Botnar Research Centre, Old Road, Headington, Oxford OX3 7LD
Srinivasa Rao Rao
Biography and research summary
I graduated with a degree in clinical medicine at the Jawaharlal Institute of Postgraduate Medical Education and Research, India. Following this, I obtained a Master of Science (by research) degree at the Indian Institute of Technology Madras; my research during this period focused on the role of microRNAs in the regulation of the Wnt signalling pathway. I studied for DPhil at the University of Oxford (2010-2014), in the Bone Oncology group headed by Dr. Claire Edwards. My DPhil project involved research into the process of epithelial-mesenchymal transition (EMT) in prostate cancer cells. We identified a novel regulator of EMT, demonstrating the functional importance of osteomimicry (prostate cancer cells exhibiting features of bone cells) in prostate cancer signalling pathways. This is particularly interesting in view of prostate cancer cells' predilection to metastasize to the skeletal system; bone metastasis in prostate cancer poses a significant problem in terms of patient morbidity and mortality.
I also developed novel high-throughput screening methods, in collaboration with the Daniel Ebner group at the Target Discovery Institute, University of Oxford, to quantify migration and cell morphology. Using these techniques I established a large dataset with thousands of data points describing how prostate cancer cell phenotype is altered by microRNAs. From this dataset, we identified several novel microRNA regulators of EMT and I am currently applying advanced computational methods to further interrogate this dataset.
My current research with Prof. Freddie Hamdy aims to apply DNA and RNA sequencing techniques to identify perturbations in gene expression that affect the progression of prostate cancer. To this end, I have established a custom prostate cancer-specific targeted sequencing gene panel, which can be used to interrogate difficult samples like formalin-fixed paraffin-embedded tissues for rare single nucleotide variants.
- Bioinformatics - DNA and RNA sequencing analysis (variant calling, differential expression) (Linux command-line, R, Python), mining (from cBioPortal, GEO, ArrayExpress) and analysis of large datasets using R/Bioconductor; image and video analysis using CellProfiler, Python/OpenCV
- Cell and molecular biology - Next-Generation Sequencing, high-throughput phenotypic screening and analysis, in vitro cell culture, fluorescence microscopy, qRT-PCR, western blot, ELISA, molecular cloning, flow cytometry
- In vivo - Intra-cardiac metastasis prostate cancer model, intra-tibial PCa model, in vivo tumour imaging
- Scientific writing and presentation - LaTex, Rmarkdown (knitr)
Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole genome sequencing with histopathological features
Rao SR. et al, (2023)
Evidence supporting safe diagnosis of coeliac disease in children with antitissue transglutaminase titre ≥5 times upper limit of normal.
Paul SP. et al, (2022), Arch dis child, 107, 747 - 751
Metabolic profiling of prostate cancer in skeletal microenvironments identifies G6PD as a key mediator of growth and survival.
Whitburn J. et al, (2022), Sci adv, 8
Loss of mutual protection between human osteoclasts and chondrocytes in damaged joints initiates osteoclast-mediated cartilage degradation by MMPs.
Larrouture QC. et al, (2021), Sci rep, 11
Diagnosis of celiac disease is being missed in over 80% of children particularly in those from socioeconomically deprived backgrounds.
Whitburn J. et al, (2021), Eur j pediatr, 180, 1941 - 1946