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O'Sullivan Lab


Roderick J. O'Sullivan, PhD

O'Sullivan Lab Website

The O’Sullivan lab at the Hillman Cancer Center conducts research into proteins that alter the structural and epigenetic functions of human telomeres. Telomeres are structures at the ends of chromosomes – the integrity of telomeres is an important factor in maintaining genome stability to prevent cancer and accelerated aging. Current efforts in the lab relate to deciphering the relationship between the regulation between chromatin structure and telomere function in the Alternative Lengthening of Telomeres pathway.

Headshot of Song-My  Hoang
Song-My Hoang
Graduate Student Researcher

Headshot of Michelle Lynskey
Michelle Lynskey
Graduate Student Researcher

Headshot of Roderick J. O'Sullivan, PhD
Roderick J. O'Sullivan, PhD
Associate Professor

Headshot of Anne Wondisford
Anne Wondisford
Graduate Student Researcher

Nicole Kaminski

Journal Articles

Prokhorova, E.; Agnew, T.; Wondisford, A.R.; Tellier, M.; Kaminski, N.; Beijer, D.; Holder, J.; Groslambert, J.; Suskiewicz, M.J.; Zhu, K.; Reber, J.M.; Krassnig, S.C.; Palazzo, L.; Murphy, S.; Nielsen, M.L.; Mangerich, A.; Ahel, D.; Baets, J.; O'Sullivan, R.J.; Ahel, I.Unrestrained poly-ADP-ribosylation provides insights into chromatin regulation and human disease. Molecular Cell. 17 June 2021;81(12):2640-2655.e8. doi: 10.1016/j.molcel.2021.04.028.
Evgeniia Prokhorova, Thomas Agnew, Anne R Wondisford, Michael Tellier, Nicole Kaminski, Danique Beijer, James Holder, Josephine Groslambert, Marcin J Suskiewicz, Kang Zhu, Julia M Reber, Sarah C Krassnig, Luca Palazzo, Shona Murphy, Michael L Nielsen, Aswin Mangerich, Dragana Ahel, Jonathan Baets, Roderick J O'Sullivan, Ivan Ahel. Unrestrained poly-ADP-ribosylation provides insights into chromatin regulation and human disease. Molecular Cell.2021 Jun 17;81(12):2640-2655.e8.
doi: 10.1016/j.molcel.2021.04.028. Epub 2021 May 20.
Kaminski, N.; Köster, C.; Mouloud, Y.; Börger, V.; Felderhoff-Müser, U.; Bendix, I.; Giebel, B.; Herz, J.Mesenchymal Stromal Cell-Derived Extracellular Vesicles Reduce Neuroinflammation, Promote Neural Cell Proliferation and Improve Oligodendrocyte Maturation in Neonatal Hypoxic-Ischemic Brain Injury. Frontiers in Cellular Neuroscience. 10 December 2020;14. doi: 10.3389/fncel.2020.601176.
Hoang, S.M.; Kaminski, N.; Bhargava, R.; Barroso-González, J.; Lynskey, M.L.; García-Expósito, L.; Roncaioli, J.L.; Wondisford, A.R.; Wallace, C.T.; Watkins, S.C.; James, D.I.; Waddell, I.D.; Ogilvie, D.; Smith, K.M.; da Veiga Leprevost, F.; Mellacharevu, D.; Nesvizhskii, A.I.; Li, J.; Ray-Gallet, D.; Sobol, R.W.; Almouzni, G.; O’Sullivan, R.J.Regulation of ALT-associated homology-directed repair by polyADP-ribosylation. Nature Structural and Molecular Biology. December 2020;27(12):1152-1164. doi: 10.1038/s41594-020-0512-7. 
Hoang SM, Kaminski N, Bhargava R, Barroso-González J, Lynskey ML, García-Expósito L, Roncaioli JL, Wondisford AR, Wallace CT, Watkins SC, James DI, Waddell ID, Ogilvie D, Smith KM, da Veiga Leprevost F, Mellacharevu D, Nesvizhskii AI, Li J, Ray-Gallet D, Sobol RW, Almouzni G, O'Sullivan RJ.  Regulation of ALT-associated homology-directed repair by polyADP-ribosylation. Nat Struct Mol Biol. 2020 Dec;27(12):1152-1164. doi: 10.1038/s41594-020-0512-7. Epub 2020 Oct 12. PMID: 33046907  PMCID: PMC7809635
 
Kaminski, N.A. and Wong, E.A. (2018) Differential mRNA expression of nutrient transporters in male and female chickens. Poultry Science, (97)1: 313–318, https://doi.org/10.3382/ps/pex262
 
Kaminski NA, Wong EA. Differential mRNA expression of nutrient transporters in male and female chickens. Poult Sci. 2018 Jan 1;97(1):313-318. doi: 10.3382/ps/pex262. PMID: 29077893.

Michelle Lynskey

Journal Articles

Longarini EJ, Dauben H, Locatelli C, Wondisford AR, Smith R, Muench C, Kolvenbach A, Lynskey ML, Pope A, Bonfiglio JJ, Jurado EP, Fajka-Boja R, Colby T, Schuller M, Ahel I, Timinszky G, O'Sullivan RJ, Huet S, Matic I. Modular antibodies reveal DNA damage-induced mono-ADP-ribosylation as a second wave of PARP1 signaling. Mol Cell. 2023 May 18;83(10):1743-1760.e11. doi: 10.1016/j.molcel.2023.03.027. Epub 2023 Apr 27. PMID: 37116497; PMCID: PMC10205078.
Bhargava R, Lynskey ML, O'Sullivan RJ. New twists to the ALTernative endings at telomeres. DNA Repair (Amst). 2022 Jul;115:103342. doi: 10.1016/j.dnarep.2022.103342. Epub 2022 May 13. PMID: 35588569; PMCID: PMC9675980.
Barroso-González J, García-Expósito L, Galaviz P, Lynskey ML, Allen JAM, Hoang S, Watkins SC, Pickett HA, O'Sullivan RJ. Anti-recombination function of MutSα restricts telomere extension by ALT-associated homology-directed repair. Cell Rep. 2021 Dec 7;37(10):110088. doi: 10.1016/j.celrep.2021.110088. PMID: 34879271; PMCID: PMC8724847
Hoang SM, Kaminski N, Bhargava R, Barroso-González J, Lynskey ML, García-Expósito L, Roncaioli JL, Wondisford AR, Wallace CT, Watkins SC, James DI, Waddell ID, Ogilvie D, Smith KM, da Veiga Leprevost F, Mellacharevu D, Nesvizhskii AI, Li J, Ray-Gallet D, Sobol RW, Almouzni G, O'Sullivan RJ.  Regulation of ALT-associated homology-directed repair by polyADP-ribosylation.  Nat Struct Mol Biol. 2020 Dec;27(12):1152-1164. doi: 10.1038/s41594-020-0512-7. Epub 2020 Oct 12. PMID: 33046907  PMCID: PMC7809635
 
Barroso-González J, García-Expósito L, Hoang SM, Lynskey ML, Roncaioli JL, Ghosh A, Wallace CT, Modesti M, Bernstein KA, Sarkar SN, Watkins SC, O'Sullivan RJ. RAD51AP1 Is an Essential Mediator of Alternative Lengthening of Telomeres. Mol Cell. 2019 Oct 3;76(1):217. doi: 10.1016/j.molcel.2019.08.009. Erratum for: Mol Cell. 2019 Oct 3;76(1):11-26.e7. PMID: 31585101; PMCID: PMC6823839
Barroso-González J, García-Expósito L, Hoang SM, Lynskey ML, Roncaioli JL, Ghosh A, Wallace CT, de Vitis M, Modesti M, Bernstein KA, Sarkar SN, Watkins SC, O'Sullivan RJ. RAD51AP1 Is an Essential Mediator of Alternative Lengthening of Telomeres. Mol Cell. 2020 Jul 16;79(2):359. doi: 10.1016/j.molcel.2020.06.026. Erratum for: Mol Cell. 2019 Oct 3;76(1):11-26.e7. PMID: 32679078; PMCID: PMC7439233.
Barroso-González J, García-Expósito L, Hoang SM, Lynskey ML, Roncaioli JL, Ghosh A, Wallace CT, de Vitis M, Modesti M, Bernstein KA, Sarkar SN, Watkins SC, O'Sullivan RJ.  RAD51AP1 Is an Essential Mediator of Alternative Lengthening of Telomeres.   Mol Cell. 2019 Oct 3;76(1):11-26.e7. doi: 10.1016/j.molcel.2019.06.043. Epub 2019 Aug 7. PMID: 31400850  PMCID: PMC6778027
 
Kaminski N, Wondisford AR, Kwon Y, Lynskey ML, Bhargava R, Barroso-González J, García-Expósito L, He B, Xu M, Mellacheruvu D, Watkins SC, Modesti M, Miller KM, Nesvizhskii AI, Zhang H, Sung P, O'Sullivan RJ. RAD51AP1 regulates ALT-HDR through chromatin-directed homeostasis of TERRA. Mol Cell. 2022 Nov 3;82(21):4001-4017.e7. doi: 10.1016/j.molcel.2022.09.025. Epub 2022 Oct 19. PMID: 36265488; PMCID: PMC9713952.

Roderick J. O'Sullivan, PhD

Journal Articles

O’Sullivan RJ, Arnoult N, Lackner DH, Oganesian L, Haggblom C, Corpet A, Almounzi G and Karlseder J. Rapid induction of the alternative lengthening of telomeres pathway by depletion of the histone chaperone ASF1. Nat Struct Mol Biol 21:167-174, 2013.
O’Sullivan R and Karlseder J. The great unravelling: Chromatin as a modulator of the aging process. Trends Biochem Sci 37:466-476, 2012.
Corpet A, De Koning L, Toedling J, Savignoni A, Berger F, Lemaitre C, O’Sullivan RJ, Karlseder J, Barrilot E, Asselain B, Sastre-Garau X and Almouzni G. Asf1b, the necessary Asf1 isoform for proliferation, is predictive of outcome in breast cancer. EMBO J 30:480-493, 2011.
Flynn RL, Centore RC, O’Sullivan RJ, Rai R, Tse A, Songyang Z, Chang S, Karlseder J and Zou L. TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature 471:532-526. 2011. 
O'Sullivan RJ and Karlseder J. Telomeres: protecting chromosomes against genome instability. Nat Rev Mol Cell Biol 11:171-81, 2010.
O’Sullivan RJ, Kubicek S, Schreiber SL and Karlseder J.  Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres. Nat Struct Mol Biol 17:1218-1226, 2010.
Kubicek S, O'Sullivan RJ, August EM, Hickey E, Mechtler K, Rea S, Farina P, Homon C, Kelly T and Jenuwein T. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 25:473-481, 2007.

Anne Wondisford

Journal Articles

Longarini EJ, Dauben H, Locatelli C, Wondisford AR, Smith R, Muench C, Kolvenbach A, Lynskey ML, Pope A, Bonfiglio JJ, Jurado EP, Fajka-Boja R, Colby T, Schuller M, Ahel I, Timinszky G, O'Sullivan RJ, Huet S, Matic I. Modular antibodies reveal DNA damage-induced mono-ADP-ribosylation as a second wave of PARP1 signaling. Mol Cell. 2023 May 18;83(10):1743-1760.e11. doi: 10.1016/j.molcel.2023.03.027. Epub 2023 Apr 27. PMID: 37116497; PMCID: PMC10205078.
Kaminski N, Wondisford AR, Known Y, Lynskey M, , Bhargava R, Barrosso-Gonzalez J, Garcia- Exposito L, He B, Xu M, Mellaharevu D, Watkins S, Modesti M, Nesvizhskii A, Zhang H, Sung P and O’Sullivan RJ. RAD51AP1 regulates ALT-HDR through chromatin-directed homeostasis of TERRA. Mol Cell. 2022. https://doi.org/10.1016/j.molcel.2022.09.025
 
Prokhorova E, Agnew T, Wondisford AR, Tellier M, Kaminski N, Beijer D, Holder J, Groslambert J, Suskiewicz MJ, Zhu K, Reber JM, Krassnig SC, Palazzo L, Murphy S, Nielsen ML, Mangerich A, Ahel D, Baets J, O'Sullivan RJ, Ahel I. Unrestrained poly-ADP-ribosylation provides insights into chromatin regulation and human disease. Mol Cell. 2021 Jun 17;81(12):2640-2655.e8. doi: 10.1016/j.molcel.2021.04.028. PMID: 34019811; PMCID: PMC8221567.
Hoang SM, Kaminski N, Bhargava R, Barroso-González J, Lynskey ML, García-Expósito L, Roncaioli JL, Wondisford AR, Wallace CT, Watkins SC, James DI, Waddell ID, Ogilvie D, Smith KM, da Veiga Leprevost F, Mellacharevu D, Nesvizhskii AI, Li J, Ray-Gallet D, Sobol RW, Almouzni G, O'Sullivan RJ. Regulation of ALT-associated homology-directed repair by polyADP-ribosylation. Nat Struct Mol Biol. 2020 Oct 12. doi: 10.1038/s41594-020-0512-7. PMID: 33046907 PMCID: PMC7809635