Wikipedia

Owen Sansom

Owen Sansom, FRSE.,[1] FMedSci[2] is the Director of the Cancer Research UK Beatson Institute (formerly known as the Beatson Institute for Cancer Research). He is known for his work determining the molecular hallmarks of colorectal cancer (CRC), including demonstrating the roles of the tumour suppressor protein APC and the WNT signalling pathway, as well as the involvement of intestinal stem cells in tumourigenesis[3][4]

Owen Sansom
Born
Owen James Sansom

(1975-04-21) 21 April 1975 (age 49)
Alma materUniversity of Nottingham
Known forWork on Wnt signalling in cancer
Awards
Scientific career
FieldsCancer
Institutions

Education

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After obtaining a BSc in genetics from the University of Nottingham and an MRes in Biology from the University of Manchester, Owen went on to obtain a PhD from the University of Edinburgh.[5][6]

Career

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Owen was a postdoctoral fellow at Cardiff University investigating the role of the APC gene in Wnt signalling and cancer.[3] In 2005, he became a Junior Group Leader at the Cancer Research UK Beatson Institute,[6] and in 2011 he was appointed the Institute's Deputy Director.[7][6] In 2016, the Institute's Director, Professor Karen Vousden moved to the Francis Crick Institute and became CRUK's chief scientist,[8] and Owen acted as interim Director of the Beatson Institute until being appointed as the next Director in 2017.[7][9] He also leads the CRUK Glasgow Centre,[10] which aims to bring together scientists and clinicians to work together on cancer research, drug discovery and patient care.

Research

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The Phenotype of APC loss in vivo and key effector pathways

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Owen was the first person to acutely delete the APC gene in the murine intestine, a model that he then used to elucidate the key pathways that APC controls in vivo.[3] Using this model system, Owen's group identified critical functional roles for genes such as MYC, RAC and MTOR.[11][12][13] Additionally, the use of this and other models has allowed Owen's group to identify potential chemoprevention strategies. For example, the group's work on aspirin showed that embryonic and perinatal exposure to aspirin suppresses neoplasia associated with the loss of Apc function.[14]

Neutrophils in colorectal and other cancers

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Owen's group showed that neutrophils are associated with the earliest stage of CRC, and using mouse models they showed that inhibition of the chemokine receptor CXCR2 could suppress both colitis and spontaneous cancer.[15] This was confirmed by the Dubois group in 2013.[16] Owen's group continued these studies into the pancreas to show that inhibition of CXCR2 suppresses metastasis in pancreatic cancer.[17]

The cell of origin of colorectal cancer

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In collaboration with Hans Clevers's laboratory, Owen's group showed that Lgr5-positive cells are an efficient cell of tumourigenesis.[4] Within the same study, they also showed that non-stem cells lacking APC could form lesions but would rarely progress. Following on from these studies, the group worked with Florian Greten's laboratory to show that additional mutations can cause an expansion in the cell of origin.[18] This work built upon work in Owen's laboratory on understanding the cooperation of APC with mutations in other genes such as KRAS and PTEN.[19][20]

Key regulators of metastasis

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Owen's group has developed models of metastatic disease and identified critical components of the metastatic pathway,[21] which has led to the design of trials specifically aimed at targeting metastatic disease in pancreatic cancer, e.g. Dasatanib in resectable pancreatic cancer patients. The group also provided definitive functional information on the role of mutant p53 in metastasis[21] and mechanisms behind the process: integrin recycling, LOX, RHO[22][23][24] The group also identified critical roles for RAC and its GEFs in melanoma migration and metastasis.[25][26]

Awards and honours

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In 2007, Owen won the Young Scientist Frank Rose Award in recognition of his contributions to translational cancer research[27] and in 2012 he was awarded the CRUK Future Leaders in Cancer Research Prize for his contributions to cancer research.[28] He was also elected a Fellow of the Royal Society of Edinburgh in 2012[1] and a Fellow of the Academy of Medical Sciences in 2017.[2]

References

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  1. ^ a b c "The Royal Society of Edinburgh: Professor Owen Sansom". Archived from the original on 2 October 2018. Retrieved 27 July 2018.
  2. ^ a b c "The Academy of Medical Sciences: Professor Owen Sansom". Archived from the original on 2 October 2018. Retrieved 27 July 2018.
  3. ^ a b c Sansom, OJ; Reed, KR; Hayes, AJ; Ireland, H; Brinkmann, H; Newton, IP; Batlle, E; Simon-Assmann, P; Clevers, H; Nathke, IS; Clarke, AR; Winton, DW (2004). "Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration". Genes & Development. 18 (12): 1385–1390. doi:10.1101/gad.287404. PMC 423189. PMID 15198980.
  4. ^ a b Barker, N; Ridgway, RA; van Es, JH; van de Wetering, M; Begthel, H; van den Born, M; Danenberg, E; Clarke, AR; Sansom, OJ; Clevers, H (2009). "Crypt stem cells as the cells-of-origin of intestinal cancer". Nature. 457 (7229): 608–11. Bibcode:2009Natur.457..608B. doi:10.1038/nature07602. PMID 19092804. S2CID 4422868.
  5. ^ PhD thesis: Genetic control of apoptosis and tumourigenesis in murine models of intestinal neoplasia
  6. ^ a b c "Beatson Institute: Owen Sansom". Archived from the original on 28 February 2018. Retrieved 31 July 2018.
  7. ^ a b "Q&A: Owen Sansom on stepping up as Director of our CRUK Beatson Institute". November 2017. Archived from the original on 1 September 2018. Retrieved 1 August 2018.
  8. ^ "Professor Karen Vousden appointed to chief scientist of Cancer Research UK". 8 July 2016. Archived from the original on 24 July 2018. Retrieved 31 July 2018.
  9. ^ "Beatson Institute: New Institute Director Appointed". Archived from the original on 24 October 2017. Retrieved 1 August 2018.
  10. ^ "Glasgow Cancer Centre: About Us". Archived from the original on 13 March 2017. Retrieved 1 August 2018.
  11. ^ Sansom, OJ; Meniel, VS; Muncan, V; Phesse, TJ; Wilkins, JA; Reed, KR; Vass, JK; Athineos, D; Clevers, H; Clarke, AR (2007). "Myc deletion rescues Apc deficiency in the small intestine". Nature. 446 (7136): 676–9. Bibcode:2007Natur.446..676S. doi:10.1038/nature05674. PMID 17377531.
  12. ^ Faller, WJ; Jackson, TJ; Knight, JR; Ridgway, RA; Jamieson, T; Karim, SA; Jones, C; Radulescu, S; Huels, DJ; Myant, KB; Dudek, KM; Casey, HA; Scopelliti, A; Cordero, JB; Vidal, M; Pende, M; Ryazanov, AG; Sonenberg, N; Meyuhas, O; Hall, MN; Bushell, M; Willis, AE; Sansom, OJ (2015). "mTORC1-mediated translational elongation limits intestinal tumour initiation and growth". Nature. 517 (7535): 497–500. Bibcode:2015Natur.517..497F. doi:10.1038/nature13896. PMC 4304784. PMID 25383520.
  13. ^ Myant, KB; Cammareri, P; McGhee, EJ; Ridgway, RA; Huels, DJ; Cordero, JB; Schwitalla, S; Kalna, G; Ogg, EL; Athineos, D; Timpson, P; Vidal, M; Murray, GI; Greten, FR; Anderson, KI; Sansom, OJ (2013). "ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation". Cell Stem Cell. 12 (6): 761–73. doi:10.1016/j.stem.2013.04.006. PMC 3690525. PMID 23665120.
  14. ^ Sansom, OJ; Stark, LA; Dunlop, MG; Clarke, AR (2001). "Suppression of intestinal and mammary neoplasia by lifetime administration of aspirin in Apc(Min/+) and Apc(Min/+), Msh2(-/-) mice". Cancer Research. 61 (19): 7060–4. PMID 11585736. Archived from the original on 28 August 2017. Retrieved 1 August 2018.
  15. ^ Jamieson, T; Clarke, M; Steele, CW; Samuel, MS; Neumann, J; Jung, A; Huels, D; Olson, MF; Das, S; Nibbs, RJ; Sansom, OJ (2012). "Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis". Journal of Clinical Investigation. 122 (9): 3127–44. doi:10.1172/JCI61067. PMC 3428079. PMID 22922255.
  16. ^ Katoh, H; Wang, D; Daikoku, T; Sun, H; Dey, SK; Dubois, RN (2013). "CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis". Cancer Cell. 24 (5): 631–44. doi:10.1016/j.ccr.2013.10.009. PMC 3928012. PMID 24229710.
  17. ^ Steele, CW; Karim, SA; Leach, JD; Bailey, P; Upstill-Goddard, R; Rishi, L; Foth, M; Bryson, S; McDaid, K; Wilson, Z; Eberlein, C; Candido, JB; Clarke, M; Nixon, C; Connelly, J; Jamieson, N; Carter, CR; Balkwill, F; Chang, DK; Evans, TR; Strathdee, D; Biankin, AV; Nibbs, RJ; Barry, ST; Sansom, OJ; Morton, JP (2016). "CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma". Cancer Cell. 29 (6): 832–45. doi:10.1016/j.ccell.2016.04.014. PMC 4912354. PMID 27265504.
  18. ^ Schwitalla, S; Fingerle, AA; Cammareri, P; Nebelsiek, T; Göktuna, SI; Ziegler, PK; Canli, O; Heijmans, J; Huels, DJ; Moreaux, G; Rupec, RA; Gerhard, M; Schmid, R; Barker, N; Clevers, H; Lang, R; Neumann, J; Kirchner, T; Taketo, MM; van den Brink, GR; Sansom, OJ; Arkan, MC; Greten, FR (2013). "Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties". Cell. 152 (1–2): 25–38. doi:10.1016/j.cell.2012.12.012. PMID 23273993.
  19. ^ Sansom, OJ; Meniel, V; Wilkins, JA; Cole, AM; Oien, KA; Marsh, V; Jamieson, TJ; Guerra, C; Ashton, GH; Barbacid, M; Clarke, AR (2006). "Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo". Proc Natl Acad Sci U S A. 103 (38): 14122–7. Bibcode:2006PNAS..10314122S. doi:10.1073/pnas.0604130103. PMC 1599922. PMID 16959882.
  20. ^ Marsh, V; Winton, DJ; Williams, GT; Dubois, N; Trumpp, A; Sansom, OJ; Clarke, AR (2008). "Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation". Nature Genetics. 40 (12): 1436–44. doi:10.1038/ng.256. PMID 19011632. S2CID 205346774.
  21. ^ a b Morton, JP; Timpson, P; Karim, SA; Ridgway, RA; Athineos, D; Doyle, B; Jamieson, NB; Oien, KA; Lowy, AM; Brunton, VG; Frame, MC; Evans, TROJ; Sansom (2010). "Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer". Proc Natl Acad Sci U S A. 107 (1): 246–51. Bibcode:2010PNAS..107..246M. doi:10.1073/pnas.0908428107. PMC 2806749. PMID 20018721.
  22. ^ Muller, PA; Caswell, PT; Doyle, B; Iwanicki, MP; Tan, EH; Karim, S; Lukashchuk, N; Gillespie, DA; Ludwig, RL; Gosselin, P; Cromer, A; Brugge, JS; Sansom, OJ; Norman, JC; Vousden, KH (2009). "Mutant p53 drives invasion by promoting integrin recycling". Cell. 139 (7): 1327–41. doi:10.1016/j.cell.2009.11.026. PMID 20064378.
  23. ^ Miller, BW; Morton, JP; Pinese, M; Saturno, G; Jamieson, NB; McGhee, E; Timpson, P; Leach, J; McGarry, L; Shanks, E; Bailey, P; Chang, D; Oien, K; Karim, S; Au, A; Steele, C; Carter, CR; McKay, C; Anderson, K; Evans, TR; Marais, R; Springer, C; Biankin, A; Erler, JT; Sansom, OJ (2015). "Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy". EMBO Molecular Medicine. 7 (8): 1063–7. doi:10.15252/emmm.201404827. PMC 4551344. PMID 26077591.
  24. ^ Timpson, P; McGhee, EJ; Morton, JP; von Kriegsheim, A; Schwarz, JP; Karim, SA; Doyle, B; Quinn, JA; Carragher, NO; Edward, M; Olson, MF; Frame, MC; Brunton, VG; Sansom, OJ; Anderson, KI (2011). "Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53". Cancer Research. 71 (3): 747–57. doi:10.1158/0008-5472.CAN-10-2267. PMC 3033324. PMID 21266354.
  25. ^ Lindsay, CR; Lawn, S; Campbell, AD; Faller, WJ; Rambow, F; Mort, RL; Timpson, P; Li, A; Cammareri, P; Ridgway, RA; Morton, JP; Doyle, B; Hegarty, S; Rafferty, M; Murphy, IG; McDermott, EW; Sheahan, K; Pedone, K; Finn, AJ; Groben, PA; et al. (2011). "P-Rex1 is required for efficient melanoblast migration and melanoma metastasis". Nature Communications. 2: 555. Bibcode:2011NatCo...2..555L. doi:10.1038/ncomms1560. PMC 3400057. PMID 22109529.
  26. ^ Li, A; Ma, Y; Jin, M; Mason, S; Mort, RL; Blyth, K; Larue, L; Sansom, OJ; Machesky, LM (2012). "Activated mutant NRas(Q61K) drives aberrant melanocyte signaling, survival, and invasiveness via a Rac1-dependent mechanism". Journal of Investigative Dermatology. 132 (11): 2610–21. doi:10.1038/jid.2012.186. PMC 3472562. PMID 22718121.
  27. ^ "BACR Awards". Archived from the original on 25 June 2017. Retrieved 1 August 2018.
  28. ^ "Future Leaders in Cancer Research Prize". 28 October 2015. Archived from the original on 10 August 2018. Retrieved 1 August 2018.
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