Upon successful fulfillment of my doctorate degree on the genetic engineering of Picornavirus, human Parechovirus 1, at the Essex Univ. 2001, I joined Cancer Research UK (CR-UK) London Research Institute (previously known as ICRF), where I carried out fundamental basic-research into the links between transcription, MAPKs signaling & diseases, including the cellular/molecular biology of cancer. My novel findings advanced knowledge in the pertinent field and also rewarded with publications in top research journals. In 2007, I joined the faculty of the UoN, where I started as a lecturer, and was promoted as an Associate Professor. At UoN, I have Research, Teaching and Administrative responsibilities, while established the Cancer Genetics & Stem Cell laboratory within the Division of Pre-clinical Oncology, currently with 2 post-docs, a technician and 5 PhD students.
My endless passion in cancer-biology and excellent achievements boasted publications in Nature, Science, etc and more recently J Exp Med & Stem Cells. As the lab name states, the group focused on exploring the mechanism for tumor initiation and maintenance of the stem cell, with combining a translational research in tissue-specific manner (physiology and related disease pathology), using a battery of state of the art approaches; including the generation, the analysis of tissues specific knockouts, genetic crossing onto tumor models, ex-vivo organoid culture, neoplastic stem cell models, ex-vivo lentiviral-based Cre/LoxP system, proteomic and the screening of protein-protein interactions, gene arrays, 3D/ co-culture and human tissue analysis, and mainly on formation of human colon/ intestinal and leukaemia cancers.
Gastrointestinal (GI) disorders (both neoplastic & non-neoplastic) are a big burden on the society & the health service. The intestine provides an attractive route to model biologically important intestinal processes and a unique opportunity for the direct identification and analysis of factors that contribute to development and maintenance of both normal as well as the development of neoplasia. However, little is known about intestinal stem cell components in crypt reproduction, the clonal architecture & the lineage relationships of normal and neoplastic intestinal crypts (in both benign & malignant disease).
My research team at Nottingham has demonstrated the robust research strength in bowel cancer (colon & small intestine) and has been dedicated in the tireless pursuit of a better understanding of intestinal homeostasis in the normal intestine, stem cell function & perturbation of these during tumor initiation. With a precisely dissected molecular basis using in vivo and ex vivo technologies, including tracing the cellular origin of cancer and organoid cultures for intestinal stem cell biology, in particular the links between transcription, signaling and disease(s), will allow us to negatively & positively instruct signaling pathways required for early neoplasia & GI repair. Furthermore, the extended contribution of research projects in my laboratory is anticipated to identify new "drug-gable" compound(s) that selectively target cancer stem cells from the bulk cells in the tumor.
Cancer genetics, Transgenic murine technology, Genome editing, Stem cells, Signalling, Transcription and Diseases
· Since the last decade, it is believed that specific signalling pathways; "WNT and MAPK" that control crucial steps during embryonic development are often inappropriately reactivated during tumorigenesis. Cancer cells seem to take advantage of cellular principles inherent to normal stem cells which are crucial for maintenance, repair and regenerative processes of most adult tissues such as the intestinal epithelium system. Intestinal Epithelial Stem (IES) cell self-renewal is a physiological mechanism that not only maintains a small pool of (stem) cells that are able to proliferate indefinitely but also at the same time produce a variety of differentiated cells that fulfil and maintain the function of the organ. Our research takes advantage of various mouse models in which the expression of a number of transcriptional modifiers (c-Jun, Fbw7 and TCF4/b-catenin) conditionally altered in the gut. We use those model systems to study the molecular and cellular basis of IES cell self-renewal, the interaction of stem cells with their specialized microenvironment (stem cell niche) and the relationship between stem cells and tumorigenesis.
· Epithelial stem cells assay (in vivo and in vitro), mouse genetics, gene targeting/transgenic, Cre/loxP system, transcriptome/ proteome analysis, ex vivo cell culture, FACS, histology, RNA and protein expression studies in vitro and in vivo.
· Our focus of studies will further extend the use of mouse models to study normal & malignant gastrointestinal tissues development as well as the intestinal epithelial stem cell biology. Our aim is to use these insights:
· to develop strategies that would allow expansion of adult stem cells in vitro and obtain insights into the development and the pathological events that lead to the cancer of the gut.
· to understand the molecular mechanism of the links between signalling, transcription and diseases that control the nature of stem cell and their progenitor lineage compartments and the nature of a "stem cell niche".
Medical Research Council (MRC), Cancer Research UK (CRUK), National Centre for the Replacement Refinement and Reduction of Animals in Research (NC3Rs)
IBRAHIM, E.E., BABAEI-JADIDI, R., SAADEDDIN, A., SPENCER-DENE, B., HOSSAINI, S., ABUZINADAH, M., LI, N., FADHIL, W., ILYAS, M., BONNET, D. and NATERI, A.S., 2012. Embryonic NANOG activity defines colorectal cancer stem cells and modulates through AP1- and TCF-dependent mechanisms Stem Cells. 30(10), 2076-2087
BABAEI-JADIDI, R., LI, N., SAADEDDIN, A., SPENCER-DENE, B., JANDKE, A., MUHAMMAD, B., IBRAHIM, E.E., MURALEEDHARAN, R., ABUZINADAH, M., DAVIS, H., LEWIS, A., WATSON, S., BEHRENS, A., TOMLINSON, I. and NATERI, A.S., 2011. FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation Journal of Experimental Medicine. 208(2), 295-312