Karen Usdin, Ph.D.

Acting Chief: Laboratory of Cell & Molecular Biology
Section Chief: Gene Structure and Disease Section, Laboratory of Cell & Molecular Biology

Scientific Focus Areas: Genetics and Genomics, Stem Cell Biology, Molecular Biology and Biochemistry, RNA Biology, Chromosome Biology

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Publications

A selection of recent and significant publications can be viewed below.

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The fragile X locus is prone to spontaneous DNA damage that is preferentially repaired by nonhomologous end-joining to preserve genome integrity.: Kumari D, Lokanga RA, McCann C, Ried T, Usdin K.; iScience (2024 Feb 16) 27:108814. Abstract/Full Text
Both cis and trans-acting genetic factors drive somatic instability in female carriers of the FMR1 premutation.: Hwang YH, Hayward BE, Zafarullah M, Kumar J, Durbin Johnson B, Holmans P, Usdin K, Tassone F.; Sci Rep (2022 Jun 21) 12:10419. Abstract/Full Text
All three MutL complexes are required for repeat expansion in a human stem cell model of CAG-repeat expansion mediated glutaminase deficiency.: Hayward B, Kumari D, Santra S, van Karnebeek CDM, van Kuilenburg ABP, Usdin K.; Sci Rep (2024 Jun 14) 14:13772. Abstract/Full Text
FAN1's protection against CGG repeat expansion requires its nuclease activity and is FANCD2-independent.: Zhao X, Lu H, Usdin K.; Nucleic Acids Res (2021 Nov 18) 49:11643-11652. Abstract/Full Text
Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS.: van Kuilenburg ABP, Tarailo-Graovac M, Richmond PA, Drögemöller BI, Pouladi MA, Leen R, Brand-Arzamendi K, Dobritzsch D, Dolzhenko E, Eberle MA, Hayward B, Jones MJ, Karbassi F, Kobor MS, Koster J, Kumari D, Li M, MacIsaac J, McDonald C, Meijer J, Nguyen C, Rajan-Babu IS, Scherer SW, Sim B, Trost B, Tseng LA, Turkenburg M, van Vugt JJFA, Veldink JH, Walia JS, Wang Y, van Weeghel M, Wright GEB, Xu X, Yuen RKC, Zhang J, Ross CJ, Wasserman WW, Geraghty MT, Santra S, Wanders RJA, Wen XY, Waterham HR, Usdin K, van Karnebeek CDM.; N Engl J Med (2019 Apr 11) 380:1433-1441. Abstract/Full Text

Additional Publications

Repeat expansions nested within tandem CNVs: a unique structural change in GLS exemplifies the diagnostic challenges of non-coding pathogenic variation.: Fazal S, Danzi MC, van Kuilenburg ABP, Reich S, Traschütz A, Bender B, Leen R, Toro C, Usdin K, Hayward B, Adams DR, van Karnebeek CDM, Ferreira CR, D'Sousa P, Network UD, Tekin M, Züchner S, Synofzik M.; Hum Mol Genet (2023 Jan 1) 32:46-54. Abstract/Full Text
S1-END-seq reveals DNA secondary structures in human cells.: Matos-Rodrigues G, van Wietmarschen N, Wu W, Tripathi V, Koussa NC, Pavani R, Nathan WJ, Callen E, Belinky F, Mohammed A, Napierala M, Usdin K, Ansari AZ, Mirkin SM, Nussenzweig A.; Mol Cell (2022 Oct 6) 82:3538-3552.e5. Abstract/Full Text
Mismatch repair is a double-edged sword in the battle against microsatellite instability.: Miller CJ, Usdin K.; Expert Rev Mol Med (2022 Sep 5) 24:e32. Abstract/Full Text
Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models.: Zhao X, McHugh C, Coffey SR, Jimenez DA, Adams E, Carroll JB, Usdin K.; Dis Model Mech (2022 May 1) 15. Abstract/Full Text
Mechanisms of Genome Instability in the Fragile X-Related Disorders.: Hayward BE, Usdin K.; Genes (Basel) (2021 Oct 17) 12. Abstract/Full Text
Common Threads: Aphidicolin-Inducible and Folate-Sensitive Fragile Sites in the Human Genome.: Lokanga RA, Kumari D, Usdin K.; Front Genet (2021) 12:708860. Abstract/Full Text
(Dys)function Follows Form: Nucleic Acid Structure, Repeat Expansion, and Disease Pathology in FMR1 Disorders.: Zhao X, Usdin K.; Int J Mol Sci (2021 Aug 25) 22. Abstract/Full Text
Modifiers of Somatic Repeat Instability in Mouse Models of Friedreich Ataxia and the Fragile X-Related Disorders: Implications for the Mechanism of Somatic Expansion in Huntington's Disease.: Zhao X, Kumari D, Miller CJ, Kim GY, Hayward B, Vitalo AG, Pinto RM, Usdin K.; J Huntingtons Dis (2021) 10:149-163. Abstract/Full Text
Repeat expansions confer WRN dependence in microsatellite-unstable cancers.: van Wietmarschen N, Sridharan S, Nathan WJ, Tubbs A, Chan EM, Callen E, Wu W, Belinky F, Tripathi V, Wong N, Foster K, Noorbakhsh J, Garimella K, Cruz-Migoni A, Sommers JA, Huang Y, Borah AA, Smith JT, Kalfon J, Kesten N, Fugger K, Walker RL, Dolzhenko E, Eberle MA, Hayward BE, Usdin K, Freudenreich CH, Brosh RM Jr, West SC, McHugh PJ, Meltzer PS, Bass AJ, Nussenzweig A.; Nature (2020 Oct) 586:292-298. Abstract/Full Text
CGG Repeat Expansion, and Elevated Fmr1 Transcription and Mitochondrial Copy Number in a New Fragile X PM Mouse Embryonic Stem Cell Model.: Gazy I, Miller CJ, Kim GY, Usdin K.; Front Cell Dev Biol (2020) 8:482. Abstract/Full Text
Small Molecules Targeting H3K9 Methylation Prevent Silencing of Reactivated FMR1 Alleles in Fragile X Syndrome Patient Derived Cells.: Kumari D, Sciascia N, Usdin K.; Genes (Basel) (2020 Mar 27) 11. Abstract/Full Text
Fragile X syndrome in a male with methylated premutation alleles and no detectable methylated full mutation alleles.: Hayward B, Loutaev I, Ding X, Nolin SL, Thurm A, Usdin K, Smith CB.; Am J Med Genet A (2019 Oct) 179:2132-2137. Abstract/Full Text
Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS. Reply.: van Kuilenburg ABP, Usdin K, van Karnebeek CDM.; N Engl J Med (2019 Sep 19) 381:1185. Abstract/Full Text
Pharmacological Reactivation of the Silenced FMR1 Gene as a Targeted Therapeutic Approach for Fragile X Syndrome.: Kumari D, Gazy I, Usdin K.; Brain Sci (2019 Feb 12) 9. Abstract/Full Text
Double-strand break repair plays a role in repeat instability in a fragile X mouse model.: Gazy I, Hayward B, Potapova S, Zhao X, Usdin K.; DNA Repair (Amst) (2019 Feb) 74:63-69. Abstract/Full Text
Assays for Determining Repeat Number, Methylation Status, and AGG Interruptions in the Fragile X-Related Disorders.: Hayward BE, Usdin K.; Methods Mol Biol (2019) 1942:49-59. Abstract/Full Text
MutLγ promotes repeat expansion in a Fragile X mouse model while EXO1 is protective.: Zhao X, Zhang Y, Wilkins K, Edelmann W, Usdin K.; PLoS Genet (2018 Oct) 14:e1007719. Abstract/Full Text
FAN1 protects against repeat expansions in a Fragile X mouse model.: Zhao XN, Usdin K.; DNA Repair (Amst) (2018 Sep) 69:1-5. Abstract/Full Text
Timing of Expansion of Fragile X Premutation Alleles During Intergenerational Transmission in a Mouse Model of the Fragile X-Related Disorders.: Zhao XN, Usdin K.; Front Genet (2018) 9:314. Abstract/Full Text
Improved Assays for AGG Interruptions in Fragile X Premutation Carriers.: Hayward BE, Usdin K.; J Mol Diagn (2017 Nov) 19:828-835. Abstract/Full Text
Recent advances in assays for the fragile X-related disorders.: Hayward BE, Kumari D, Usdin K.; Hum Genet (2017 Oct) 136:1313-1327. Abstract/Full Text
CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons.: Zhou Y, Kumari D, Sciascia N, Usdin K.; Mol Autism (2016) 7:42. Abstract/Full Text
Ups and Downs: Mechanisms of Repeat Instability in the Fragile X-Related Disorders.: Zhao XN, Usdin K.; Genes (Basel) (2016 Sep 21) 7. Abstract/Full Text
Sustained expression of FMR1 mRNA from reactivated fragile X syndrome alleles after treatment with small molecules that prevent trimethylation of H3K27.: Kumari D, Usdin K.; Hum Mol Genet (2016 Sep 1) 25:3689-3698. Abstract/Full Text
A Set of Assays for the Comprehensive Analysis of FMR1 Alleles in the Fragile X-Related Disorders.: Hayward BE, Zhou Y, Kumari D, Usdin K.; J Mol Diagn (2016 Sep) 18:762-774. Abstract/Full Text
A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice?: Zhao XN, Lokanga R, Allette K, Gazy I, Wu D, Usdin K.; PLoS Genet (2016 Jul) 12:e1006190. Abstract/Full Text
Granulosa cell and oocyte mitochondrial abnormalities in a mouse model of fragile X primary ovarian insufficiency.: Conca Dioguardi C, Uslu B, Haynes M, Kurus M, Gul M, Miao DQ, De Santis L, Ferrari M, Bellone S, Santin A, Giulivi C, Hoffman G, Usdin K, Johnson J.; Mol Hum Reprod (2016 Jun) 22:384-96. Abstract/Full Text
Mutsβ generates both expansions and contractions in a mouse model of the Fragile X-associated disorders.: Zhao XN, Kumari D, Gupta S, Wu D, Evanitsky M, Yang W, Usdin K.; Hum Mol Genet (2015 Dec 15) 24:7087-96. Abstract/Full Text
Evidence for chromosome fragility at the frataxin locus in Friedreich ataxia.: Kumari D, Hayward B, Nakamura AJ, Bonner WM, Usdin K.; Mutat Res (2015 Nov) 781:14-21. Abstract/Full Text
The Repeat Expansion Diseases: The dark side of DNA repair.: Zhao XN, Usdin K.; DNA Repair (Amst) (2015 Aug) 32:96-105. Abstract/Full Text
High-Throughput Screening to Identify Compounds That Increase Fragile X Mental Retardation Protein Expression in Neural Stem Cells Differentiated From Fragile X Syndrome Patient-Derived Induced Pluripotent Stem Cells.: Kumari D, Swaroop M, Southall N, Huang W, Zheng W, Usdin K.; Stem Cells Transl Med (2015 Jul) 4:800-8. Abstract/Full Text
Repeat-mediated epigenetic dysregulation of the FMR1 gene in the fragile X-related disorders.: Usdin K, Kumari D.; Front Genet (2015) 6:192. Abstract/Full Text
Heterozygosity for a hypomorphic Polβ mutation reduces the expansion frequency in a mouse model of the Fragile X-related disorders.: Lokanga RA, Senejani AG, Sweasy JB, Usdin K.; PLoS Genet (2015 Apr) 11:e1005181. Abstract/Full Text
The transcription-coupled repair protein ERCC6/CSB also protects against repeat expansion in a mouse model of the fragile X premutation.: Zhao XN, Usdin K.; Hum Mutat (2015 Apr) 36:482-7. Abstract/Full Text
Repeat instability during DNA repair: Insights from model systems.: Usdin K, House NC, Freudenreich CH.; Crit Rev Biochem Mol Biol (2015 Mar-Apr) 50:142-67. Abstract/Full Text
Polycomb group complexes are recruited to reactivated FMR1 alleles in Fragile X syndrome in response to FMR1 transcription.: Kumari D, Usdin K.; Hum Mol Genet (2014 Dec 15) 23:6575-83. Abstract/Full Text
Identification of fragile X syndrome specific molecular markers in human fibroblasts: a useful model to test the efficacy of therapeutic drugs.: Kumari D, Bhattacharya A, Nadel J, Moulton K, Zeak NM, Glicksman A, Dobkin C, Brick DJ, Schwartz PH, Smith CB, Klann E, Usdin K.; Hum Mutat (2014 Dec) 35:1485-94. Abstract/Full Text
X inactivation plays a major role in the gender bias in somatic expansion in a mouse model of the fragile X-related disorders: implications for the mechanism of repeat expansion.: Adihe Lokanga R, Zhao XN, Entezam A, Usdin K.; Hum Mol Genet (2014 Sep 15) 23:4985-94. Abstract/Full Text
Repeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders.: Usdin K, Hayward BE, Kumari D, Lokanga RA, Sciascia N, Zhao XN.; Front Genet (2014) 5:226. Abstract/Full Text
Chromosome fragility and the abnormal replication of the FMR1 locus in fragile X syndrome.: Yudkin D, Hayward BE, Aladjem MI, Kumari D, Usdin K.; Hum Mol Genet (2014 Jun 1) 23:2940-52. Abstract/Full Text
The mismatch repair protein MSH2 is rate limiting for repeat expansion in a fragile X premutation mouse model.: Lokanga RA, Zhao XN, Usdin K.; Hum Mutat (2014 Jan) 35:129-36. Abstract/Full Text
Mouse models of the fragile X premutation and fragile X-associated tremor/ataxia syndrome.: Berman RF, Buijsen RA, Usdin K, Pintado E, Kooy F, Pretto D, Pessah IN, Nelson DL, Zalewski Z, Charlet-Bergeurand N, Willemsen R, Hukema RK.; J Neurodev Disord (2014) 6:25. Abstract/Full Text
Use of model systems to understand the etiology of fragile X-associated primary ovarian insufficiency (FXPOI).: Sherman SL, Curnow EC, Easley CA, Jin P, Hukema RK, Tejada MI, Willemsen R, Usdin K.; J Neurodev Disord (2014) 6:26. Abstract/Full Text
Somatic expansion in mouse and human carriers of fragile X premutation alleles.: Lokanga RA, Entezam A, Kumari D, Yudkin D, Qin M, Smith CB, Usdin K.; Hum Mutat (2013 Jan) 34:157-66. Abstract/Full Text
Repeat expansion affects both transcription initiation and elongation in friedreich ataxia cells.: Kumari D, Biacsi RE, Usdin K.; J Biol Chem (2011 Feb 11) 286:4209-15. Abstract/Full Text

Last Reviewed March 2025