Owen Sansom

Last updated

Owen Sansom
Born
Owen James Sansom

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

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]

Contents

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. [5] [6]

Career

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

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. [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

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. [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

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

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]

Related Research Articles

<span class="mw-page-title-main">Pancreatic cancer</span> Type of endocrine gland cancer

Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass. These cancerous cells have the ability to invade other parts of the body. A number of types of pancreatic cancer are known.

<span class="mw-page-title-main">Lamina propria</span> Thin connective layer forming part of the mucous membranes

The lamina propria is a thin layer of connective tissue that forms part of the moist linings known as mucous membranes or mucosae, which line various tubes in the body, such as the respiratory tract, the gastrointestinal tract, and the urogenital tract.

<span class="mw-page-title-main">Familial adenomatous polyposis</span> Pre-cancerous intestinal polyps

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition in which numerous adenomatous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs when they are left untreated. Three variants are known to exist, FAP and attenuated FAP are caused by APC gene defects on chromosome 5 while autosomal recessive FAP is caused by defects in the MUTYH gene on chromosome 1. Of the three, FAP itself is the most severe and most common; although for all three, the resulting colonic polyps and cancers are initially confined to the colon wall. Detection and removal before metastasis outside the colon can greatly reduce and in many cases eliminate the spread of cancer.

The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis and in the initiation of metastasis in cancer progression.

<span class="mw-page-title-main">CXCL1</span> Mammalian protein found in Homo sapiens

The chemokine ligand 1 (CXCL1) is a small peptide belonging to the CXC chemokine family that acts as a chemoattractant for several immune cells, especially neutrophils or other non-hematopoietic cells to the site of injury or infection and plays an important role in regulation of immune and inflammatory responses. It was previously called GRO1 oncogene, GROα, neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MGSA-α). CXCL1 was first cloned from a cDNA library of genes induced by platelet-derived growth factor (PDGF) stimulation of BALB/c-3T3 murine embryonic fibroblasts and named "KC" for its location in the nitrocellulose colony hybridization assay. This designation is sometimes erroneously believed to be an acronym and defined as "keratinocytes-derived chemokine". Rat CXCL1 was first reported when NRK-52E cells were stimulated with interleukin-1β (IL-1β) and lipopolysaccharide (LPS) to generate a cytokine that was chemotactic for rat neutrophils, cytokine-induced neutrophil chemoattractant (CINC). In humans, this protein is encoded by the gene CXCL1 and is located on human chromosome 4 among genes for other CXC chemokines.

<span class="mw-page-title-main">CXCL2</span> Mammalian protein found in Homo sapiens

Chemokine ligand 2 (CXCL2) is a small cytokine belonging to the CXC chemokine family that is also called macrophage inflammatory protein 2-alpha (MIP2-alpha), Growth-regulated protein beta (Gro-beta) and Gro oncogene-2 (Gro-2). CXCL2 is 90% identical in amino acid sequence as a related chemokine, CXCL1. This chemokine is secreted by monocytes and macrophages and is chemotactic for polymorphonuclear leukocytes and hematopoietic stem cells. The gene for CXCL2 is located on human chromosome 4 in a cluster of other CXC chemokines. CXCL2 mobilizes cells by interacting with a cell surface chemokine receptor called CXCR2.

<span class="mw-page-title-main">Fascin</span> Actin bundling protein

Fascin is an actin bundling protein.

<span class="mw-page-title-main">Mucin 4</span> Protein-coding gene in the species Homo sapiens

Mucin-4 (MUC-4) is a mucin protein that in humans is encoded by the MUC4 gene. Like other mucins, MUC-4 is a high-molecular weight glycoprotein.

<span class="mw-page-title-main">KLF4</span> Protein-coding gene in the species Homo sapiens

Kruppel-like factor 4 is a member of the KLF family of zinc finger transcription factors, which belongs to the relatively large family of SP1-like transcription factors. KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer. It has three C2H2-zinc fingers at its carboxyl terminus that are closely related to another KLF, KLF2. It has two nuclear localization sequences that signals it to localize to the nucleus. In embryonic stem cells (ESCs), KLF4 has been demonstrated to be a good indicator of stem-like capacity. It is suggested that the same is true in mesenchymal stem cells (MSCs).

<span class="mw-page-title-main">TPX2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">AGR2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CDH17</span> Protein-coding gene in the species Homo sapiens

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References

  1. 1 2 3 "The Royal Society of Edinburgh: Professor Owen Sansom". Archived from the original on 2 October 2018. Retrieved 27 July 2018.
  2. 1 2 3 "The Academy of Medical Sciences: Professor Owen Sansom". Archived from the original on 2 October 2018. Retrieved 27 July 2018.
  3. 1 2 3 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. 1 2 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. 1 2 3 "Beatson Institute: Owen Sansom". Archived from the original on 28 February 2018. Retrieved 31 July 2018.
  7. 1 2 "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. 1 2 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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