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Faculty of Health and Life Sciences

Dr Johannes Rack

Dr Johannes Rack

 J.Rack@exeter.ac.uk

 Geoffrey Pope 

 

Geoffrey Pope Building, University of Exeter , Stocker Road, Exeter, EX4 4QD, UK


Overview

Dr Johannes Rack joined the MRC CMM on an MRC Career Development Award in April 2023. Johannes’ research focuses on the role of ADP-ribosylation signaling in the control of genomic integrity and virulence of the major human pathogen Aspergillus fumigatus. Maintaining genomic integrity is essential for the survival of the fungus in the infection environment as well as one of major targets of the human immune system to combat the invading pathogen. A mechanistic understanding of the underlying process of how ADP-ribosylation signalling is established and removed as well as which cellular processes are controlled by it will allow us develop novel therapeutic strategies to combat live-threatening fungal infections.

Qualifications

2013 PhD Molecular Biology, University of Bergen, Norway

2009 Dipl Biochemistry, Leibniz University Hannover & Hannover Medical School (MHH), Germany

Career

April 2023: MRC Career Development Award Fellow

2014 – 2023: Postdoctoral Researcher, Sir William Dunn School of Pathology, University of Oxford, UK

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Publications

Journal articles

Zhang Z, Fu J, Rack JGM, Li C, Voorneveld J, Filippov DV, Ahel I, Luo Z-Q, Das C (2024). Legionella metaeffector MavL reverses ubiquitin ADP-ribosylation via a conserved arginine-specific macrodomain. Nat Commun, 15(1). Abstract.  Author URL.
Madern JM, Voorneveld J, Rack JGM, Kistemaker HAV, Ahel I, van der Marel GA, Codée JDC, Filippov DV (2023). 4-Thioribose Analogues of Adenosine Diphosphate Ribose (ADPr) Peptides. Organic Letters, 25(27), 4980-4984.
Suskiewicz MJ, Prokhorova E, Rack JGM, Ahel I (2023). ADP-ribosylation from molecular mechanisms to therapeutic implications. Cell, 186(21), 4475-4495. Abstract.
Tashiro K, Wijngaarden S, Mohapatra J, Rack JGM, Ahel I, Filippov DV, Liszczak G (2023). Chemoenzymatic and Synthetic Approaches to Investigate Aspartate- and Glutamate-ADP-Ribosylation. Journal of the American Chemical Society, 145(25), 14000-14009.
Minnee H, Chung H, Rack JGM, van der Marel GA, Overkleeft HS, Codée JDC, Ahel I, Filippov DV (2023). Four of a Kind: a Complete Collection of ADP-Ribosylated Histidine Isosteres Using Cu(I)- and Ru(II)-Catalyzed Click Chemistry. The Journal of Organic Chemistry, 88(15), 10801-10809.
Schuller M, Raggiaschi R, Mikolcevic P, Rack JGM, Ariza A, Zhang Y, Ledermann R, Tang C, Mikoc A, Ahel I, et al (2023). Molecular basis for the reversible ADP-ribosylation of guanosine bases. Molecular Cell, 83(13), 2303-2315.e6.
Đukić N, Strømland Ø, Elsborg JD, Munnur D, Zhu K, Schuller M, Chatrin C, Kar P, Duma L, Suyari O, et al (2023). PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities. Sci Adv, 9(37). Abstract.  Author URL.
Fontana P, Buch-Larsen SC, Suyari O, Smith R, Suskiewicz MJ, Schützenhofer K, Ariza A, Rack JGM, Nielsen ML, Ahel I, et al (2023). Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling. Nature Communications, 14(1). Abstract.
Minnee H, Rack JGM, van der Marel GA, Overkleeft HS, Codée JDC, Ahel I, Filippov DV (2023). Solid‐Phase Synthesis and Biological Evaluation of Peptides ADP‐Ribosylated at Histidine. Angewandte Chemie, 136(4). Abstract.
Minnee H, Rack JGM, van der Marel GA, Overkleeft HS, Codée JDC, Ahel I, Filippov DV (2023). Solid‐Phase Synthesis and Biological Evaluation of Peptides ADP‐Ribosylated at Histidine. Angewandte Chemie International Edition, 63(4).
Hlousek-Kasun A, Mikolcevic P, Rack JGM, Tromans-Coia C, Schuller M, Jankevicius G, Matkovic M, Bertosa B, Ahel I, Mikoc A, et al (2022). <i>Streptomyces</i><i> coelicolor</i> macrodomain hydrolase SCO6735 cleaves thymidine-linked ADP-ribosylation of DNA. COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL, 20, 4337-4350.  Author URL.
Minnee H, Rack JGM, van der Marel GA, Overkleeft HS, Codee JDC, Ahel I, Filippov DV (2022). Mimetics of ADP-Ribosylated Histidine through Copper(I)-Catalyzed Click Chemistry. ORGANIC LETTERS, 24(21), 3776-3780.  Author URL.
Beijer D, Agnew T, Rack JGM, Prokhorova E, Deconinck T, Ceulemans B, Peric S, Rasic VM, De Jonghe P, Ahel I, et al (2021). Biallelic <i>ADPRHL2</i> mutations in complex neuropathy affect ADP ribosylation and DNA damage response. LIFE SCIENCE ALLIANCE, 4(11).  Author URL.
Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Diaz RE, Young ID, Martins LC, Smith DH, Schulze-Gahmen U, et al (2021). Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking. SCIENCE ADVANCES, 7(16).  Author URL.
Rack JGM, Liu Q, Zorzini V, Voorneveld J, Ariza A, Ebrahimi KH, Reber JM, Krassnig SC, Ahel D, van der Marel GA, et al (2021). Mechanistic insights into the three steps of poly(ADP-ribosylation) reversal. NATURE COMMUNICATIONS, 12(1).  Author URL.
Gorbunova V, Buschbeck M, Cambronne XA, Chellappa K, Corda D, Du J, Freichel M, Gigas J, Green AE, Gu F, et al (2021). Meeting Report the 2021 FASEB science research conference on NAD metabolism and signaling. AGING-US, 13(23), 24924-24930.  Author URL.
Voorneveld J, Rack JGM, van Gijlswijk L, Meeuwenoord NJ, Liu Q, Overkleeft HS, van Der Marel GA, Ahel I, Filippov DV (2021). Molecular Tools for the Study of ADP-Ribosylation: a Unified and Versatile Method to Synthesise Native Mono-ADP-Ribosylated Peptides. CHEMISTRY-A EUROPEAN JOURNAL, 27(41), 10621-10627.  Author URL.
Kong L, Feng B, Yan Y, Zhang C, Kim JH, Xu L, Rack JGM, Wang Y, Jang J-C, Ahel I, et al (2021). Noncanonical mono(ADP-ribosyl)ation of zinc finger SZF proteins counteracts ubiquitination for protein homeostasis in plant immunity. MOLECULAR CELL, 81(22), 4591-+.  Author URL.
Gorbunova V, Buschbeck M, Cambronne XA, Chellappa K, Corda D, Du J, Freichel M, Gigas J, Green AE, Gu F, et al (2021). The 2021 FASEB science research conference on NAD metabolism and signaling. Aging, 13(23), 24924-24930.
Schuetzenhofer K, Rack JGM, Ahel I (2021). The Making and Breaking of Serine-ADP-Ribosylation in the DNA Damage Response. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 9  Author URL.
Rack JGM, Palazzo L, Ahel I (2020). (ADP-ribosyl)hydrolases: structure, function, and biology. GENES & DEVELOPMENT, 34(5-6), 263-284.  Author URL.
Rack JGM, Zorzini V, Zhu Z, Schuller M, Ahel D, Ahel I (2020). Viral macrodomains: a structural and evolutionary assessment of the pharmacological potential. OPEN BIOLOGY, 10(11).  Author URL.
Munnur D, Bartlett E, Mikolcevic P, Kirby IT, Rack JGM, Mikoc A, Cohen MS, Ahel I (2019). Reversible ADP-ribosylation of RNA. NUCLEIC ACIDS RESEARCH, 47(11), 5658-5669.  Author URL.
Rack JGM, Ariza A, Drown BS, Henfrey C, Bartlett E, Shirai T, Hergenrother PJ, Ahel I (2018). (ADP-ribosyl)hydrolases: Structural Basis for Differential Substrate Recognition and Inhibition. CELL CHEMICAL BIOLOGY, 25(12), 1533-+.  Author URL.
Drown BS, Shirai T, Rack JGM, Ahel I, Hergenrother PJ (2018). Monitoring Poly(ADP-ribosyl)glycohydrolase Activity with a Continuous Fluorescent Substrate. CELL CHEMICAL BIOLOGY, 25(12), 1562-+.  Author URL.
Voorneveld J, Rack JGM, Ahel I, Overkleeft HS, van der Marel GA, Filippov DV (2018). Synthetic α- and β-Ser-ADP-ribosylated Peptides Reveal α-Ser-ADPr as the Native Epimer. ORGANIC LETTERS, 20(13), 4140-4143.  Author URL.
Gibbs-Seymour I, Fontana P, Rack JGM, Ahel I (2016). HPF1/C4orf27 is a PARP-1-Interacting Protein that Regulates PARP-1 ADP-Ribosylation Activity. MOLECULAR CELL, 62(3), 432-442.  Author URL.
Rack JGM, Morra R, Barkauskaite E, Kraehenbuehl R, Ariza A, Qu Y, Ortmayer M, Leidecker O, Cameron DR, Matic I, et al (2015). Identification of a Class of Protein ADP-Ribosylating Sirtuins in Microbial Pathogens. MOLECULAR CELL, 59(2), 309-320.  Author URL.
Rack JGM, Lutter T, Kjæreng Bjerga GE, Guder C, Ehrhardt C, Värv S, Ziegler M, Aasland R (2015). The PHD finger of p300 influences its ability to acetylate histone and non-histone targets. Journal of Molecular Biology, 426(24), 3960-3972. Abstract.
Rack JGM, VanLinden MR, Lutter T, Aasland R, Ziegler M (2014). Constitutive Nuclear Localization of an Alternatively Spliced Sirtuin-2 Isoform. JOURNAL OF MOLECULAR BIOLOGY, 426(8), 1677-1691.  Author URL.
Dolle C, Rack JGM, Ziegler M (2013). NAD and ADP-ribose metabolism in mitochondria. FEBS JOURNAL, 280(15), 3530-3541.  Author URL.

Chapters

Rack JGM, Ahel I (2023). A Simple Method to Study ADP-Ribosylation Reversal: from Function to Drug Discovery. In  (Ed) Methods in Molecular Biology, 111-132. Abstract.
Rack JGM, Perina D, Ahel I (2016). Macrodomains: Structure, Function, Evolution, and Catalytic Activities. In  (Ed) ANNUAL REVIEW OF BIOCHEMISTRY, VOL 85, 431-454.  Author URL.

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