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Dr Sebastian Oltean

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.

Key publications | Publications by category | Publications by year

Key publications


Mavrou A, Brakspear K, Hamdollah-Zadeh M, Damodaran G, Babaei-Jadidi R, Oxley J, Gillatt DA, Ladomery MR, Harper SJ, Bates DO, et al (2015). Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer. Oncogene, 34(33), 4311-4319. Abstract.  Author URL.
Oltean S, Bates DO (2014). Hallmarks of alternative splicing in cancer. Oncogene, 33(46), 5311-5318. Abstract.  Author URL.
Amin EM, Oltean S, Hua J, Gammons MVR, Hamdollah-Zadeh M, Welsh GI, Cheung M-K, Ni L, Kase S, Rennel ES, et al (2011). WT1 mutants reveal SRPK1 to be a downstream angiogenesis target by altering VEGF splicing. Cancer Cell, 20(6), 768-780. Abstract.  Author URL.
Bonano VI, Oltean S, Garcia-Blanco MA (2007). A protocol for imaging alternative splicing regulation in vivo using fluorescence reporters in transgenic mice. Nat Protoc, 2(9), 2166-2181. Abstract.  Author URL.
Oltean S, Sorg BS, Albrecht T, Bonano VI, Brazas RM, Dewhirst MW, Garcia-Blanco MA (2006). Alternative inclusion of fibroblast growth factor receptor 2 exon IIIc in Dunning prostate tumors reveals unexpected epithelial mesenchymal plasticity. Proc Natl Acad Sci U S A, 103(38), 14116-14121. Abstract.  Author URL.

Publications by category


Journal articles

Bates DO, Morris JC, Oltean S, Donaldson LF (2017). Pharmacology of Modulators of Alternative Splicing. Pharmacol Rev, 69(1), 63-79. Abstract.  Author URL.
Bullock N, Oltean S (2017). The many faces of SRPK1. J Pathol, 241(4), 437-440. Abstract.  Author URL.
Stevens M, Oltean S (2016). Alternative Splicing in CKD. J Am Soc Nephrol, 27(6), 1596-1603. Abstract.  Author URL.
Mavrou A, Oltean S (2016). SRPK1 inhibition in prostate cancer: a novel anti-angiogenic treatment through modulation of VEGF alternative splicing. Pharmacol Res, 107, 276-281. Abstract.
Bullock N, Potts J, Simpkin AJ, Koupparis A, Harper SJ, Oxley J, Oltean S (2016). Serine-arginine protein kinase 1 (SRPK1), a determinant of angiogenesis, is upregulated in prostate cancer and correlates with disease stage and invasion. J Clin Pathol, 69(2), 171-175. Abstract.  Author URL.
Hamdollah Zadeh MA, Amin EM, Hoareau-Aveilla C, Domingo E, Symonds KE, Ye X, Heesom KJ, Salmon A, D'Silva O, Betteridge KB, et al (2015). Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance. Mol Oncol, 9(1), 167-178. Abstract.  Author URL.
Bunni J, Shelley-Fraser G, Stevenson K, Oltean S, Salmon A, Harper SJ, Carter JG, Bates DO (2015). Circulating levels of anti-angiogenic VEGF-A isoform (VEGF-Axxxb) in colorectal cancer patients predicts tumour VEGF-A ratios. Am J Cancer Res, 5(6), 2083-2089. Abstract.  Author URL.
Oltean S (2015). Modulators of alternative splicing as novel therapeutics in cancer. World J Clin Oncol, 6(5), 92-95. Abstract.  Author URL.
Mavrou A, Brakspear K, Hamdollah-Zadeh M, Damodaran G, Babaei-Jadidi R, Oxley J, Gillatt DA, Ladomery MR, Harper SJ, Bates DO, et al (2015). Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer. Oncogene, 34(33), 4311-4319. Abstract.  Author URL.
Munkley J, Oltean S, Vodák D, Wilson BT, Livermore KE, Zhou Y, Star E, Floros VI, Johannessen B, Knight B, et al (2015). The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer. Oncotarget, 6(33), 34358-34374. Abstract.  Author URL.  Full text.
Oltean S, Qiu Y, Ferguson JK, Stevens M, Neal C, Russell A, Kaura A, Arkill KP, Harris K, Symonds C, et al (2015). Vascular Endothelial Growth Factor-A165b is Protective and Restores Endothelial Glycocalyx in Diabetic Nephropathy. J Am Soc Nephrol, 26(8), 1889-1904. Abstract.  Author URL.
Oltean S, Bates DO (2014). Hallmarks of alternative splicing in cancer. Oncogene, 33(46), 5311-5318. Abstract.  Author URL.
Gammons MV, Lucas R, Dean R, Coupland SE, Oltean S, Bates DO (2014). Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma. Br J Cancer, 111(3), 477-485. Abstract.  Author URL.
Bates DO, Mavrou A, Qiu Y, Carter JG, Hamdollah-Zadeh M, Barratt S, Gammons MV, Millar AB, Salmon AHJ, Oltean S, et al (2013). Detection of VEGF-A(xxx)b isoforms in human tissues. PLoS One, 8(7). Abstract.  Author URL.
Oltean S, Gammons M, Hulse R, Hamdollah-Zadeh M, Mavrou A, Donaldson L, Salmon AH, Harper SJ, Ladomery MR, Bates DO, et al (2012). SRPK1 inhibition in vivo: modulation of VEGF splicing and potential treatment for multiple diseases. Biochem Soc Trans, 40(4), 831-835. Abstract.  Author URL.
Oltean S, Neal CR, Mavrou A, Patel P, Ahad T, Alsop C, Lee T, Sison K, Qiu Y, Harper SJ, et al (2012). VEGF165b overexpression restores normal glomerular water permeability in VEGF164-overexpressing adult mice. Am J Physiol Renal Physiol, 303(7), F1026-F1036. Abstract.  Author URL.
Armstrong AJ, Marengo MS, Oltean S, Kemeny G, Bitting RL, Turnbull JD, Herold CI, Marcom PK, George DJ, Garcia-Blanco MA, et al (2011). Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res, 9(8), 997-1007. Abstract.  Author URL.
Amin EM, Oltean S, Hua J, Gammons MVR, Hamdollah-Zadeh M, Welsh GI, Cheung M-K, Ni L, Kase S, Rennel ES, et al (2011). WT1 mutants reveal SRPK1 to be a downstream angiogenesis target by altering VEGF splicing. Cancer Cell, 20(6), 768-780. Abstract.  Author URL.
Hagau N, Slavcovici A, Gonganau DN, Oltean S, Dirzu DS, Brezoszki ES, Maxim M, Ciuce C, Mlesnite M, Gavrus RL, et al (2010). Clinical aspects and cytokine response in severe H1N1 influenza a virus infection. Crit Care, 14(6). Abstract.  Author URL.
Qiu Y, Ferguson J, Oltean S, Neal CR, Kaura A, Bevan H, Wood E, Sage LM, Lanati S, Nowak DG, et al (2010). Overexpression of VEGF165b in podocytes reduces glomerular permeability. J Am Soc Nephrol, 21(9), 1498-1509. Abstract.  Author URL.
Qiu Y, Hoareau-Aveilla C, Oltean S, Harper SJ, Bates DO (2009). The anti-angiogenic isoforms of VEGF in health and disease. Biochem Soc Trans, 37(Pt 6), 1207-1213. Abstract.  Author URL.
Oltean S, Febbo PG, Garcia-Blanco MA (2008). Dunning rat prostate adenocarcinomas and alternative splicing reporters: powerful tools to study epithelial plasticity in prostate tumors in vivo. Clin Exp Metastasis, 25(6), 611-619. Abstract.  Author URL.
Bonano VI, Oltean S, Garcia-Blanco MA (2007). A protocol for imaging alternative splicing regulation in vivo using fluorescence reporters in transgenic mice. Nat Protoc, 2(9), 2166-2181. Abstract.  Author URL.
Col B, Oltean S, Banerjee R (2007). Translational regulation of human methionine synthase by upstream open reading frames. Biochim Biophys Acta, 1769(9-10), 532-540. Abstract.  Author URL.
Oltean S, Sorg BS, Albrecht T, Bonano VI, Brazas RM, Dewhirst MW, Garcia-Blanco MA (2006). Alternative inclusion of fibroblast growth factor receptor 2 exon IIIc in Dunning prostate tumors reveals unexpected epithelial mesenchymal plasticity. Proc Natl Acad Sci U S A, 103(38), 14116-14121. Abstract.  Author URL.
Bonano VI, Oltean S, Brazas RM, Garcia-Blanco MA (2006). Imaging the alternative silencing of FGFR2 exon IIIb in vivo. RNA, 12(12), 2073-2079. Abstract.  Author URL.
Oltean S, Banerjee R (2005). A B12-responsive internal ribosome entry site (IRES) element in human methionine synthase. J Biol Chem, 280(38), 32662-32668. Abstract.  Author URL.
Spanu C, Oltean S (2003). Familial phosphoglycerate kinase deficiency associated with rhabdomyolysis and acute renal failure: abnormality in mRNA splicing?. Nephrol Dial Transplant, 18(2), 445-446. Author URL.
Oltean S, Banerjee R (2003). Nutritional modulation of gene expression and homocysteine utilization by vitamin B12. J Biol Chem, 278(23), 20778-20784. Abstract.  Author URL.

Publications by year


2017

Bates DO, Morris JC, Oltean S, Donaldson LF (2017). Pharmacology of Modulators of Alternative Splicing. Pharmacol Rev, 69(1), 63-79. Abstract.  Author URL.
Bullock N, Oltean S (2017). The many faces of SRPK1. J Pathol, 241(4), 437-440. Abstract.  Author URL.

2016

Stevens M, Oltean S (2016). Alternative Splicing in CKD. J Am Soc Nephrol, 27(6), 1596-1603. Abstract.  Author URL.
Mavrou A, Oltean S (2016). SRPK1 inhibition in prostate cancer: a novel anti-angiogenic treatment through modulation of VEGF alternative splicing. Pharmacol Res, 107, 276-281. Abstract.
Bullock N, Potts J, Simpkin AJ, Koupparis A, Harper SJ, Oxley J, Oltean S (2016). Serine-arginine protein kinase 1 (SRPK1), a determinant of angiogenesis, is upregulated in prostate cancer and correlates with disease stage and invasion. J Clin Pathol, 69(2), 171-175. Abstract.  Author URL.

2015

Hamdollah Zadeh MA, Amin EM, Hoareau-Aveilla C, Domingo E, Symonds KE, Ye X, Heesom KJ, Salmon A, D'Silva O, Betteridge KB, et al (2015). Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance. Mol Oncol, 9(1), 167-178. Abstract.  Author URL.
Bunni J, Shelley-Fraser G, Stevenson K, Oltean S, Salmon A, Harper SJ, Carter JG, Bates DO (2015). Circulating levels of anti-angiogenic VEGF-A isoform (VEGF-Axxxb) in colorectal cancer patients predicts tumour VEGF-A ratios. Am J Cancer Res, 5(6), 2083-2089. Abstract.  Author URL.
Oltean S (2015). Modulators of alternative splicing as novel therapeutics in cancer. World J Clin Oncol, 6(5), 92-95. Abstract.  Author URL.
Mavrou A, Brakspear K, Hamdollah-Zadeh M, Damodaran G, Babaei-Jadidi R, Oxley J, Gillatt DA, Ladomery MR, Harper SJ, Bates DO, et al (2015). Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer. Oncogene, 34(33), 4311-4319. Abstract.  Author URL.
Munkley J, Oltean S, Vodák D, Wilson BT, Livermore KE, Zhou Y, Star E, Floros VI, Johannessen B, Knight B, et al (2015). The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer. Oncotarget, 6(33), 34358-34374. Abstract.  Author URL.  Full text.
Oltean S, Qiu Y, Ferguson JK, Stevens M, Neal C, Russell A, Kaura A, Arkill KP, Harris K, Symonds C, et al (2015). Vascular Endothelial Growth Factor-A165b is Protective and Restores Endothelial Glycocalyx in Diabetic Nephropathy. J Am Soc Nephrol, 26(8), 1889-1904. Abstract.  Author URL.

2014

Oltean S, Bates DO (2014). Hallmarks of alternative splicing in cancer. Oncogene, 33(46), 5311-5318. Abstract.  Author URL.
Gammons MV, Lucas R, Dean R, Coupland SE, Oltean S, Bates DO (2014). Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma. Br J Cancer, 111(3), 477-485. Abstract.  Author URL.

2013

Bates DO, Mavrou A, Qiu Y, Carter JG, Hamdollah-Zadeh M, Barratt S, Gammons MV, Millar AB, Salmon AHJ, Oltean S, et al (2013). Detection of VEGF-A(xxx)b isoforms in human tissues. PLoS One, 8(7). Abstract.  Author URL.

2012

Oltean S, Gammons M, Hulse R, Hamdollah-Zadeh M, Mavrou A, Donaldson L, Salmon AH, Harper SJ, Ladomery MR, Bates DO, et al (2012). SRPK1 inhibition in vivo: modulation of VEGF splicing and potential treatment for multiple diseases. Biochem Soc Trans, 40(4), 831-835. Abstract.  Author URL.
Oltean S, Neal CR, Mavrou A, Patel P, Ahad T, Alsop C, Lee T, Sison K, Qiu Y, Harper SJ, et al (2012). VEGF165b overexpression restores normal glomerular water permeability in VEGF164-overexpressing adult mice. Am J Physiol Renal Physiol, 303(7), F1026-F1036. Abstract.  Author URL.

2011

Armstrong AJ, Marengo MS, Oltean S, Kemeny G, Bitting RL, Turnbull JD, Herold CI, Marcom PK, George DJ, Garcia-Blanco MA, et al (2011). Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res, 9(8), 997-1007. Abstract.  Author URL.
Amin EM, Oltean S, Hua J, Gammons MVR, Hamdollah-Zadeh M, Welsh GI, Cheung M-K, Ni L, Kase S, Rennel ES, et al (2011). WT1 mutants reveal SRPK1 to be a downstream angiogenesis target by altering VEGF splicing. Cancer Cell, 20(6), 768-780. Abstract.  Author URL.

2010

Hagau N, Slavcovici A, Gonganau DN, Oltean S, Dirzu DS, Brezoszki ES, Maxim M, Ciuce C, Mlesnite M, Gavrus RL, et al (2010). Clinical aspects and cytokine response in severe H1N1 influenza a virus infection. Crit Care, 14(6). Abstract.  Author URL.
Qiu Y, Ferguson J, Oltean S, Neal CR, Kaura A, Bevan H, Wood E, Sage LM, Lanati S, Nowak DG, et al (2010). Overexpression of VEGF165b in podocytes reduces glomerular permeability. J Am Soc Nephrol, 21(9), 1498-1509. Abstract.  Author URL.

2009

Qiu Y, Hoareau-Aveilla C, Oltean S, Harper SJ, Bates DO (2009). The anti-angiogenic isoforms of VEGF in health and disease. Biochem Soc Trans, 37(Pt 6), 1207-1213. Abstract.  Author URL.

2008

Oltean S, Febbo PG, Garcia-Blanco MA (2008). Dunning rat prostate adenocarcinomas and alternative splicing reporters: powerful tools to study epithelial plasticity in prostate tumors in vivo. Clin Exp Metastasis, 25(6), 611-619. Abstract.  Author URL.

2007

Bonano VI, Oltean S, Garcia-Blanco MA (2007). A protocol for imaging alternative splicing regulation in vivo using fluorescence reporters in transgenic mice. Nat Protoc, 2(9), 2166-2181. Abstract.  Author URL.
Col B, Oltean S, Banerjee R (2007). Translational regulation of human methionine synthase by upstream open reading frames. Biochim Biophys Acta, 1769(9-10), 532-540. Abstract.  Author URL.

2006

Oltean S, Sorg BS, Albrecht T, Bonano VI, Brazas RM, Dewhirst MW, Garcia-Blanco MA (2006). Alternative inclusion of fibroblast growth factor receptor 2 exon IIIc in Dunning prostate tumors reveals unexpected epithelial mesenchymal plasticity. Proc Natl Acad Sci U S A, 103(38), 14116-14121. Abstract.  Author URL.
Bonano VI, Oltean S, Brazas RM, Garcia-Blanco MA (2006). Imaging the alternative silencing of FGFR2 exon IIIb in vivo. RNA, 12(12), 2073-2079. Abstract.  Author URL.

2005

Oltean S, Banerjee R (2005). A B12-responsive internal ribosome entry site (IRES) element in human methionine synthase. J Biol Chem, 280(38), 32662-32668. Abstract.  Author URL.

2003

Spanu C, Oltean S (2003). Familial phosphoglycerate kinase deficiency associated with rhabdomyolysis and acute renal failure: abnormality in mRNA splicing?. Nephrol Dial Transplant, 18(2), 445-446. Author URL.
Oltean S, Banerjee R (2003). Nutritional modulation of gene expression and homocysteine utilization by vitamin B12. J Biol Chem, 278(23), 20778-20784. Abstract.  Author URL.

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”

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