Interdisciplinary Life Science - PULSe Great research is a matter of choice

Sophie A. Lelièvre

Sophie A.  Lelièvre Profile Picture
Professor of Basic Medical Sciences and Cancer Pharmacology
D.V.M.-1990-Liege, Belgique M.S.- 1991 - Paris, France Ph.D - 1994 - Paris, France LL.M. (public health)- 2008- Rennes, France

Contact Info:

Training Group(s):
Chromatin and Regulation of Gene Expression
Molecular Signaling and Cancer Biology

Current Research Interests:

Research in the laboratory focuses on understanding the mechanisms by which the organization of components of the cell nucleus directs the expression and stability of the genome, and how tissue architecture influences nuclear organization. Our approach makes use of three-dimensional cultures of nonmalignant and malignant breast epithelial cells that recapitulate the formation of normal tissue structures (mammary acini) and tumor nodules, respectively. Using this system, nuclear structural proteins, including the nuclear mitotic apparatus protein NuMA, have been demonstrated to differentially relocate upon differentiation and tumorigenesis and their specific subcellular distribution has been shown to direct gene expression and cell behavior (e.g., invasive potential, proliferation, apoptosis). We have shown that NuMA participates in chromatin organization related to transcription control and DNA repair. Our current focus is to identify the binding partners of NuMA during differentiation and tumorigenesis and decipher the nuclear mechanisms by which NuMA controls higher order chromatin structures. We have unraveled sequences in NuMA that are potential regulators of its function and ligands involved in epigenetic mechanisms and response to environmental stress. This information will be used to further decipher the mechanisms by which nuclear structure controls cell phenotypes. A separate focus is to decipher the proteomic and genomic determinants of apical polarity, an important element of tissue architecture that is altered very early during breast cancer development. These determinants will be used as detection markers for the classification of breast cancers and as potential therapeutic targets. The effect of apical polarity on gene expression control is also being investigated. In addition, nanotechnology approaches, based on the use DNA tweezers, are being developed to control the expression of specific genes. These studies should yield strategies to fight against differentiation and proliferation disorders like cancers. Another area of research is the development of breast cancer prevention strategies by combining epigenomics research with the study of environmental risk and protective factors for breast tissue homeostasis. This aspect of the research is highly interdisciplinary and includes all aspects of public health necessary to develop prevention programs. Finally, collaborative endeavors with engineers are focused on the design of organ-on-a-chip models with readouts at the cell nucleus level for target discoveries and screening of drugs and materials for prevention and treatment of cancers.

Selected Publications:

selected list-past 5 years

Vidi P-A, Ling L, Lelièvre SA, Irudayaraj PJ. Nanoscale histone localization in live cells reveals reduced chromatin mobility in response to DNA damage. J Cell Sci. 128:599-604, 2015

Bazzoun D, Lelièvre SA, Talhouk R. “Beyond the channel: Role of connexins in regulating normal and cancerous processes in the mammary gland.” In Intercellular Communication in Cancer, Springer (In press)

Weaver C, Teegarden D, Hwalla N, Welch A, Lelièvre SA. International Breast Cancer and Nutrition: A model for research, training and policy in diet, epigenetics, and chronic disease prevention. Adv Nutr. 5:566-7, 2014.

Lelièvre SA. Taking a chance on epigenetics, (opinion article) Front. Genet. 2014

Vidi PA, Liu J, Jayaraman S, Dorfman G, Salles D, Gray M, Abad P, Moghe PV, Irudayaraj JMK, Wiesmüller L, and Lelièvre SA. The Nuclear Mitotic Apparatus Protein, NuMA, controls the presence of the ISWI ATPase SNF2h at DNA Breaks. Nucleic Acids Research, 42:6365-79, 2014.

Lelièvre SA, Hodges KB, Vidi PA. Application of theranostics to measure and treat cell heterogeneity in cancer. In Cancer Theranostics, Chapter 26, pp 494-516, 2014, Eds Shawn Chen and Stephen Wong., Elsevier.

Hodges KB, Bazzoun D, McDole K, Talhouk R and SA Lelièvre. TheRole of Epigenetics in Mammary Gland Development and Breast Cancer Risk, In Mammary Glands: Anatomy, Development and Diseases, Ed. E. Rucker, Series ‘Veterinary Sciences and Medicine’, Chapter IV, pp 63-112, 2014, Nova Science Publishers, Inc., New York

Vidi PA, Maleki T, Ochoa M, Wang L, Clark SM, Leary JF, Lelièvre SA. Disease-On-Chip: Mimicry of Tumor Growth in Mammary Ducts. Lab on chip, 14:172-7, 2014.

Lelièvre SA and CM. Weaver. Global Nutrition Research: Nutrition and Breast Cancer Prevention as a Model. Nutrition Rev, 71: 742–752, 2013

Vidi PA, Leary JF, Lelièvre SA. Building risk-on-a-chip models to improve breast cancer risk assessment and prevention, Frontier Review, Integr Biol (Camb). 5:1110-8, 2013.

Leary JF, Key J, Vidi P-A, Cooper CL, Kole A, Reece LM, Lelièvre SA. Human organ-on-a-chip BioMEMS devices for testing new diagnostic and therapeutic strategies. Microfuildics, BioMEMs, and Medical Microsystems XI, Proc. of SPIE, 8615:86150A, 2013

Bazzoun D, Lelièvre SA, Talhouk R. Polarity proteins as regulators of cell-cell junctional complexes: Implications for breast cancer. Pharmacol Ther. 138:418-27, 2013

Vidi P-A, MJ Bissell, and SA Lelièvre. “Three-dimensional culture of human breast epithelial cells: The how and the Why”. Epithelial Cell Culture, Methods in Mol Biol, 945:193-219, 2013

McDole K and Lelièvre SA. Comparative oncology to understand mammary cancer heterogeneity; Editorial, the Veterinary Journal 194:3-4, 2012

Yue S, J Cardenas-Morà, LS Chaboub, SA Lelièvre§ and J-X Cheng§. Label-free analysis of tissue polarity in live three-dimensional culture of breast epithelial cells using Raman spectroscopy. Biophys J 102:1215-23, 2012 §Senior coauthorship

Teegarden D, I Romieu, and SA Lelièvre. “Redefining the impact of nutrition on breast cancer incidence: Is epigenetics involved?” Nutrition Research Reviews 25:68-95, 2012

Vidi PA, G Chandramouly, M Gray, L Wang, E Liu, JJ. Kim, V Roukos, MJ Bissell, PV. Moghe, and SA Lelièvre. Interconnected Contribution of Tissue Morphogenesis and the Nuclear Protein NuMA to DNA Damage Response, J Cell Science 125(Pt 2):350-61, 2012

PC Abad, B Yagci, and SA Lelièvre. “Nanocellular processes.” Encyclopedia of Nanoscience and Nanotechnology, Vols 11-20, (Ed. H.S. Nalwa), 2011

Grafton§ MMG, L Wang§, P-A Vidi§, JF Leary, and SA. Lelièvre. “Breast on-a-chip: Mimicry of the channeling system of the breast for development of theranostics”. Integr Biol (Camb), 3: 451-9, 2011 (§ first coauthors).(selected as top story by Mammary Cell News)

SA Lelièvre. Tissue polarity-dependent control of mammary epithelial homeostasis and cancer development: An epigenomic perspective. Journal of Mammary Gland Biology and Neoplasia, 15:49-63, 2010

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