Fondufe-Mittendorf Laboratory

OVERVIEW

Epigenetic Regulation and Environmental Impacts

The Fondufe-Mittendorf Lab focuses on mechanisms by which chromatin and the epigenome are modulated during normal growth and in response to environmental cues. Our lab uses multifaceted approaches at the interface of biology, toxicology, bioinformatics and medicine to study how and when the modulation of chromatin and epigenomics goes awry, leading to changes in gene expression that drives disease pathology. Our findings will not only provide a basic mechanistic insight into principles that govern gene regulation but also will inform on gene expression dysregulation in disease pathology and ultimately drug discovery.

We're hiring!

The Fondufe-Mittendorf Lab is hiring! We are seeking postdoctoral fellows who will carry out a project to explore how chromatin structure regulates epigenetic and epitranscriptomic machinery in response to normal growth and environmental cues.

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  • 88 studies published from Jan. 1, 2022 to Sept. 21, 2022
  • 44 studies in high-impact journals from Jan. 1, 2022 to Sept. 21, 2022
  • 42 clinical trials launched

Yvonne Fondufe-Mittendorf, Ph.D.

Professor, Department of Epigenetics

Areas of Expertise

Epigenetics, chromatin biology, environmental impacts, cancer, nucleosome structure, toxicology, disease pathology, bioinformatics

Biography

Dr. Yvonne Fondufe-Mittendorf is an epigenetics expert with an interest in how environmental factors impact the epigenome and spur cancer development. She earned her bachelor’s and master’s degrees from University of Ibadan, Nigeria, and her Ph.D. in molecular genetics from Georg-August Universitaet, Germany. Following postdoctoral fellowships in the Jovin Lab at Max Planck Institute for Biophysical Chemistry, Germany, and the Widom Lab at Northwestern University, Dr. Fondufe-Mittendorf joined University of Kentucky as an assistant professor. She was promoted to full professor in 2021. She joined Van Andel Institute’s Department of Epigenetics as a professor in 2022. Her research blends epigenetics, toxicology, bioinformatics and medicine to understand how interactions with the environment, such as exposure to toxicants like arsenic, drive gene dysregulation and disease pathology. She and her groundbreaking research have been highlighted by American Society for Biochemistry and Molecular Biology, PLoS One Everyone, Onclive and the National Institute of Environmental Health Sciences’ Environmental Factor. She has earned multiple awards for her research and mentorship, including the National Institute of Health’s IDeA Thomas Maciag Award, University of Kentucky Research Professorship and recognition from University of Kentucky’s Chellgreen Center.

Professional Memberships

  • American Society of Biochemistry and Molecular Biology
  • Biophysical Society
  • Epigenetics Society
  • Society of Toxicology
  • Epigenetics and Mutagenesis Society
  • Editorial board, Scientific Reports

SELECTED PUBLICATIONS

View Dr. Fondufe-Mittendorf’s NCBI bibliography here.

Saintilnord WN, Tenlep SYN, Preston JD, Duregon E, DeRouchey JE, Unrine JM, de Cabo R, Pearson KJ, Fondufe-Mittendorf YN. 2021. Chronic exposure to cadmium induces differential methylation in mice spermatozoaTox Sci 180(2):262–276.

Leachman J, Rea M, Cohn D, Xiu X, Dalmasso C, Fondufe-Mittendorf YN, Loria A. 2020. Mice exposed to early life stress display sex-specific upregulation of leptin gene expression in adipose tissueAm J Physiol Endocrinol Metab 319(5):E852–E862.

Rebekah E, Fondufe-Mittendorf YN. 2020. The multifaceted role of PARP1 in RNA biogenesisWIRES RNA.

von Walden F, Rea M, Mobley CB, Fondufe-Mittendorf YN, McCarthy JJ, Peterson CA, Murach KA. 2020. The myonuclear DNA methylome in response to an acute hypertrophic stimulusEpigenetics 15(11):1151–1162.

Zhang C, Fondufe-Mittendorf YN, Wang C, Chen J, Cheng Q, Zhou D, Zheng Y, Geiger H, Liang Y. 2019. Latexin regulation by HMGB2 is required for hematopoietic stem cell maintenanceHaematologica 105(3).

Convertini P, Todisco S, De Santis F, Pappalardo I, Iacobazzi D, Castiglione Morelli MA, Fondufe-Mittendorf YN, Martelli G, Palmieri F, Infantino V. 2019. Transcriptional regulation factors of the human mitochondrial aspartate/glutamate carrier gene, isoform 2 (SLC25A13): USF1 as basal factor and FOXA2 as activator in liver cellsInt J Mol Sci 20(8):1888.

Matveeva EA, Mathbout LF, Fondufe-Mittendorf YN. 2019. PARP1 is a versatile factor in the regulation of mRNA stability and decaySci Rep 9:3722.

Matveeva EA, Al-Tinawi QMH, Rouchka EC, Fondufe-Mittendorf YN. 2019. Coupling of PARP1-mediated chromatin structural changes to transcriptional RNA polymerase II elongation and cotranscriptional splicingEpigenetics Chromatin 12(1):15.

Melikishvili M, Charliker J, Rouchka E, Fondufe-Mittendorf YN. 2017. Transcriptome-wide Identification of the RNA-binding profile of the chromatin-associated protein PARP1, reveals functions in RNA biogenesisNat Cell Disc 3:17043.

Rea M, Gripshover T, Fondufe-Mittendorf YN. 2017. Selective Inhibition of CTCF binding by iAs directs TET-mediated reprogramming of 5-hydroxymethylation patterns in iAs transformed cells. Toxicol Appl Pharmacol 338:124–133.

Melikishvili M, Matveeva E, Fondufe-Mittendorf YN. 2017. Methodology to identify Poly-ADPRibose Polymerase 1 (PARP1)-mRNA targets by PAR-CLiPMethods Mol. Biol 1608:211–228.

Eckstein M, Rea M, Fondufe-Mittendorf YN. 2017. Microarray dataset of transient and permanent DNA methylation changes in HeLa cells undergoing inorganic arsenic-mediated epithelial-to-mesenchymal transitionData Brief 13:6–9.

Martin RL, Maiorano J, Beitel GJ, Marko JF, McVicker G, Fondufe-Mittendorf YN. 2017. A comparison of nucleosome organization in Drosophila cell linesPLoS One 12(6):e0178590.

Eckstein M, Eleazer R, Rea M, Fondufe-Mittendorf YN. 2017. Transient and permanent changes in DNA methylation patterns in inorganic arsenic-mediated epithelial-to-mesenchymal transitionToxicol Appl Pharmacol 331:6–17.

Eckstein M, Eleazer R, Rea M, Fondufe-Mittendorf YN. 2017. Epigenomic reprogramming in inorganic arsenic-mediated gene expression patterns during carcinogenesisRev Enviro Health 32(1-2):93–103.

Rea M, Eckstein M, Eleazer R*, Smith C*, Fondufe-Mittendorf YN, 2017. Genome-wide DNA methylation reprogramming in response to inorganic arsenic links inhibition of CTCF binding, DNMT expression and cellular transformationSci Rep 7:41474.

Riedmann C, Fondufe-Mittendorf YN. 2016. Comparative analysis of linker histone H1, MeCP2, and HMGD1 on nucleosome stability and target site accessibilitySci Rep 6:33186.

Rea M, Jiang T, Eleazer R, Eckstein M, Marshall AG, Fondufe-Mittendorf YN. 2016. Quantitative mass spectrometry reveals changes in Histone H2B variants as cells undergo inorganic arsenic-mediated cellular transformationMol Cell Proteo 15(7): 2411–2422.

Matveeva E, Maiorano J, Zhang Q, Eteleeb A, Convertini P, Chen Jing, Stamm S, Rouchka EC, Wang J and Fondufe-Mittendorf YN. 2016. A role of PARP1 in alternative splicing regulationCell Disc 2:15046.

Bernier M, Nwokelo KC, Luo Y, Dreher SJ, Fondufe-Mittendorf YN, Ottesen JJ, Poirier MG. 2015. Linker Histone H1.0 and H3K56 acetylation are antagonistic regulators of nucleosome dynamicsNat Commun 6:10152.

Nalabothula N, Al-jumaily T, Shao X, Abdallah, E, Flight R, Hunter M, Rouchka, E, Fondufe-Mittendorf YN. 2015. Genome-wide profiling of PARP-1 reveals an interplay with gene regulatory regions and DNA methylationPLoS One 10(8):e0135410).

Riedmann C, Ma Y, Melikishvili M, Godfrey SG, Zhang Z, Chen KC, Rouchka EC, Fondufe-Mittendorf YN. 2015. Inorganic arsenic-induced cellular transformation is coupled with genome wide changes in chromatin structure, transcriptome and splicing patternsBMC Genomics 16:212.

Convertini P, Shen M, Potter P, Palacios G, Lagisetti C, de la Grange P, Horbinski C, Fondufe-Mittendorf YN, Webb T, Stamm S. 2014. Sudemycin E influences alternative splicing and changes chromatin modificationsNuc Acids Res 42(8): 4947–4961.

Nalabothula, N, McVicker G, Maiorano J, Martin R, Pritchard JK, Fondufe-Mittendorf YN. 2014. The chromatin architectural proteins HMGD1 and H1 bind reciprocally and have opposite effects on chromatin structure and gene regulationBMC Genomics 15(1):92.

Nalabothula N, Xi L, Bhattacharyya S, Widom J, Wang JP, Reeve JN, Santangelo TJ, Fondufe-Mittendorf YN. 2013. Archaeal nucleosome positioning in vivo and in vitro is directed by primary sequence motifsBMC Genomics 14:391.
*Highlighted in F1000

Gaffney DJ, McVicker G, Pai AA, Fondufe-Mittendorf YN, Lewellen N, Michelini K, Widom J, Gilad Y, Pritchard JK. 2012. Controls of nucleosome positioning in the human genomePLoS Genet 8(11):e1003036.

Kaplan N, Moore I, Fondufe-Mittendorf YN, Gossett AJ, Tillo D, Field Y, Hughes TR, Lieb JD, Widom J, Segal E. 2010. Nucleosome sequence preferences influence in vivo nucleosome organizationNat Struct Mol Biol 17(8):918–920.

Xi L, Fondufe-Mittendorf YN, Xia L, Flatow J, Widom J, Wang JP. 2010. Predicting nucleosome positioning using a duration Hidden Markov ModelBMC Bioinformatics 11:346.

Tillo D, Kaplan N, Moore I, Fondufe-Mittendorf YN, Gossett AJ, Field Y, Lieb JD, Widom J, Segal E, Hughes TR. 2010. Human regulatory sequences have high intrinsic nucleosome occupancyPLoS ONE 5(2):e9129.

Field Y*, Fondufe-Mittendorf YN*, Moore I, Mieczkowski P, Kaplan N, Lieb J, Widom J, Segal E. 2009. Gene expression reprogramming in yeast coupled to evolution of DNA-encoded nucleosome organizationNat Genet 41(4):438–445.
*Equal contributions

Kaplan N*, Moore I*, Fondufe-Mittendorf YN, Gossett A, Tillo D, Field Y, LeProust EM, Hughes TR, Lieb JD, Widom J, Segal E. 2009. DNA – encoded nucleosome organization of a eukaryotic genomeNature 458(7236):362–366).
*Equal contributions

Field Y*, Kaplan N*, Fondufe-Mittendorf YN*, Moore IK, Sharon E, Lubling Y, Widom J, Segal E. 2008. Different types of transcriptional programs encoded by nucleosome positioning signalsPLoS Comput Biol 4(11): e1000216.
*Equal contributions

Wang JP, Fondufe-Mittendorf YN, Tsai GF, Xi L, Segal E, Widom J. 2008. Preferentially quantized linker DNA lengths in Saccharomyces cerevisiaePLoS Comput Biol 4(9):e1000175.

Brickner, DG, Cjigas I, Fondufe-Mittendorf YN, Ahmed S, Lee PC, Widom J, Brickner J. 2007. H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional statePLoS Biol Apr 5(4):e81.

Segal, E Fondufe-Mittendorf YN, Chen L, Thåström AC, Field Y, Moore IK, Wang JPZ, Widom J. 2006. A genomic code for nucleosome positioning. Nature 442(7104):772–778.
*Featured in the New York Times, Nature cover, Nature News & Views, and Nature Reviews Genetics. Top ranked paper in all of biology on Faculty of 1000 review. Highlighted in Nature News Feature, (2006) 244: 259-261, and again in Nature/Nurture (Autumn, 2006) as top-most downloaded research paper from Nature over current four-month period.

Fondufe-Mittendorf YN, Harer C, Kramer W, Fritz HJ. 2002. Two amino acid replacements change the substrate preference of DNA mismatch glycosylase Mig.MthI from T/G to A/GNucleic Acids Res 30(2):614–621.

Fondufe-Mittendorf YN. 2000. Characterization and directed modification of the substrate selectivity of Mig.Mth, a DNA repair glycosylase from the thermophilic archaeon Methanobacterium thermoautotrophicum. ISBN 3-89712-969-8 Cuvillier Verlag.

Richard Cassidy

Van Andel Institute Graduate School Student

Thesis project title to be determined

Hejer Dhahri

University of Kentucky Graduate Student

Rebekah Eleazer

University of Kentucky Graduate Student

Investigates the cicrRNA biogenesis and their function in arsenic-carcinogenesis.

Smitha George

Smitha George, Ph.D.

Postdoctoral Fellow, Fondufe-Mittendorf Laboratory

Manana Melikishvili, Ph.D.

Research Scientist, Department of Epigenetics

Amy Nuffesse

Senior Administrative Assistant II, Department of Epigenetics

Nour El Osmani, Ph.D.

Postdoctoral Fellow, Fondufe-Mittendorf Laboratory

Matthew Rea, Ph.D.

Research Scientist, Department of Epigenetics

Wesley Saintilnord

University of Kentucky Graduate Student