Owen Sansom Explained

Owen Sansom
Birth Name:Owen James Sansom
Birth Date:1975 4, df=yes
Fields:Cancer
Alma Mater:University of Nottingham
Known For:Work on Wnt signalling in cancer

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]

Education

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.[4]

Career

Owen was a postdoctoral fellow at Cardiff University investigating the role of the APC gene in Wnt signalling and cancer.[5] 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. In 2016, the Institute's Director, Professor Karen Vousden moved to the Francis Crick Institute and became CRUK's chief scientist,[7] and Owen acted as interim Director of the Beatson Institute until being appointed as the next Director in 2017.[8] [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

The Phenotype of APC loss in vivo and key effector pathways

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. 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

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

In collaboration with Hans Clevers's laboratory, Owen's group showed that Lgr5-positive cells are an efficient cell of tumourigenesis. 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

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 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

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 and a Fellow of the Academy of Medical Sciences in 2017.

Notes and References

  1. Web site: The Royal Society of Edinburgh: Professor Owen Sansom . 27 July 2018 . https://web.archive.org/web/20181002182105/https://www.rse.org.uk/fellow/owen-sansom/ . 2 October 2018 . live . dmy-all .
  2. Web site: The Academy of Medical Sciences: Professor Owen Sansom . 27 July 2018 . https://web.archive.org/web/20181002141802/https://acmedsci.ac.uk/fellows/fellows-directory/ordinary-fellows/fellow/Professor-Owen-Sansom-0019237 . 2 October 2018 . live . dmy-all .
  3. 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. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 457. 7229. 608–11. 2009. 19092804. 10.1038/nature07602. 2009Natur.457..608B. 4422868.
  4. http://ethos.bl.uk/OrderDetails.do?did=3&uin=uk.bl.ethos.661579 PhD thesis: Genetic control of apoptosis and tumourigenesis in murine models of intestinal neoplasia
  5. 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 . Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration . Genes & Development . 18 . 12 . 1385–1390 . 2004 . 15198980 . 423189 . 10.1101/gad.287404 . dmy-all.
  6. Web site: Beatson Institute: Owen Sansom . 31 July 2018 . https://web.archive.org/web/20180228091022/http://www.beatson.gla.ac.uk/Invasion-and-Metastasis/owen-sansom-colorectal-cancer-and-wnt-signalling.html . 28 February 2018 . live . dmy-all .
  7. Web site: Professor Karen Vousden appointed to chief scientist of Cancer Research UK . 31 July 2018 . https://web.archive.org/web/20180724154207/https://www.cancerresearchuk.org/about-us/cancer-news/press-release/2016-07-10-professor-karen-vousden-appointed-to-chief-scientist-of-cancer-research-uk . 24 July 2018 . live . dmy-all . 8 July 2016 .
  8. Web site: Q&A: Owen Sansom on stepping up as Director of our CRUK Beatson Institute . 1 August 2018 . https://web.archive.org/web/20180901044556/https://www.cancerresearchuk.org/funding-for-researchers/research-features/2017-11-01-qa-owen-sansom-steps-up-as-director-of-our-cruk-beatson-institute . 1 September 2018 . live . dmy-all . November 2017 .
  9. Web site: Beatson Institute: New Institute Director Appointed . 1 August 2018 . https://web.archive.org/web/20171024190041/http://www.beatson.gla.ac.uk/Current-News/new-director-appointed.html . 24 October 2017 . live . dmy-all .
  10. Web site: Glasgow Cancer Centre: About Us . 1 August 2018 . https://web.archive.org/web/20170313024153/http://www.glasgowcancer.org/about-us/ . 13 March 2017 . live . dmy-all .
  11. Sansom . OJ. Meniel . VS. Muncan . V. Phesse . TJ. Wilkins . JA. Reed . KR. Vass . JK. Athineos . D. Clevers . H. Clarke . AR. Myc deletion rescues Apc deficiency in the small intestine. Nature. 446. 7136. 676–9. 2007. 17377531. 10.1038/nature05674. 2007Natur.446..676S. free.
  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. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature. 517. 7535. 497–500. 2015. 25383520. 4304784 . 10.1038/nature13896. 2015Natur.517..497F.
  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. 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. 2013. 23665120. 3690525 . 10.1016/j.stem.2013.04.006.
  14. Sansom . OJ . Stark . LA . Dunlop . MG . Clarke . AR . 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 . 2001 . 11585736 . 1 August 2018 . https://web.archive.org/web/20170828023529/http://cancerres.aacrjournals.org/content/61/19/7060 . 28 August 2017 . live . dmy-all.
  15. Jamieson . T . Clarke . M . Steele . CW . Samuel . MS . Neumann . J . Jung . A . Huels . D . Olson . MF . Das . S . Nibbs . RJ . Sansom . OJ . Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis . Journal of Clinical Investigation . 122 . 9 . 3127–44 . 2012 . 22922255 . 3428079 . 10.1172/JCI61067 . dmy-all.
  16. Katoh . H. Wang . D. Daikoku . T. Sun . H. Dey . SK. Dubois . RN. CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis. Cancer Cell. 24. 5. 631–44. 2013. 24229710. 3928012. 10.1016/j.ccr.2013.10.009.
  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. CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell. 29. 6. 832–45. 2016. 27265504. 4912354. 10.1016/j.ccell.2016.04.014.
  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. Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell. 152. 1–2. 25–38. 2013. 23273993. 10.1016/j.cell.2012.12.012. free.
  19. Sansom . OJ. Meniel . V. Wilkins . JA. Cole . AM. Oien . KA. Marsh . V. Jamieson . TJ. Guerra . C. Ashton . GH. Barbacid . M. Clarke . AR. 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. 2006. 16959882. 1599922 . 10.1073/pnas.0604130103. 2006PNAS..10314122S. free.
  20. Marsh . V. Winton . DJ. Williams . GT. Dubois . N. Trumpp . A. Sansom . OJ. Clarke . AR. Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation. Nature Genetics. 40. 12. 1436–44. 2008. 19011632. 10.1038/ng.256. 205346774.
  21. 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 . Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer . Proc Natl Acad Sci U S A . 107 . 1 . 246–51 . 2010 . 20018721 . 2806749 . 10.1073/pnas.0908428107 . dmy-all. 2010PNAS..107..246M . free .
  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. Mutant p53 drives invasion by promoting integrin recycling. Cell. 139. 7. 1327–41. 2009. 20064378. 10.1016/j.cell.2009.11.026. free.
  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 . 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 . 2015 . 26077591 . 4551344 . 10.15252/emmm.201404827 . dmy-all.
  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 . Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53 . Cancer Research . 71 . 3 . 747–57 . 2011 . 21266354 . 3033324 . 10.1158/0008-5472.CAN-10-2267 . dmy-all.
  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. etal. P-Rex1 is required for efficient melanoblast migration and melanoma metastasis. Nature Communications. 2. 555. 2011. 22109529. 3400057 . 10.1038/ncomms1560. 2011NatCo...2..555L.
  26. Li . A. Ma . Y. Jin . M. Mason . S. Mort . RL. Blyth . K. Larue . L. Sansom . OJ. Machesky . LM. Activated mutant NRas(Q61K) drives aberrant melanocyte signaling, survival, and invasiveness via a Rac1-dependent mechanism. Journal of Investigative Dermatology. 132. 11. 2610–21. 2012. 22718121. 3472562. 10.1038/jid.2012.186.
  27. Web site: BACR Awards . 1 August 2018 . https://web.archive.org/web/20170625134540/http://bacr.org.uk/awards/10 . 25 June 2017 . live . dmy-all .
  28. Web site: Future Leaders in Cancer Research Prize . 1 August 2018 . https://web.archive.org/web/20180810090558/https://www.cancerresearchuk.org/funding-for-researchers/how-we-deliver-research/our-research-prizes/future-leaders-in-cancer-research-prize#members_gallery_14 . 10 August 2018 . live . dmy-all . 28 October 2015 .

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