Line Manger: Professor Ian Mills 

LOCATION

Radiobiology Research Institute, Churchill Hospital, Headington, Oxford

Harri Itkonen, Principal Investigator, University of Helsinki

Biography

I qualified my Bachelors in Biotechnology from Vellore Institute of Technology, India (2002-2005) followed by Masters in Biotechnology (2005-2007) and Ph.D (2007-2011) from Amrita University, India with a prestigious fellowship from Council for Scientific and Industrial Research (CSIR) India. I also qualified the prestigious Department of Biotechnology (Ministry of Science & Technology, Govt of India) Junior Research Fellowship the same year. My Ph.D focused on finding and characterizing small molecule modulators of glucose transporter 4 (GLUT4), an insulin regulated GLUT isoform predominantly expressed in adipocytes and skeletal muscles. After my Ph.D, I moved to the University of Georgia, USA (2012-2013) for my postdoctoral research where I worked on an NIH funded project aimed at elucidating the roles of GLUTs and metabolic reprogramming in vascular smooth muscle cell phenotypic switching, a characteristic feature of intimal hyperplasia. My next postdoctoral appointment was in Augusta University, US (2014-2015) to study the role of sirtuin family of deacetylases in mediating cardiac protection by resveratrol and SRT1720 following haemorrhagic injury. In 2016, I moved to Queens University, Belfast to work briefly with Dr. Denise McDonald on NOTCH signalling dynamics in retinal micro-vascular endothelial cells and pericytes. I was then recruited by Prof. Ian G Mills in 2017 to the study the impact of glycosylation, primarily O-GlcNAcylation, on prostate cancer cells, the work which is continued in my current role in the Nuffield Department of Surgical Sciences.

My research focuses on genomic, transcriptomic and metabolic changes associated with androgen receptor (AR) signalling in prostate cancer. A comprehensive understanding of the molecular changes underpinning AR dependent PCa biology is instrumental in developing new therapies. In the last few years, O-GlcNAcylation, a post translational modification (PTM), has gained considerable interest as an important mediator of cellular reprogramming in PCa. Numerous studies indicate overexpression of OGT, the enzyme that catalyzes this PTM in cancers including PCa. Global changes in O-GlcNAcylome of PCa cells invariably lead to changes in transcriptomic and metabolic landscape of these cells. We hypothesize that there are a subset of AR and OGT co-regulated genes/proteins which can drive the progression of PCa and hence targeting this arm may be of clinical relevance. To identify AR and OGT co-regulated proteins, I have employed chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) in preclinical models of prostate cancer. The data generated from these studies are systematically analysed and compared to publically available data sets to identify interesting targets. In addition, I look at the metabolic signature of these cells under OGT knockdown conditions to understand metabolic dependencies of PCa cells on OGT and to identify combinatorial drug vulnerabilities. The overarching goal of these studies is to identify novel biomarkers and druggable targets which can eventually lead to developing new treatment strategies for PCa and also on repurposing existing drugs.