differentiated state of cells and govern how genes are used in the different cells in our bodies to allow organs and different cell types to function correctly and inherit their properties through cell division. These processes can go wrong during the formation of diseases including cancer and thus change the behavior of cells so that they don’t perform as they should. Importantly, many of these changes are potentially reversible and can be changed by treatment with appropriate drugs. Since epigenetic processes are at the root of biology they have implications in all of human development and disease.

Our Impact

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  • 121 peer-reviewed papers published in 2023
  • 62 peer-reviewed papers published in high-impact journals in 2023
  • 55 clinical trials launched to date

Peter A. Jones, Ph.D., D.Sc. (hon)

President and Chief Scientific Officer

Areas of Expertise

Epigenetics, DNA methylation, epigenetic therapies

Biography

Dr. Peter A. Jones was born in Cape Town, raised and attended college in Rhodesia (now Zimbabwe), and received his Ph.D. from the University of London. He joined the University of Southern California in 1977 and served as Director of the USC Norris Comprehensive Cancer Center between 1993 and 2011. He is currently the Chief Scientific Officer of Van Andel Institute (VAI) in Grand Rapids, Michigan. His laboratory discovered the effects of 5-azacytidine on cytosine methylation and he first established the link between DNA methylation, gene expression and differentiation. He pioneered the field of epigenetics, particularly its role in cancer, and helped develop novel therapies for cancer. Dr. Jones is a past president of the American Association for Cancer Research, a Fellow of the AACR Academy, a Fellow of the American Association for the Advancement of Science, a member of the National Academy of Sciences and a fellow of the American Academy of Arts and Sciences. He has published more than 300 scientific papers and received several honors, including the Outstanding Investigator Grant from the National Cancer Institute. He and his colleague Dr. Stephen Baylin shared the Kirk A. Landon Award for Basic Cancer Research from the AACR in 2009 and the Medal of Honor from the American Cancer Society in 2011.

SELECTED PUBLICATIONS

For a full list of publications, please visit Google Scholar here.

2023

Kang TG, Lan X, Mi T, Chen H, Alli S, Lim S-E, Bhatara S, Vasandan AB, Ward G, Bentivegna S, Jang J, Spatz ML, Han J-H, Schlotmann BC, Jespersen JS, Derenzo C, Vogel P, Yu J, Baylin S, Jones PA, O’Connell C, Grønbaek K, Youngblood B, Zebley CC. 2024. Epigenetic regulators of clonal hematopoiesis control CD8 T cell stemness during immunotherapy. Science 386(6718).

Thomas SL, Xu TH, Carpenter BL, Pierce SE, Dickson BM, Liu M, Liang G, Jones PA. 2023. DNA strand asymmetry generated by CpG hemimethylation has opposing effects on CTCF binding. Nuc Acids Res: gkad293.

Jang HJ, Hostetter G, MacFarlane AW, Madaj Z, Ross EA, Hinoue T, Kulchycki JR, Burgos RS, Tafseer M, Alpaugh RK, Schwebel CL, Kokate R, Geynisman DM, Zibelman MR, Ghatalia P, Nichols PW, Chung W, Madzo J, Hahn NM, Quinn DI, Issa JPJ, Topper MJ, Baylin SB, Shen H, Campbell KS, Jones PA, Plimack ER. 2023. A phase II trial of guadecitabine plus atezolizumab in metastatic urothelial carcinoma progressing after initial immune checkpoint inhibitor therapy. Clin Cancer Res: OF1–OF4.

Li HT, Jang HJ, Rohena-Rivera K, Liu M, Gujar H, Kulchycki J, Zhao S, Billet S, Zhou X, Weisenberger DJ, Gill I, Jones PA, Bhowmick NA, Liang G. 2023. RNA mis-splicing drives viral mimicry response after DNMTi therapy in SETD2-mutant kidney cancer. Cell Rep 42(1):112016.

2022

O’Connell CL, Baer MR, Ørskov AD, Saini SK, Duong VH, Kropf P, Hansen JW, Tsao-Wei D, Jang HS, Emadi A, Holmberg-Thyden S, Cowland J, Brinker BT, Horwood K, Burgos R, Hostetter G, Youngblood BA, Hadrup SR, Issa J-P, Jones P, Baylin SB, Siddiqi I, Gronbaek K. 2022. Safety, outcomes and T cell characteristics in patients with relapsed or refractory MDS or CMML treated with atezolizumab in combination with guadecitabine. Clin Cancer Res 28(24):5306-5316.

Zhang L, Li HT, Shereda R, Lu Q, Weisenberger DJ, O’Connell C, Machida K, An W, Lenz HJ, El-Khoueiry A, Jones PA, Liu M, Liang G. 2022. DNMT and EZH2 inhibitors synergize to activate therapeutic targets in hepatocellular carcinoma. Cancer Lett 548:215899.

Wiseman AK, Tiedemann RL, Fan H, Shen H, Madaj Z, McCabe MT, Pappalardi MB, Jones PA. 2022. Chromosome-specific retention of cancer-associated DNA hypermethylation following pharmacological inhibition of DNMTi. Commun Biol 5:528.

Zhou W, Hinoue T, Barnes B, Mitchell O, Iqbal W, Lee SM, Foy KK, Lee KH, Moyer EJ, VanderArk A, Koeman JM, Ding W, Kalkat M, Spix NJ, Eagleson B, Pospisilik JA, Szabó PE, Bartolomei M, Vander Schaaf NA, Kang L, Wiseman AK, Jones PA, Krawczyk CM, Adams M, Porecha R, Chen BH, Shen H, Laird PW. 2022. DNA methylation dynamics and dysregulation delineated by high-throughput profiling in the mouse. Cell Genom 2(7):100144.

2021

Pappalardi MB, Keenan K, Cockerill M, Kellner WA, Stowell A, Sherk C, Wong K, Pathuri S, Briand J, Steidel M, Chapman P, Groy A, Wiseman AK, McHugh CF, Campobasso N, Graves AP, Fairweather E, Werner T, Raoof A, Butlin RJ, Rueda L, Horton JR, Fosbenner DT, Zhang C, Handler JL, Muliaditan M, Mebrahtu M, Jaworski JP, McNulty DE, Burt C, Eberl HC, Taylor AN, Ho T, Merrihew S, Foley SW, Rutkowska A, Li M, Romeril SP, Goldberg K, Zhang X, Kershaw CS, Bantscheff M, Jurewicz AJ, Minthorn E, Grandi P, Patel M, Benowitz AB, Mohammad HP, Gilmartin AG, Prinjha RK, Ogilvie D, Carpenter C, Heerding D, Baylin SB, Jones PA, Cheng X, King BW, Luengo JI, Jordan AM, Waddell I, Kruger RG, McCabe MT. 2021. Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia. Nat Cancer 2(10):1002-1017.

Carpenter BL, Remba TK, Thomas SL, Madaj Z, Brink L, Tiedemann RL, Odendaal HJ, Jones PA. 2021. Ooctye age and preconceptual alcohol use are highly correlated with epigenetic imprinting of a noncoding RNA (nc886)Proc Natl Acad Sci U S A 118(12):e2026580118.

2020

Xu TH, Liu M, Zhou XE, Liang G, Zhao G, Xu HE, Melcher K, Jones PA. 2020. Structure of nucleosome-bound DNA methyltransferases DNMT3A and DNMT3B. Nature 586(7827):151-155.

Zhou W, Liang G, Molloy PL, Jones PA. 2020. DNA methylation enables transposable element-driven genome expansion. Proc Natl Acad Sci U S A 117(32):19359–19366.

Ohtani H, Ørskov AD, Helbo AS, Gillberg L, Liu M, Zhou W, Ungerstedt J, Hellström-Lindberg E, Sun W, Liang G, Jones PA, Grønbæk K. 2020. Activation of a subset of evolutionarily young transposable elements and innate immunity are linked to clinical responses to 5-azacytidine.  Cancer Res 80(12):2441–2450.

2019

Gillberg L, Ørskov AD, Nasif A, Ohtani H, Madaj Z, Hansen JW, Rapin N, Mogensen JB, Liu M, Dufva IH, Lykkesfeldt J, Hajkova P, Jones PA, Gronbeck K. 2019. Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes. Clin Epigenet 11(143)

Jones PA, Ohtani H, Chakravarthy A, DeCarvalho DD. 2019. Epigenetic therapy in immune-oncologyNat Rev Cancer 19(3):151–161.

2018

Lay FD, Kelly TK, Jones PA. 2018. Nucleosome occupancy and methylome sequencing (NOMe-seq). Methods Mol Biol 1708:267-284.

Sun W, Triche T Jr, Malvar J, Gaynon P, Sposto R, Yang X, Bittencourt H, Place AE, Messinger Y, Fraser C, Dalla-Pozza L, Salhia B, Jones PA, Wayne AS, Gore L, Cooper TM, Liang G. 2018. A phase 1 study of azacitidine combined with chemotherapy in childhood leukemia: a report from the TACL consortium. Blood131(10):1145-1148.

Carpenter BL, Zhou W, Madaj Z, DeWitt AK, Ross JP, Grønbaek K, Liang G, Clark SJ, Molloy PL, Jones PA. 2018. Mother-child transmission of epigenetic information by tunable polymorphic imprintingProc Natl Acad Sci U S A.

Liu M*, Thomas SL*, DeWitt AK*, Zhou W, Madaj ZB, Ohtani H, Baylin SB, Liang G, Jones PA. 2018. Dual inhibition of DNA and histone methyltransferases increases viral mimicry in ovarian cancer cellsCancer Res.
*Co-first authors

Lee V, Wang JS, Zahurak ML, Gootjes EC, Verheul HMW, Parkinson RM, Kerner Z, Sharma A, Rosner GL, De Jesus-Acosta A, Laheru DA, Le DT, Oganesian A, Lilly-Foreman E, Brown T, Jones PA, Baylin SB, Ahuja N, Azad NA. 2018. A phase I trial of a guadecitabine (SGI-110) and irinotecan in metastatic colorectal cancer patients previously exposed to irinotecanClin Cancer Res.

Ohtani H*, Liu M*, Zhou W, Liang G, Jones PA. 2018. Switching roles for DNA and histone methylation depend on evolutionary ages of human endogenous retrovirusesGenome Res 28(8):1147–1157.
*Co-first authors

Gillberg L, Ørskov AD, Liu M, Harsløf LBS, Jones PA, Grønbæk K. 2018. Vitamin C — A new player in regulation of the cancer epigenomeSemin Cancer Biol 51:59–67.

Van Dijk SJ, Peters TJ, Buckley M, Zhou J, Jones PA, Gibson RA, Makrides M, Muhlhausler BS, Molloy PL. 2018. DNA methylation in blood from neonatal screening cards and the association with BMI and insulin sensitivity in early childhoodInt J Obes (London) 42(1):28–35.

2017

Helbo AS, Lay FD, Jones PA, Liang G, Grønbæk K. 2017. Nucleosome positioning and NDR structure at RNA polymerase III promotersSci Rep 7:41947.

Mundbjerg K, Chopra S, Alemozaffar M, Duymich C, Lakshminarasimhan R, Nichols PW, Aron M, Siegmund KD, Ukimura O, Aron M, Stern M, Gill P, Carpten JD, Ørntoft TF, Sørensen KD, Weisenberger DJ, Jones PA, Duddalwar V, Gill I, Liang G. 2017. Identifying aggressive prostate cancer foci using a DNA methylation classifierGenome Biol 18(1):3.

Lakshminarasimhan R, Andreu-Vieyra C, Lawrenson K, Duymich CE, Gayther SA, Liang G, Jones PA. 2017. Down-regulation of ARID1A is sufficient to initiate neoplastic transformation along with epigenetic reprogramming in non-tumorigenic endometriotic cellsCancer Lett 401:11–19.

2016

Charlet J, Duymich CE, Lay FD, Mundbjerg K, Dalsgaard Sørensen K, Liang G, Jones PA. 2016. Bivalent regions of cytosine methylation and H3K27 acetylation suggest an active role for DNA methylation at enhancersMol Cell 62(3):422–431.

Becket E, Chopra S, Duymich CE, Lin JJ, You JS, Pandiyan K, Nichols PW, Siegmund KD, Charlet J, Weisenberger DJ, Jones PA, Liang G. 2016. Identification of DNA methylation-independent epigenetic events underlying clear cell renal cell carcinomaCancer Res 76(7):1954–1964.

Duymich CE, Charlet J, Yang X, Jones PA, Liang G. 2016. DNMT3B isoforms without catalytic activity stimulate gene body methylation as accessory proteins in somatic cellsNat Commun 7:11453.

Baylin SB, Jones PA. 2016. Epigenetic determinants of cancerCold Spring Harb Perspect Biol 8(9): pii:a019505.

Jones PA, Issa JP, Baylin S. 2016. Targeting the cancer epigenome for therapyNat Rev Genet 17(10):630 –641.

Liu M, Ohtani H, Zhou W, ørskov AD, Charlet J, Zhang YW, Shen H, Baylin SB, Liang G*, Grønbæk K*, Jones PA*. 2016. Vitamin C increases viral mimicry induced by 5-aza2’-deoxycytidineProc Natl Acad Sci U S A 113(37):10238–10244.
*Co-senior authors

2015

Roulois D, Yau HL, Singhania R, Wang Y, Danesh, A, Shen SY, Han H, Liang G, Jones PA, Pugh T, O’Brein C, De Carvalho DD. 2015. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcriptsCell 162(5):961–973.

Lay FD, Liu Y, Kelly TK, Witt H, Farnham PJ, Jones PA, Berman BP. 2015. The role of DNA methylation in directing the functional organization of the cancer epigenomeGenome Res 25(4): 467–477.

2014

Yang X, Han H, De Carvalho DD, Lay FD, Jones PA, Liang G. 2014. Gene body methylation can alter gene expression and is a therapeutic target in cancerCan Cell 26(4):577–590.

Taberlay PC, Statham AL, Kelly TK, Clark SJ, Jones PA. 2014. Reconfiguration of nucleosome depleted regions at distal regulatory elements accompanies DNA methylation of enhancers and insulators in cancerGenome Res 24(9):1421–1432.

Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R, Topper MJ, Luo J, Connolly RM, Azad NS, Stearns V, Pardoll DM, Davidson N, Jones PA, Slamon DJ, Baylin SB, Zahnow CA, Ahuja N. 2014. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancersOncotarget. 5(3):587–598.

Lay FD, Triche TJ, Tsai YC, Su SF, Martin SE, Daneshmand S, Skinner EC, Liang G, Chihara Y, Jones PA. 2014. Reprogramming of the intestinal epigenome by surgical tissue transpositionGenome Res 24(4):545-553.

Pedersen JS, Valen E, Velazquez AM, Parker BJ, Rasmussen M, Lindgreen S, Lilje B, Tobin DJ, Kelly TK, Vang S, Andersson R, Jones PA, Hoover CA, Tikhonov A, Prokhortchouk E, Rubin EM, Sandelin A, Gilbert MT, Krogh A, Willerslev E, Orlando L. 2014. Genome-wide nucleosome map and cytosine methylation levels of an ancient human genomeGenome Res 24(3):454–466.

Jeong KW, Andreu-Vieyra C, You JS, Jones PA, and Stallcup MR. 2014. Establishment of active chromatin structure at enhancer elements by mixed-lineage leukemia 1 to initiate estrogen-dependent gene expressionNucleic Acids Res. 42(4):2245–2256.

2013

Wrangle J, Wang W, Koch A, Easwaran H, Mohammad HP, Vendetti F, Vancriekinge W, Demeyer T, Du Z, Parsana P, Rodgers K, Yen RW, Zahnow CA, Taube JM, Brahmer JR, Tykodi SS, Easton K, Carvajal RD, Jones PA, Laird PW, Weisenberger DJ, Tsai S, Juergens RA, Topalian SL, Rudin CM, Brock MV, Pardoll D, Baylin SB. 2013. Alterations of immune response of non-small cell lung cancer with azacytidineOncotarget 4(11):2067–2079.

You JS, De Carvalho DD, Dai C, Liu M, Pandiyan K, Zhou XJ, Liang G, Jones PA. 2013. SNF5 is an essential executor of epigenetic regulation during differentiationPLoS Genet 9:e1003459.

Pandiyan K, You JS, Yang X, Dai C, Zhou XJ, Baylin SB, Jones PA, Liang G. 2013. Functional DNA demethylation is accompanied by chromatin accessibilityNucleic Acids Res 41(7):3973–3985.

2012

Kelly TK, Liu Y, Lay FD, Liang G, Berman BP, Jones PA. 2012. Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA moleculesGenome Res 22(12):2497–2506.

Jones PA. 2012. Functions of DNA methylation: islands, start sites, gene bodies and beyondNat Rev Genet 13:484-492.

You JS, Jones PA. 2012. Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell 22(1): 9–20.

De Carvalho DD, Sharma S, You JS, Su SF, Taberlay PC, Kelly TK, Yang X, Liang G, Jones PA. 2012. DNA methylation screening identifies driver epigenetic events of cancer cell survivalCan Cell 21(5):655–667.

Yang X, Noushmehr H, Han H, Andreu-Vieyra C, Liang G, Jones PA. 2012. Gene reactivation by 5-aza-2’-deoxycytidine-induced demethylation requires SRCAP-mediated H2A.Z insertion to establish nucleosome depleted regionsPLoS Genet 8:e1002604.

Sharma S, Gerke DS, Han HF, Jeong S, Stallcup MR, Jones PA, Liang G. 2012. Lysine methyltransferase G9a is not required for DNMT3A/3B anchoring to methylated nucleosomes and maintenance of DNA methylation in somatic cellsEpigenetics Chromatin 5(1):3.

Treppendahl MB, Qiu X, Søgaard A, Yang X, Nandrup-Bus C, Hother C, Andersen MK, Kjeldsen L, Möllgaard L, Hellström-Lindberg E, Jendholm J, Porse BT, Jones PA, Liang G, Grønbaek K. 2012. Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q31.1 predict outcome in AMLBlood 119(1):206–216.

2011

Andreu-Vieyra C, Lai J, Berman BP, Frenkel B, Jia L, Jones PA, Coetzee GA. 2011. Dynamic nucleosome-depleted regions at androgen receptor enhancers in the absence of ligand in prostate cancer cellsMol Cell Biol 31(23):4648–4662.

Han H, Cortez CC, Yang X, Nichols PW, Jones PA, Liang G. 2011. DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoterHum Mol Genet 20(22):4299–4310.

Taberlay PC, Kelly TK, Liu CC, You JS, De Carvalho DD, Miranda TB, Zhou XJ, Liang G, Jones PA. 2011. Polycomb-repressed genes have permissive enhancers that initiate reprogrammingCell 147(6):1283–1294.

Josh (Hyo Sik) Jang, Ph.D.

VAI Fellow, Peter Jones Laboratory

Single cell resolution of immune landscape in cancer therapy

HyeonJin Kim

Assistant Research Technician, Department of Epigenetics

Hyein Lee

Student Intern, Peter Jones Laboratory

Minmin Liu, Ph.D.

Senior Research Scientist, Department of Epigenetics

Seth Nelson

Assistant Research Technician, Department of Epigenetics

Audrey Nguyen

Assistant Research Technician, Department of Epigenetics

Amy Nuffesse

Senior Administrative Assistant II, Department of Epigenetics

Rachel Shereda, B.S.

Research Technician, Department of Epigenetics

Stacey Thomas, Ph.D.

Senior Laboratory Manager, Department of Epigenetics

Guillermo Urrutia, M.D.

Research Scientist, Department of Epigenetics

Xiaoyan Xie, Ph.D.

Postdoctoral Fellow, Peter Jones Laboratory

The role of DNA methylation in controlling gene expression during cancer development

Jueng Soo You, Ph.D.

Visiting Scientist, Department of Epigenetics

Lab Alumni

Brittany Carpenter, Ph.D.

Postdoctoral Fellow

Justin Kulchycki

Senior Research Technician

Hyein Lee

Student Intern

Hitoshi Ohtani, Ph.D.

Postdoctoral Fellow

Anthony Popkie, Ph.D.

Laboratory Manager

Rochelle Tiedemann, Ph.D.

Research Scientist

Ashley Wiseman, M.S.

Research Associate

Tinghai (Peter) Xu, Ph.D.

Research Scientist

Wanding Zhou, Ph.D.

Postdoctoral Fellow