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Dr Sebastian Oltean

Senior Lecturer in Disease Mechanisms and Novel Therapeutics

7417

Medical School Building F.08B

Sebastian studied clinical medicine at  “Iuliu Hatieganu” Medical School, Cluj-Napoca, Romania and trained as a junior doctor in Nephrology and Dialysis before moving to USA where he obtained a PhD from the University of Nebraska-Lincoln in 2004.This was followed by postdoctoral training at Duke University Medical Center (North Carolina, USA) where he became interested in studying the connections between alternative splicing and cancer. In 2008 he moved to the University of Bristol where he continued to study alternative splicing in vivo, with focus towards the importance of several genes splice isoforms (e.g VEGF, FGFR2) in cancer as well as kidney diseases and development of splice-based therapeutics. In 2012 he was appointed independent research fellow and principal investigator and developed his own research group in Bristol before moving to University of Exeter Medical School in 2017.

Qualifications

  • MBBS (1996) - “Iuliu Hatieganu” Medical School, Cluj, Romania
  • PhD (2004) – University of Nebraska-Lincoln, USA

Research

Research interests

The common denominator of my projects is the study of microcirculation in physiology and disease with a special emphasis on VEGF axis and other angiogenic molecules as well as links to trans-differentiation mechanisms such as endothelial- and epithelial-mesenchymal transitions. As disease models I focus on diabetes (emphasis on diabetic nephropathy and kidney fibrosis) and cancer (especially prostate cancer). At molecular level, I am interested how these processes are regulated by alternative splicing and how this may be manipulated for therapeutic advantage.

My research interests also include the study of alternative splicing in vivo, coordinated regulation of alternative splicing in physiology and disease as well as manipulation of splice isoforms choice for therapeutic goals. Alternative splicing is the main process that decides the diversity of proteins in our bodies. It is estimated that more than 90% of genes are alternatively spliced in humans and therefore this process affects all cellular properties. The function of the majority of splicing isoforms is not characterized yet. Numerous splicing isoforms have been associated with disease progression in recent years and there is much interest in understanding their contribution to pathogenesis and how this can be reversed.

Research projects

  • Modulation of alternative splicing as a novel therapeutic avenue in diabetic nephropathy
  • Alternative splicing control in epithelial-mesenchymal transitions / ESRP splice factors in prostate cancer
  • Detection of EGFR mutations in circulating tumour DNA in blood and urine form lung cancer patients

Research grants

  • 2019 Boehringer-Ingelheim
    Detection of genomic mutations in blood and urine free circulating tumour DNA (ctDNA) in inoperable and metastatic lung adenocarcinoma harboring an EGFR mutation on tissue.
  • 2019 Richard Bright VEGF Research Trust
    Diavit as a new treatment for diabetic nephropathy.
  • 2019 MRC Newton Fund UK-Thailand
    Evaluation of PRH/HHEX as a regulator of cholangiocarcinoma growth and metastasis.
  • 2018 British Heart Foundation
    mRNA splicing control in diabetes; a novel therapeutic strategy for treatment of diabetic nephropathy.
  • 2018 Prostate Cancer UK
    Targeting the ERG gene with splicing-switching oligonucleotides.

Invited lectures

  • 22nd World Congress on Advances in Oncology/ 20th International Symposium on Molecular Medicine  - Oct 2017, Athens, Greece – “Alternative splicing in epithelial-mesenchymal transitions”
  • BIT’s 5th World Congress of Diabetes – July 2017, Prague, Czech Republic – “Modulation of alternative splicing as a novel therapeutic avenue in diabetic nephropathy
  • ICGEB, Trieste, Italy – May 2017 – “Development of novel anti-angiogenic compounds based on modulation of alternative splicing”
  • Diabetic Nephropathy Research Symposium – May 2017, Cardiff – “Modulation of alternative splicing as a novel therapeutic avenue in diabetic nephropathy
  • 21st World Congress on Advances in Oncology/ 19th International Symposium on Molecular Medicine  - Oct 2016, Athens, Greece – “Modulators of alternative splicing as novel therapeutics in cancer”
  • University of Westminster – July 2016 – “Regulation of Alternative Splicing In Vivo and Drug-Discovery Screens using Splicing-Sensitive Fluorescent Reporters”
  • University of Newcastle / Institute of Genetic Medicine – May 2016 – “Modulation of alternative splicing a novel therapeutic avenue”
  • 1st International Conference in splicing - Sep 2016, Lisbon, Portugal – “Splicing-sensitive fluorescent reporters as tools for novel drug discovery”
  • Splicing and cancer workshop, Cancer Research Technology, May 2016, London – “Modulation of alternative splicing as a novel therapeutic avenue”
  • 8th Euro Global Diabetes Summit and Medicare Expo – Nov 2015, Valencia, Spain – “Therapeutic manipulation of alternative splicing in diabetic nephropathy”
  • BACR meeting “Advances in Cancer Drug Discovery”, 31Mar-01Apr 2014, Cambridge, UK – “Splicing-sensitive fluorescent reporters as tools for anti-cancer drug discovery”
  • 2nd Post-Eurasnet Meeting on Alternative Splicing, 18-20 Nov 2013, Trieste, Italy – “Hallmarks of alternative splicing in cancer
  • 4th World Congress on Diabetes and Metabolism, Aug 14-16, 2013, Chicago – “Alternative splicing in diabetic nephropathy”

Media Coverage

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