Research at the Integrity of the Genome and Oncology Laboratory focuses on DNA damage and repair, translated to cancer prevention.

TEAM

DIRECTOR​
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Pierre-Alexandre Vidi, PhD
POSTDOCS
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Maëlle Locatelli, PhD (@Wake)
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Amine Maarouf, PhD
GRADUATE STUDENTS 
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Mohamed Gaber (@Wake)
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Sarvath ​Sanaullah (@Wake)
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Marie Robert, MD
LABORATORY TECHNICIAN
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Cassandra Lepetit
UNDERGRADUATE STUDENTS
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Cloé Dehours (Polytech Angers)
OPEN POSITIONS
Projects for master students are available.

RESEARCH

The InGenO laboratory has three research themes:

  1. Impact of the cell microenvironment on the DNA damage response. Obesity and high mammographic density both elevate breast cancer risk and are characterized by profound changes in the extracellular matrix (ECM). Stiffening of the ECM is also a hallmark of the initiation of hepatocarcinoma. What are the molecular connections between drifts in the chemical nature and physical properties of the cell microenvironment and genome maintenance?

    We address these questions using 3D cell culture models and human tissues. This fundamental knowledge is needed to advance primary prevention.
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  2. Chromatin motions and DNA repair. How is chromatin dynamics changing in response to DNA damage, and what are the functional consequences of DNA motions for DNA repair outcomes?

    We use live cell microscopy to test the hypothesis that chromatin motions are necessary for the biogenesis of genomic translocations, which are major drivers of secondary cancers. The translational goal is to predict (and possibly prevent) genomic rearrangements in cells with multiple DNA breaks caused by chemotherapeutics. This project is part of the NCI's Physical Sciences - Oncology Network (PS-ON). 

  3. Genotoxicity of environmental pollutants. Children are exposed to pesticides and other toxic chemicals in their environment. What are the consequences of these expositions for their health? 
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    ​We combine pesticide exposure data with DNA damage detection in plucked hair follicles – a molecular marker of risk for cancer and other diseases. Understanding which pesticides (or pesticide mixtures) lead to genotoxic effects is essential for policymaking in environmental health.​
InGenO’s research spans single cell analyses to community-based participatory research.

TECHNOLOGY

​The InGenO laboratory collaborates with physicists and chemists to develop biocompatible dyes and innovative imaging setups, among other resources. Here are a few examples.
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Miniature X-ray system to induce DNA damage during live cell imaging. Collaboration with Surendra Prajapati and Paul Black.
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Diffractive optics module to generate structured illumination patterns (here, of photoactivated chromatin microdomains). Collaboration with Keith Bonin and George Holzwarth.
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High-content 3D cell culture and automated analysis of acinar differentiation. Collaboration with Keith Bonin.

PUBLICATIONS

Selected publications, relevant to current research in the InGenO laboratory, are listed below.
All publications: PubMed

Theme 1 | Molecular characterization of cancer risk
  1. Interconnected contribution of tissue morphogenesis and the nuclear protein NuMA to the DNA damage response. 
    Vidi PA@, Chandramouly G, Gray M, Wang L, Liu E, Kim JJ, Roukos V, Bissell MJ, Moghe PV, Lelievre SA@.  
    Journal of Cell Science. 2012 125(Pt 2):350-361. [link]
    Discovery that cell-ECM interactions regulate the DNA damage response, with implication of a nuclear structural protein

  2. NuMA promotes homologous recombination repair by regulating the accumulation of the ISWI ATPase SNF2h at DNA breaks. 
    Vidi PA@, Liu J, Salles D, Jayaraman S, Dorfman G, Gray M, Abad P, Moghe PV, Irudayaraj JM, Wiesmuller L, Lelievre SA@. 
    Nucleic Acids Research. 2014 42(10):6365-6379. [link]

  3. High-content image informatics of the structural nuclear protein NuMA parses trajectories for stem/progenitor cell lineages and oncogenic transformation.
    Vega SL, Liu E, Arvind V, Bushman J, Sung HJ, Becker ML, Lelièvre S, Kohn J, Vidi PA@, Moghe PV@.
    Exp Cell Res. 2017 351(1):11-23.

  4. The nuclear structural protein NuMA is a negative regulator of 53BP1 in DNA double-strand break repair. 
    Salvador Moreno N, Liu J, Haas KM, Parker LL, Chakraborty C, Kron SJ, Hodges K, Miller LD, Robinson PL, Lelièvre SA, and Vidi PA@.  
    Nucleic Acids Research. 2019 47(6):2703-2715. [link]
    These publications define a novel role for NuMA in DNA repair. 

  5. Loss of XIST in Breast Cancer Activates MSN-c-Met and Reprograms Microglia via Exosomal miRNA to Promote Brain Metastasis.
    Xing F, Liu Y, Wu SY, Wu K, Sharma S, Mo YY, Feng J, Sanders S, Jin G, Singh R, Vidi PA, Tyagi A, Chan MD, Ruiz J, Debinski W, Pasche BC, Lo HW, Metheny-Barlow LJ, D'Agostino RB Jr, Watabe K@.
    Cancer Res. 2018 78(15):4316-4330.

  6. Elevated leptin disrupts epithelial polarity and primes cancer initiation in the mammary gland.
    Tenvooren I, Jenks MZ, Rashid H, Cook KL, Muhlemann JK, Sistrunk C, Holmes J, Wang K, Bonin K, Hodges K, Lo HW, Shaikh A, Camarillo IG, Lelièvre SA, Seewaldt V, Vidi PA@.
    Oncogene. 2019 38(20):3855-3870

  7. Connexin 43 maintains tissue polarity and regulates mitotic spindle orientation in the breast epithelium.
    Bazzoun D, Adissu H, Wang L, Urazaev A, Tenvooren I, Fostok S, Chittiboyina S, Sturgis J, Hodges K, Chandramouly, G,     Vidi PA, Talhouk RS@, and Lelièvre SA@.
    Journal of Cell Science. 2019 132(10) pii jcs223313.
    These papers show that metabolic imbalance in obesity disrupts the normal organization of the breast epithelium, a critical step in cancer initiation.

  8. Silver nanoparticles selectively treat triple negative breast cancer cells without affecting non-malignant breast epithelial cells in vitro and in vivo.
    Swanner J, Fahrenholtz CD, Tenvooren I    , Bernish BW, Sears JJ, Hooker A, Furdui, CM, Alli E, Li W, Donati GL, Cook KL, Vidi PA, and Singh RN@.
    FASEB BioAdvances. 2019 1(10):639-660.

  9. Radial profile analysis of epithelial polarity in breast acini: a tool for primary (breast) cancer prevention.
    Manning L, Holmes J, Bonin K@, Vidi PA@.
    Frontiers in Medicine 2020 [link]

  10. Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis.
    Soto-Pantoja DR, Gaber M, Arnone AA, Bronson SM, Cruz-Diaz N, Wilson AS, Clear KYJ, Ramirez MU, Kucera GL, Levine EA, Lelièvre SA, Chaboub L, Chiba A, Yadav H,     Vidi PA, Cook KL@.
    Cancer Res. 2021 81(14):3890-3904 [link]
    This collaborative study provides a mechanistic link between (1) shifts in gut and mammary microbiomes caused by obesity and (2) breast cancer risk.


Theme 2 | Chromatin dynamics
  1. Nanoscale histone localization in live cells reveals reduced chromatin mobility in response to DNA damage. 
    Liu J*, Vidi PA*@, Lelievre SA, Irudayaraj JM@.  Journal of Cell Science. 2015 128(3):599-604. [link] 
    Description of transient changes in chromatin diffusion speed

  2. Structured illumination to spatially map intracellular molecular motions. 
    Bonin K@, Smelser A, Salvador-Moreno N, Holzwarth G, Wang K, Levi P, Vidi PA@.  Journal of  Biomedical Optics. 2018 23(5):1-8. [link]
    A novel optical system that we developed to track chromatin motions

  3. Special issue: Nuclear architecture and chromatin motions in the DNA damage response.
    Locatelli M, Vidi PA@. Mutat Res. 2020 821:111721.

  4. Performance of deep learning restoration method for the extraction of particle dynamics in noisy microscopy image sequences. Kefer P, Iqbal F, Locatelli M, Lawrimore J, Zhang M, Bloom K, Bonin K, @, Liu J@. Mol. Biol. Cell. 2021 32(9):903-914. [link]
    An objective approach to evaluate and 'sanity check' deep learning algorithms used for image analysis

  5. Characterization and implementation of a miniature X-ray system for live cell microscopy. 
    Prajapati S, Locatelli M, Sawyer C, Holmes J, Bonin K, Black P, Vidi PA@. Mutat Res. 2021 824:111772. [link]
    Methodology to irradiate cells on the microscope, to study early responses to DNA damage

  6. DNA damage reduces heterogeneity and coherence of chromatin motions.
    Locatelli M, Lawrimore J, Lin H, Sanaullah S, Seitz C, Segall D, Kefer P, Salvador Moreno N, Lietz B, Anderson R, Holmes J, Yuan C, Holzwarth G, Bloom KS, Liu J, Bonin K@, Vidi PA@. Proc Natl Acad Sci USA. 2022 119(29):e2205166119. [link]
    Spatial dependency of the chromatin response to DNA damage

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Theme 3 | Environmental exposures
  1. Personal samplers of bioavailable pesticides integrated with a hair follicle assay of DNA damage to assess environmental exposures and their associated risks in children. Vidi PA@, Anderson KA, Chen H, Anderson R, Salvador-Moreno N, Mora DC, Poutasse C, Laurienti PJ, Daniele SS, and Arcury  TA.  Mutation Research. 2017 822:27-33. [link]
    A novel noninvasive approach to relate environmental exposures and DNA damage in epithelial cells (of children)

FUNDING

CONTACT & LOCATION
​Pierre-Alexandre Vidi, PhD | e-mail
Group Leader, ICO
Adjunct Professor of Cancer Biology, Wake Forest School of Medicine​
Institut de Cancérologie de l’Ouest - Integrated Center for Oncology - ICO
Integrity of the Genome and Oncology (InGenO) Laboratory
15, rue André BOQUEL
49 055 Angers Cedex 02 – France
From the train station (Angers St Laud), take the tram (A line to CHU – Hôpital), or ride your bicycle along the west bank of the Maine river and take a left on the Rue de Monteclair.