- Ph.D., Molecular Genetics, Emory University, Atlanta, GA, 1997
- B.A., Microbiology, Miami University, Oxford, OH, 1991
Dr. Peter Jones has been investigating epigenetic mechanisms of gene regulation for most of his career and has been working on pathogenic mechanisms in facioscapulohumeral muscular dystrophy (FSHD) since 2003. As an undergraduate, an exciting research experience investigating ice-nucleating active bacteria with Dr. Marcia Lee turned his interests away from medical school and towards a career in biomedical research. Dr. Jones earned his PhD with Dr. Jeremy Boss at Emory University, working on gene regulation by primary immune response cytokines. His thesis work suggested a key role for enhancer chromatin structure in cytokine-mediated gene regulation. To further pursue the emerging role of chromatin as a regulatory mechanism, Dr. Jones did his post-doctoral fellowship at NIH with Dr. Alan P. Wolffe, one of the leaders in chromatin biology at the time. At NIH, Dr. Jones expanded his training into biochemistry and developmental biology, with a focus on epigenetics, DNA methylation, and chromatin remodeling. In 2001, Dr. Jones took a position as Assistant Professor at the University of Illinois at Urbana-Champaign and began identifying novel DNA methylation and chromatin remodeling complexes using Xenopus as a model system. When a graduate student introduced him to FSHD-an epigenetic disease-the lab began several exploratory projects and now works on FSHD translational research full-time. In 2008, Dr. Jones teamed up with his wife, Dr. Takako Jones, an expert in cell and developmental biology, and the two have been working as co-PIs ever since. The Jones lab has moved several times since UIUC, first joining the Boston Biomedical Research Institute, then the University of Massachusetts Medical School, and now the University of Nevada, Reno School of Medicine. Each institute has allowed us to develop new technologies and expertise for use in our FSHD research projects. Published studies from our lab utilize biochemistry, developmental biology, cell biology, genomics, and molecular biology approaches. Model systems include C. elegans, Xenopus laevis, honeybee, Drosophila, mouse, and primary mouse and human myogenic cells. The common theme of the lab continues to be exploring the epigenetics of muscle development and disease.
Drs. Peter and Takako Jones function as co-PIs, combining expertise in gene regulation, biochemistry, and chromatin with expertise in cell, developmental, and molecular biology. Together we investigate epigenetic mechanisms of gene regulation, focusing on the combined roles of DNA methylation, histone post-translational modifications, active and repressive chromatin regulators, and noncoding RNAs.
We use a wide range of approaches, including biochemistry, cell biology, developmental biology, proteomics, and epigenomics, to investigate the epigenetic mechanisms that function during normal muscle development and establish and maintain disease states. Our experimental approaches have utilized several different model organisms including mouse, Drosophila, and primary human cell culture models and in vitrosystems. Overall, we aim to design therapeutic approaches targeting the epigenetic regulatory mechanisms involved in human disease with a particular focus on myopathies. Our research covers three main areas:
Epigenetics of muscle development and disease
We use Facioscapulohumeral muscular dystrophy (FSHD) as a model to investigate epigenetic mechanisms of gene regulation. The genetic criteria for FSHD are merely disease permissive, with all forms of clinical FSHD exhibiting epigenetic dysregulation of the chromosome 4q35 D4Z4 macrosatellite array. The epigenetic mechanisms that go awry in FSHD include DNA methylation, histone post-translational modifications, Polycomb Group proteins, lncRNAs, RNA-dependent DNA methylation, and nuclear organization.
Engineering novel disease models for therapeutic development and preclinical testing
While we have used many animal models, including Drosophila and C. elegans, our lab is now focused on the design of human cellular and mouse models of FSHD for therapeutic development and pre-clinical testing. These models are based on aberrant expression of DUX4, a developmentally important gene that has been implicated in mediating FSHD pathophysiology. Our FSHD disease models are used to test small molecule, ncRNA, and CRISPR-based therapeutic approaches.
RNA-binding proteins involved in development and disease
We focus on two highly conserved proteins, FRG1 and MeCP2, which we have identified as RNA-binding proteins. In addition to interacting with select mRNAs, FRG1 is also an actin bundling protein critical for muscle development and a direct transcriptional target of the DUX4-FL transcription factor implicated in FSHD. MeCP2 is an epigenetic regulator critical for neuronal development and the gene most commonly mutated in Rett Syndrome.
- Charis L. Himeda, Takako I. Jones, and Peter L. Jones. . CRISPR/dCas9-mediated transcriptional inhibition ameliorates the epigenetic dysregulation at D4Z4 and represses DUX4-fl in FSH muscular dystrophy. Molecular Therapy 24(3):527-35. PMC4786914 [This work was highlighted in The Washington Post, The Huffington Post, Boston Business Weekly, and Vibe; Featured on the websites for the FSH Society, the Chris Carrino Foundation for FSHD, AMIS FSH, and FSHD Global. This work earned Dr. Himeda the FSH Society "Young Investigator of the Year" award.].
- Takako I. Jones, Charis L. Himeda, Daniel P. Perez, and Peter L. Jones. . Large family cohorts of lymphoblastoid cells provide a new cellular model for investigating facioscapulohumeral muscular dystrophy. In Revision.
- ND Shaw*, H Brand*, ZA Kupchinsky, H Bengani, L Plummer, S Erdin, Takako I Jones, KA Williamson, J Rainger, K Samocha, R Collins, JR Willer, A Lek, M Lek, M Nassan, C Golzio, S Pereira, T Kammin, D Lucente, A Silva, C Seabra, Y An, A Stortchevoi, M Ansari, JK Rainger, S Joss, J Clayton-Smith, MF Lippincott, S Singh, N Patel, J Law, N Ferraro, A Verloes, A Rauch, K Steindl, D Sato, K Yoshiura, N Okamoto, C Jacobsen, J Tryggestad, S Chernausek, LA Schimmenti, B Brasseur, C Cesaretti, JE García-Ortiz, TP Buitrago, OP Silva, JD Hoffman, W Mühlbauer, KW Ruprecht, B Loeys, A Kaindl, C-H Cho, C Morton, V van Heyningen, E Liao, JE Hall, SB Seminara, JF Gusella, D Macarthur, JA Marsh, JM Graham, Jr, AE Lin, N Katsanis, Peter L Jones, WF Crowley, Jr, EE Davis, David R FitzPatrick**, Michael E Talkowski**. . Missense Mutations in SMCHD1 are Associated with Isolated Arhinia, Bosma Arhinia Microphthalmia Syndrome, and Facioscapulohumeral Muscular Dystrophy Type 2. Nature Genetics (In Press).
- Charis L. Himeda, Takako I. Jones, and Peter L. Jones. . Scalpel or Straitjacket; CRISPR/Cas9 approaches to muscular dystrophy. Invited Forum Article. Trends in Pharmacological Sciences 37(4):249-51.
- Takako I. Jones, Megan Parilla, and Peter L. Jones. . Transgenic Drosophila for investigating DUX4 and FRG1, two genes associated with facioscapulohumeral muscular dystrophy (FSHD). PLoS ONE 11(3):e0150938. PMC4778869.
- Angela Lek, Fedik Rahimov, Peter L. Jones and Louis M. Kunkel. . Emerging preclinical animal models for FSHD. Trends in Molecular Medicine, 21:295-306.
- Charis L. Himeda, Takako I. Jones and Peter L. Jones. . Facioscapulohumeral muscular dystrophy as a model for epigenetic regulation and disease. Antioxidants & Redox Signaling 22(6):1463-82. PMC4432493.
- Takako I. Jones, Oliver D. King, Charis L. Himeda, Sachiko Homma, Jennifer C. J. Chen, Mary Lou Beermann, Chi Yan, Charles P. Emerson, Jr, Jeffrey B. Miller, Kathryn R. Wagner and Peter L. Jones. . Individual epigenetic status of the pathogenic D4Z4 macrosatellite correlates with disease in facioscapulohumeral muscular dystrophy. Clinical Epigenetics, 7:37. PMC4405830.
- Yuanfan Zhang, Oliver D. King, Fedik Rahimov, Takako I. Jones, Christopher W. Ward, Jaclyn P. Kerr, Naili Liu, Charles P. Emerson Jr, Louis M. Kunkel, Terence A. Partridge and Kathryn R. Wagner. . Human skeletal muscle xenograph as a new preclinical model for muscle disorders. Human Molecular Genetics, 23:3180-3188. PMCID: PMC4030773.
- Takako I. Jones, Chi Yan, Peter C. Sapp, Diane McKenna-Yasek, Peter B. Kang, Colin Quinn, Johnny S. Salameh, Oliver D. King and Peter L. Jones. . Identifying diagnostic DNA methylation profiles for facioscapulohumeral muscular dystrophy in blood and saliva using bisulfite sequencing. Clinical Epigenetics 6:23.
- Charis L. Himeda, Celine Debarnot, Sachiko Homma, Mary Lou Beermann, Jeffrey B. Miller, Peter L. Jones* and Takako I. Jones*. . Myogenic enhancers regulate expression of the facioscapulohumeral muscular dystrophy associated DUX4 gene. Molecular and Cellular Biology 34(11):1942-55. PMCID: PMC4019064.
- Satomi Mitsuhashi, Steven E. Boyden, Elicia A. Estrella, Takako I. Jones, Fedik Rahimov, Timothy W. Yu, Basil T. Darras, Anthony A. Amato, Rebecca D. Folkerth, Peter L. Jones, Louis M. Kunkel and Peter B. Kang. . Exome sequencing identifies a novel SMCHD1 mutation in facioscapulohumeral muscular dystrophy 2. Neuromuscular Disorders, 23:975-980. PMCID: PMC3851942.
- Gary T. Morgan, Peter L. Jones and Michel Bellini. . Association of modified cytosines and the methylated DNA-binding protein MeCP2 with distinctive structural domains of lampbrush chromatin. Chromosome Research, 20:925-30. PMCID: PMC3565088.
- Qian Liu, Takako I. Jones, Rebecca A. Bachmann, Lauren Rogowski, Mitchell Meghpara, Benjamin D. Williams and Peter L. Jones. . C. elegans PAT-9 is a nuclear zinc finger protein critical for the assembly of muscle attachments. Cell and Bioscience, 2:18. PMCID: PMC3419604.
- Takako I. Jones, Jennifer C.J. Chen, Fedik Rahimov, Sachiko Homma, Patricia Arashiro, Mary Lou Beermann, Oliver D. King, Jeffrey B. Miller, Louis M. Kunkel, Charles P. Emerson, Jr, Kathryn Wagner and Peter L. Jones. . Facioscapulohumeral muscular dystrophy family studies of DUX4 expression: Evidence for disease modifiers and a quantitative model of pathogenesis. Human Molecular Genetics, 21:4419-4430. PMCID: PMC3459465.
- Steven W. Long, Jenny Y.Y. Ooi, Peter M. Yau and Peter L. Jones. . A brain-derived methyl-CpG binding protein 2 (MeCP2) complex supports a role for MeCP2 in RNA processing. Bioscience Reports 31(5):333-343. PMCID: PMC3148018.
- Meredith Hanel, Chia-Yun Jessica Sun, Takako I. Jones, Steven W. Long, Simona Zanotti, Derek Milner, and Peter L. Jones. . Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a dynamic nuclear and sarcomeric protein. Differentiation 81:107-118. PMCID: PMC3030934.
- Chia-Yun Jessica Sun, Silvana van Koningsbruggen, Steven W. Long, Kirsten Straasheijm, Rinse Klooster, Takako I. Jones, Michel Bellini, Lyne Levesque, William M. Brieher, Silvère M. van der Maarel, and Peter L. Jones. . FRG1 is a dynamic RNA-associated actin-bundling protein. Journal of Molecular Biology, 411:397-416. PMCID: PMC3143299.
- Ozren Bogdanovic, Steven W. Long, Simon van Heeringen, Arjen Brinkman, Hendrik G. Stunnenberg, Peter L. Jones, and Gert Jan C. Veenstra. . Temporal uncoupling of the DNA methylome and transcriptional repression during embryogenesis. Genome Research 21:1313-1327. PMCID: PMC3149498.
- Qian Liu, Takako Iida Jones, Vivian W. Tang, William M. Brieher, and Peter L. Jones. . Facioscapulohumeral region gene-1 (FRG-1) is an actin bundling protein associated with muscle attachment sites. Journal of Cell Science 123:1116-1123. PMCID: PMC2844320.
- Ryan D. Wuebbles, Steven W. Long, Meredith L. Hanel, and Peter L. Jones. . Testing the effects of FSHD candidate gene expression in vertebrate development. International Journal of Clinical and Experimental Pathology 3(4):386-400. PMCID: PMC2872745.
- Ryan D. Wuebbles, Meredith Hanel, and Peter L. Jones. . FSHD region gene 1 (FRG1) is crucial for angiogenesis linking FRG1 to facioscapulohumeral muscular dystrophy-associated vasculopathy. Disease Models and Mechanisms 2:267-274. PMCID: PMC2675802.
- Meredith Hanel, Ryan D. Wuebbles, and Peter L. Jones. . Muscular dystrophy candidate gene FRG1 is critical for muscle development. Developmental Dynamics 238:1502-1512. PMCID: PMC2964887.
- Assam El-Osta, Daniella Brasacchio, Dachun Yao, Alessandro Pocai, Peter L. Jones, Robert G. Roeder, Mark E. Cooper, and Michael Brownlee. . Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. Journal of Experimental Medicine 205:2409-2417. PMCID: PMC2556800.
- Ryan Wuebbles and Peter L. Jones. . Engineered telomeres in transgenic Xenopus laevis. Transgenic Research 16:377-84.
- Brent Beenders, Peter L. Jones, and Michel Bellini. . The tripartite motif (TRIM) of nuclear factor 7 is required for its association with transcription units. Molecular and Cellular Biology 27:2615-2624.
- Ying Wang, Mireia Jorda, Peter L. Jones, Ryszard Maleszka, Xu Ling, Hugh M. Robertson, Craig A. Mizzen, Miguel A. Peinado, Gene E. Robinson. . Functional CpG methylation system in a social insect. Science 314:645-647.
- The Honeybee Genome Sequencing Consortium led by George M. Weinstock and Gene E. Robinson. Gene regulation group: R. Maleszka, D.B. Weaver, G.V. Amdam, J.M. Anzola, K.S. Campbell, K.L. Childs, D. Collinge, M.A. Crosby, C.M. Dickens, C.G. Elsik, K.H.J. Gordon, L.S. Grametes, C.M. Grozinger, Peter L. Jones, M. Jorda, X. Ling, B.B. Matthews, J. Miller, N.V. Milshina, C. Mizzen, M.A. Peinado, J.T. Reese, J.G. Reid, H.M. Robertson, G.E. Robinson, S.M. Russo, A.J. Schroeder, S.E. St. Pierre, Y. Wand, P. Zhou. . Insights into social insects from the genome of the honeybee Apis mellifera. Nature 443: 931-949.
- KN Harikrishnan, Sharmista Pal, M Yarski,, Emma K. Baker, Maggie Chow, MG deSilva, J Okabe, Li Wang, Peter L. Jones, Said Sif, and Assam El-Osta. . Reply to "Testing for association between MeCP2 and the brahma-associated SWI/SNF chromatin-remodeling complex.". Nature Genetics 38:964-967.
- KN Harikrishnan, Maggie Chow, Emma K. Baker, Sharmista Pal, Sahar Bassal, Daniella Brasacchio, Li Wang, Jeff M. Craig, Peter L. Jones, Said Sif, and Assam El-Osta. . Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing. Nature Genetics 37:254-64.
- Ryan D. Wuebbles and Peter L. Jones. . DNA repair in a chromatin environment. Cellular and Molecular Life Sciences. 61:48-53.
- Peter L. Jones and Yun-Bo Shi. . N-CoR-HDAC Corepressor Complexes: Roles in Transcriptional Regulation by Nuclear Hormone Receptors. Current Topics in Microbiology and Immunology 274: 237-268.
- Laurent M. Sachs, Peter L. Jones, Emmanuelle Havis, Nicole Rouse, Barbara Demeneix, and Yun-Bo Shi. . Nuclear receptor corepressor recruitment by unliganded thyroid hormone receptor in gene repression during Xenopus laevis development. Molecular and Cellular Biology 22:8527-8538.
- Laurent M. Sachs, Peter Jones, Shaochung Hsia, and Yun-Bo Shi. . Chromatin remodeling and developmental gene regulation by thyroid hormone receptor. Gene Therapy and Molecular Biology 5:101-110.
- Peter L. Jones, Laurent M. Sachs, Nicole Rouse, Paul A. Wade, and Yun-Bo Shi. . Multiple N-CoR complexes contain distinct histone deacetylases. Journal of Biological Chemistry 276:8807-8812.
- Walter Stunkel, Slimane Ait-Si-Ali, Peter L. Jones, and Alan P. Wolffe. . Programming the transcriptional state of replicating methylated DNA. Journal of Biological Chemistry 276:20743-20749.
- Keith D. Robertson, Slimane Ait-Si-Ali, Tomoki Yokochi, Paul A. Wade, Peter L. Jones, and Alan P. Wolffe. . DNMT1 forms a complex with Rb, E2f1 and HDAC1 and represses transcription from E2F-responsive promoters. Nature Genetics 25:338-342.
- Laurent M. Sachs, Sashko Damjanovski, Peter L. Jones, Qing Li, Tosikazu Amano, Shuichi Ueda, Yun-Bo Shi, and Atsuko Ishizuya-Oka. . Dual functions of thyroid hormone receptors during Xenopus development. Comparative Biochemistry and Physiology 126:199-211.
- Alan P. Wolffe, Peter L. Jones, and Paul A. Wade. . DNA Demethylation. PNAS USA 96: 5894-96.
- Peter L. Jones*, Danielle Vermaak*, Paul A. Wade*, Yun-bo Shi, and Alan P. Wolffe. . Functional analysis of the SIN3-histone deacetylase RPD3-RbAp48-histone H4 connection in the Xenopus oocyte-evidence for a default pathway of deacetylase mediated transcriptional repression. Molecular and Cellular Biology 19:5847-5860. [*These three authors provided an equal contribution].
- Paul A. Wade, Anne Gegonne, Peter L. Jones, Esteban Ballestar, Florence Aubry, and Alan P. Wolffe. . Mi-2 complex couples DNA methylation to chromatin remodeling and histone deacetylation. Nature Genetics 23:62-66.
- Peter L. Jones and Alan P. Wolffe. . Relationships between chromatin organization and DNA methylation in determining gene expression. Seminars in Cancer Biology 9:339-347.
- Paul A. Wade, Peter L. Jones, Danielle Vermaak, and Alan P. Wolffe. . A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase. Current Biology, 8:843-846.
- Peter L. Jones, Gert Jan C. Veenstra, Paul A. Wade, Danielle Vermaak, Stefan U. Kass, Nicoletta Landsberger, John Strouboulis, and Alan P. Wolffe. . Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nature Genetics, 19:187-191.
- Yun-Bo Shi, Laurent M. Sachs, Peter L. Jones, Qing Li, and A. Ishizuya-Oka. . Thyroid hormone regulation of Xenopus laevis metamorphosis: Function of TRs and roles of ECM remodeling. Wound Repair and Regeneration 6:314-322.
- Elizabeth R. Smith, Peter L. Jones, Jeremy M. Boss, and Al H. Merrill. . Changing J774A.1 cells to new media perturbs multiple signaling pathways, including the modulation of protein kinase C by endogenous sphingoid bases. Journal of Biological Chemistry 272:5640-5646.
- Peter L. Jones, Dongsheng Ping, and Jeremy M. Boss. . Tumor necrosis factor-α and Interleukin-1β regulate the murine manganese superoxide dismutase gene through a complex intronic enhancer involving C/EBP-β and NF-κB. Molecular and Cellular Biology, 17:6970-6981.
- Dongsheng Ping, Peter L. Jones, and Jeremy M. Boss. . TNF regulates the in vivo occupancy of both distal and proximal regulatory regions of the MCP-1/JE gene. Immunity, 4:455-469.
- Peter L. Jones, Gary Kucera, Helen Gordon, and Jeremy M. Boss. . Cloning and characterization of the murine manganous superoxide dismutase-encoding gene. Gene, 153:155-161.