Molecular and Clinical Medicine, School of Medicine
Dr Naderi is a physician-scientist with expertise in medical oncology, cancer biology and genomics. Dr Naderi’s work experience includes associate professor and research group leader positions at the University of Iowa, University of Hawaii, and University of Queensland. Dr Naderi completed his medical oncology and cancer research fellowships at Mayo Clinic and University of Cambridge, respectively.
He holds MD and PhD degrees and has specialist qualifications as a medical oncologist in the UK (CCST) and USA (ABIM).
Molecular functions of SRARP and HSPB7 in malignancies
Chromosome 1p36 is frequently deleted in human cancers and 1p36.1 loss occurs in about 34% of tumours. However, despite extensive studies, there has been limited success for identifying candidate tumour suppressors on chromosome 1p36. Dr Naderi has recently identified and named a novel tumour suppressor gene, Steroid Receptor-Associated and Regulated Protein (SRARP) that is widely inactivated in malignancies and is located on chromosome 1p36.13.
His work initially identified SRARP (C1orf64) as a transcriptional corepressor of the androgen receptor (AR) that is co-expressed with AR in breast cancer cells. Dr Naderi’s subsequent studies have demonstrated that SRARP and HSPB7 are tumour suppressor gene pairs that are located 5.2 kb apart on chromosome 1p36.13. Furthermore, genome and epigenome-wide associations of SRARP with survival using the analysis of large genomic datasets also support its function as a tumour suppressor. Of note, DNA hypermethylation and lower expression of SRARP in primary tumours and normal adjacent tissues predict reduced survival. SRARP under-expression and copy-number loss are strong predictors of poor clinical and/or pathological features in malignancies of multiple tissue origins with highly significant odds ratios.
Dr Naderi is currently investigating the molecular functions and biomarker applications of SRARP and its gene pair HSPB7 in malignancies of multiple tissue origins.
Function of BEX2 in malignancies
Dr Naderi’s studies resulted in the discovery of BEX2 (Brain-Expressed-X-Linked 2) as a novel oncogene and revealed the significance of BEX2 in breast cancer carcinogenesis. His subsequent work showed that BEX2 promotes survival and growth of breast cancer cells. In this process, BEX2 regulates some of the critical steps involved in cancer cell survival and growth, including mitochondrial apoptosis cascade and G1 cell cycle. Of note, BEX2 expression is induced by ceramide and the overexpression of BEX2 protects cancer cells against mitochondrial apoptotic agents. Moreover, BEX2 regulates the activity of Protein Phosphatase 2A (PP2A) and the phosphorylation of key proteins involved in mitochondrial apoptosis such as Bcl-2 and BAD.
These findings have led to opening a new field of research in the last decade and currently the role of BEX2 is being studied in multiple malignancies with potential therapeutic applications. Dr Naderi is interested to delineate the molecular and biochemical mechanisms of BEX2 function and explore the translational implications of this protein in malignancies.