Alexander Ruthenburg

Associate Professor
Websites
Research Summary
The unifying theme of my lab is the elucidation of molecular mechanisms underlying management chromatin, the physiological form of the genome. In particular, we are interested in how post translational modifications to histones, newly appreciated DNA modifications and noncoding RNA can control chromatin structure. Our research spans several traditional disciplines, ranging from discovery biochemistry and genome-scale measurements to mechanistic characterization with biophysical methods coupled with X-Ray structure to address fundamental questions in chromatin biology. We have pioneered new technologies to make quantitative local measurements of chromatin components. Projects ideally will transition from discovery biology to detailed molecular and structural investigation.
Keywords
Chromatin, Epigenetics, Biochemistry, Genomics, Regulation of Gene Expression, Chromatin Immunoprecipitation, Chromatin Associated RNA, Epigenomics, Epigenetic Process, Transcriptional Activation, Nucleosomes
Education
  • Rockefeller University , New York, NY, Postdoctoral Fellow Chromatin biochemsitry and epigenetics 8/2010
  • Harvard University , Cambridge, MA, Ph.D. Chemical and Structural biology 9/2005
  • Carleton College, Northfield, MN, B.A. Chemistry 6/1999
Awards & Honors
  • 2000 - 2004 National Science Foundation Graduate Research Fellow Harvard University
  • 2007 - 2010 Irvington Institute Research Fellowship Cancer Research Institute
  • 2010 - 2012 Junior Investigator Chicago Biomedical Consortium
  • 2010 - 2015 Neubauer Family Foundation Assistant Professor University of Chicago
  • 2011 - Kavli Fellow National Academy of Sciences
  • 2013 - 2017 New Scholar in Aging Ellison Medical Foundation
Publications
  1. Bennett RL, Bele A, Small EC, Will CM, Nabet B, Oyer JA, Huang X, Ghosh RP, Grzybowski AT, Yu T, Zhang Q, Riva A, Lele TP, Schatz GC, Kelleher NL, Ruthenburg AJ, Liphardt J, Licht JD. A Mutation in Histone H2B Represents a New Class of Oncogenic Driver. Cancer Discov. 2019 Jul 23. View in: PubMed

  2. Shah RN, Grzybowski AT, Cornett EM, Johnstone AL, Dickson BM, Boone BA, Cheek MA, Cowles MW, Maryanski D, Meiners MJ, Tiedemann RL, Vaughan RM, Arora N, Sun ZW, Rothbart SB, Keogh MC, Ruthenburg AJ. Examining the Roles of H3K4 Methylation States with Systematically Characterized Antibodies. Mol Cell. 2018 10 04; 72(1):162-177.e7. View in: PubMed

  3. Karki S, Kennedy DE, Mclean K, Grzybowski AT, Maienschein-Cline M, Banerjee S, Xu H, Davis E, Mandal M, Labno C, Powers SE, Le Beau MM, Dinner AR, Singh H, Ruthenburg AJ, Clark MR. Regulated Capture of V? Gene Topologically Associating Domains by Transcription Factories. Cell Rep. 2018 Aug 28; 24(9):2443-2456. View in: PubMed

  4. Maganti HB, Jrade H, Cafariello C, Manias Rothberg JL, Porter CJ, Yockell-Lelièvre J, Battaion HL, Khan ST, Howard JP, Li Y, Grzybowski AT, Sabri E, Ruthenburg AJ, Dilworth FJ, Perkins TJ, Sabloff M, Ito CY, Stanford WL. Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy. Cancer Discov. 2018 11; 8(11):1376-1389. View in: PubMed

  5. Gupta A, Xu J, Lee S, Tsai ST, Zhou B, Kurosawa K, Werner MS, Koide A, Ruthenburg AJ, Dou Y, Koide S. Facile target validation in an animal model with intracellularly expressed monobodies. Nat Chem Biol. 2018 09; 14(9):895-900. View in: PubMed

  6. Yang XH, Nadadur RD, Hilvering CR, Bianchi V, Werner M, Mazurek SR, Gadek M, Shen KM, Goldman JA, Tyan L, Bekeny J, Hall JM, Lee N, Perez-Cervantes C, Burnicka-Turek O, Poss KD, Weber CR, de Laat W, Ruthenburg AJ, Moskowitz IP. Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm. Elife. 2017 12 27; 6. View in: PubMed

  7. Chen Z, Notti RQ, Ueberheide B, Ruthenburg AJ. Quantitative and Structural Assessment of Histone Methyllysine Analogue Engagement by Cognate Binding Proteins Reveals Affinity Decrements Relative to Those of Native Counterparts. Biochemistry. 2018 01 23; 57(3):300-304. View in: PubMed

  8. Werner MS, Sullivan MA, Shah RN, Nadadur RD, Grzybowski AT, Galat V, Moskowitz IP, Ruthenburg AJ. Chromatin-enriched lncRNAs can act as cell-type specific activators of proximal gene transcription. Nat Struct Mol Biol. 2017 Jul; 24(7):596-603. View in: PubMed

  9. Hattori T, Lai D, Dementieva IS, Montaño SP, Kurosawa K, Zheng Y, Akin LR, Swist-Rosowska KM, Grzybowski AT, Koide A, Krajewski K, Strahl BD, Kelleher NL, Ruthenburg AJ, Koide S. Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation. Proc Natl Acad Sci U S A. 2016 Feb 23; 113(8):2092-7. View in: PubMed

  10. Werner MS, Ruthenburg AJ. Nuclear Fractionation Reveals Thousands of Chromatin-Tethered Noncoding RNAs Adjacent to Active Genes. Cell Rep. 2015 Aug 18; 12(7):1089-98. View in: PubMed

  11. Rothbart SB, Dickson BM, Raab JR, Grzybowski AT, Krajewski K, Guo AH, Shanle EK, Josefowicz SZ, Fuchs SM, Allis CD, Magnuson TR, Ruthenburg AJ, Strahl BD. An Interactive Database for the Assessment of Histone Antibody Specificity. Mol Cell. 2015 Aug 06; 59(3):502-11. View in: PubMed

  12. Grzybowski AT, Chen Z, Ruthenburg AJ. Calibrating ChIP-Seq with Nucleosomal Internal Standards to Measure Histone Modification Density Genome Wide. Mol Cell. 2015 Jun 04; 58(5):886-99. View in: PubMed

  13. Chen Z, Grzybowski AT, Ruthenburg AJ. Traceless semisynthesis of a set of histone 3 species bearing specific lysine methylation marks. Chembiochem. 2014 Sep 22; 15(14):2071-5. View in: PubMed

  14. Hattori T, Taft JM, Swist KM, Luo H, Witt H, Slattery M, Koide A, Ruthenburg AJ, Krajewski K, Strahl BD, White KP, Farnham PJ, Zhao Y, Koide S. Recombinant antibodies to histone post-translational modifications. Nat Methods. 2013 Oct; 10(10):992-5. View in: PubMed

  15. Malecek K, Ruthenburg A. Validation of histone-binding partners by peptide pull-downs and isothermal titration calorimetry. Methods Enzymol. 2012; 512:187-220. View in: PubMed

  16. Mohrig JR, Beyer BG, Fleischhacker AS, Ruthenburg AJ, John SG, Snyder DA, Nyffeler PT, Noll RJ, Penner ND, Phillips LA, Hurley HL, Jacobs JS, Treitel C, James TL, Montgomery MP. Does activation of the anti proton, rather than concertedness, determine the stereochemistry of base-catalyzed 1,2-elimination reactions? Anti stereospecificity in E1cB eliminations of ß-3-trifluoromethylphenoxy esters, thioesters, and ketones. J Org Chem. 2012 Mar 16; 77(6):2819-28. View in: PubMed

  17. Werner M, Ruthenburg AJ. The United States of histone ubiquitylation and methylation. Mol Cell. 2011 Jul 08; 43(1):5-7. View in: PubMed

  18. Ruthenburg AJ, Li H, Milne TA, Dewell S, McGinty RK, Yuen M, Ueberheide B, Dou Y, Muir TW, Patel DJ, Allis CD. Recognition of a mononucleosomal histone modification pattern by BPTF via multivalent interactions. Cell. 2011 May 27; 145(5):692-706. View in: PubMed

  19. Milne TA, Kim J, Wang GG, Stadler SC, Basrur V, Whitcomb SJ, Wang Z, Ruthenburg AJ, Elenitoba-Johnson KS, Roeder RG, Allis CD. Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis. Mol Cell. 2010 Jun 25; 38(6):853-63. View in: PubMed

  20. Ruthenburg AJ, Li H, Patel DJ, Allis CD. Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol. 2007 Dec; 8(12):983-94. View in: PubMed

  21. Taverna SD, Li H, Ruthenburg AJ, Allis CD, Patel DJ. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol. 2007 Nov; 14(11):1025-1040. View in: PubMed

  22. Ruthenburg AJ, Allis CD, Wysocka J. Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol Cell. 2007 Jan 12; 25(1):15-30. View in: PubMed

  23. Dou Y, Milne TA, Ruthenburg AJ, Lee S, Lee JW, Verdine GL, Allis CD, Roeder RG. Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat Struct Mol Biol. 2006 Aug; 13(8):713-9. View in: PubMed

  24. Ruthenburg AJ, Wang W, Graybosch DM, Li H, Allis CD, Patel DJ, Verdine GL. Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex. Nat Struct Mol Biol. 2006 Aug; 13(8):704-12. View in: PubMed

  25. Losey HC, Ruthenburg AJ, Verdine GL. Crystal structure of Staphylococcus aureus tRNA adenosine deaminase TadA in complex with RNA. Nat Struct Mol Biol. 2006 Feb; 13(2):153-9. View in: PubMed

  26. Wei H, Ruthenburg AJ, Bechis SK, Verdine GL. Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase. J Biol Chem. 2005 Nov 04; 280(44):37041-7. View in: PubMed

  27. Ruthenburg AJ, Graybosch DM, Huetsch JC, Verdine GL. A superhelical spiral in the Escherichia coli DNA gyrase A C-terminal domain imparts unidirectional supercoiling bias. J Biol Chem. 2005 Jul 15; 280(28):26177-84. View in: PubMed