Upon successful fulfilment of my doctorate 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 first basic-research into the links between transcription, MAPKs signalling & diseases, including the cellular/molecular biology of cancer. My novel findings advanced knowledge in the relevant 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 established the Cancer Genetics & Stem Cell laboratory within the Cancer Biology Unit at the Division of Cancer & Stem Cells, while having Teaching and administrative responsibilities.
As the lab name states, the group focused on exploring the mechanism for tumour initiation and maintenance of the stem cell. We combine the basic and translational research in a cell and tissue-specific manner (physiology and related disease pathology). We study tissues specific knockouts and tumour models, 3D 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 the formation of human GI and blood 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 tumour 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 signalling 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 tumour.
I'm teaching the postgraduate MSc, undergraduates and medics students for:
Oncogenes & Tumour Suppressor Genes
Transgenic Murine Technology
The ubiquitin-proteasome system
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, Fbxw7 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 hematopoietic stem cells assays (in vivo and in vitro), gene targeting/transgenic, Cre/LoxP and CRISPR-Cas systems, transcriptome/ proteome analysis, 3D Organoid and Spheroid culture, FACS, histology, RNA and protein expression studies in vitro and in vivo.
We aim; 1) 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 cancer. 2) to understand the molecular mechanism of the links between signalling, and cancer-associated gene expression regulation via transcription, post-translation modifications that control the heterogeneity of normal and cancer stem-like cell /progenitor cells. 3) to develop transplantable models for tumour growth and metastasis formation. 4) to define compounds and drugs targeting cancer Stem-like cells.
Medical Research Council (MRC), Cancer Research UK (CRUK), National Centre for the Replacement Refinement and Reduction of Animals in Research (NC3Rs)
NINGNING LI, ROYA BABAEI-JADIDI, FEDERICA LORENZI, BRADLEY SPENCER-DENE, PHILIP CLARKE, ENRIC DOMINGO, EUGENE TULCHINSKY, ROBERT G. J. VRIES, DAVID KERR, YIHANG PAN, YULONG HE, DAVID O. BATES, IAN TOMLINSON, HANS CLEVERS and ABDOLRAHMAN S. NATERI, 2019. An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance: FBXW7/ZEB2 links EMT to CRC-SCs Oncogenesis. 8(3), BELAL A. MUHAMMAD, SHEEMA ALMOZYAN, ROYA BABAEI-JADIDI, EMENIKE K. ONYIDO, ANAS SAADEDDIN, SEYED HOSSEIN KASHFI, BRADLEY SPENCER-DENE, MOHAMMAD ILYAS, ANBARASU LOURDUSAMY, AXEL BEHRENS and ABDOLRAHMAN S. NATERI, 2018. FLYWCH1, a Novel Suppressor of Nuclear
b-Catenin, Regulates Migration and Morphology
in Colorectal Cancer: FLYWCH1 antagonizes b-catenin/TCF4 signaling Molecular Cancer Research: Mol Cancer Res.. 12, 1977-1990
AHMED M, CHAUDHARI K, BABAEI-JADIDI R, DEKKER LV and NATERI AS, 2017. Emerging Drugs Targeting Epithelial Cancer Stem-like Cells: A Concise Review. Stem cells (Dayton, Ohio). 35(4), 839-850