Dr Nicole Clarke
Lecturer in Gene Regulation
Tel: +44-(0)115-95-15058
Fax: +44-(0)115-84-68877
Email: nicole.clarke@nottingham.ac.uk
Academic career
BSc, University of Toronto, Toronto, Ontario, Canada
MPhil, PhD, Department of Biological Sciences, Columbia University, New York, NY, USA
Postdoctoral work at Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Strasbourg, France
Joined the School of Pharmacy in 2006
Research
Research interests of the laboratory include understanding mechanisms underlying the tumour suppressor activity of interferon Regulatory factors (IRFs). Tumour suppressors and other proteins involved in anti-proliferative signals in the cell are crucial for preventing neoplastic conversion of cells. We have previously shown that the tumour susceptibility gene, IRF-1 is an important mediator of TRAIL-induced cell death of cancer cells after retinoid/interferon treatment. Currently, we are interested in defining the transcriptional and cellular networks controlling the expression/function of IRF-1 and identifying the transcriptional targets of the IRF family using genome wide Chip-on-chip technology.
Present topics under investigation include:
- Studying the role of post-transcriptional modifications such as phosphorylation, in regulating the activity and function of IRF1.
- Identifying the transcriptional networks controlled by IRF-1 and IRF-8
- Identifying proteins which interact with IRF-1
- Identifying key mediators controlling IRF-1 expression
Ultimately we wish to relate the information gained from our studies to cancer biology and therapy. By understanding the basic mechanisms involved in IRF tumour suppressor activity, we hope to identify new ways to therapeutically target IRFs for cancer therapy.
Selected publications
Frontini, M., Vijayakumar, M., Garvin, A., and Clarke N. (2009) A ChIP-chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response. Nucleic Acids Res. 37: 1073-1085. [Pubmed]
Clarke N, Jimenez-Lara AM, Voltz E, Gronemeyer H. (2004) Tumor suppressor IRF-1 mediates retinoid and interferon anticancer signaling to death ligand TRAIL. EMBO J. 23: 3051-3060. [Pubmed]
Clarke N, Nebbioso A, Altucci L, Gronemeyer H. (2005) TRAIL: at the center of drugable anti-tumor pathways. Cell Cycle. 4: 914-918. [Pubmed]
Nebbioso A, Clarke N, Voltz E, Germain E, Ambrosino C, Bontempo P, Alvarez R, Schiavone EM, Ferrara F, Bresciani F, Weisz A, de Lera AR, Gronemeyer H, Altucci L. (2005) Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nat Med. 11: 77-84. [Pubmed]
