Fiona Watt
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Fiona Watt

Fiona Watt, (born 28 March 1956) is a British scientist who is internationally known for her contributions to the field of stem cell biology. In the 1980's, when the field was in its infancy, she highlighted key characteristics of stem cells and their environment that laid the foundation for much present day research [1]. She is currently director of the Centre for Stem Cells & Regenerative Medicine at King's College London, and Executive Chair of the MRC, the first woman to lead the MRC since its foundation in 1913 [2].

Early Life

Watt was born on 28 March 1956 [3] in Edinburgh, Scotland. Her father was a dental surgeon who combined his clinical work with an active research programme. Her family were members of the Church of Scotland, and she attributes her commitment to public service to her Presbyterian upbringing. Her younger sister, Wendy, died in 1982. Fiona Watt knew she wanted to be a scientist from a very young age. She is quoted as saying, "I think that being a scientist is in a sense hardwired, and there are people who just couldn't conceive of being anything else" [4].

Career

Fiona Watt obtained her Bachelor of Arts in Natural Sciences in 1976, and her master's degree in 1979, both at Murray Edwards College, Cambridge University. She also obtained her Doctor of Philosophy (DPhil) from the Sir William Dunn School of Pathology, University of Oxford in 1979, supervised by Henry Harris, naming her thesis "Microtubule-organizing centres in cells in culture and in hybrids derived from them" [5][6]. Watt then completed a two-year postdoctoral research position at the Massachusetts Institute of Technology (MIT), US, with Dr. Howard Green. Two of her fellow postdocs, Bruce Spiegelman and Elaine Fuchs, were to remain lifelong friends. Upon returning to the UK, she founded her first lab at the Kennedy Institute of Rheumatology in London where she became Head of the Molecular Cell Biology Laboratory. In 1987 she relocated to the Cancer Research UK London Research Institute (now part of the Francis Crick Institute) where she served as Head of the Keratinocyte Laboratory. From 2007 to 2012 she worked in Cambridge, where she helped to establish the Cambridge Cancer Research UK Institute and the Wellcome Trust Centre for Stem Cell Research. She was a Fellow of St John's College and the first Herchel Smith Professor of Molecular Genetics at Cambridge University.

Moving to King's College London in 2012, she set up the internationally renowned Centre for Stem Cells and Regenerative Medicine (CSCRM) to promote collaboration between scientists and clinicians in order to progress the potential of stem cells into clinical reality for patients. By paying equal attention to architecture, infrastructure and recruitment she has created a unique research environment where research can flourish.

Research

Fiona Watt's major research contribution has been to elucidate how the outer covering of mammalian skin, the epidermis, is maintained through self-renewal of stem cells and terminal differentiation of their progeny. Using cultured human epidermis and genetically modified mice, she pioneered the identification of stem cell populations and elucidated the roles of integrin [7], Notch [8], Wnt [9] and receptor tyrosine kinase [10]signalling in regulating their behavior. She identified the first marker, integrin extracellular matrix (ECM) receptors, that could be used to isolate epidermal stem cells [11] - researchers have subsequently found that this marker enriches for stem cells in a wide range of tissues. In addition, others have amply confirmed her original concept that the ECM is a key component of the stem cell niche.

Her lab's research has also shown that the interplay between diverse intrinsic and extrinsic signals is central to determining cell fate [12], identified different sensing mechanisms and downstream signalling pathways [13], and elucidated the nature of the switch between stem cells and differentiated cells [14].

A pioneer of single cell gene expression profiling [15], she demonstrated that different human epidermal stem cell states are not stochastic but reflect the existence of stem cell subpopulations that had not been identified previously. By demonstrating the existence of functionally distinct skin fibroblast lineages [16] she has opened the way for new strategies to treat scarring and fibrosis.

Fiona Watt's work has resulted in new insights into how epidermal deregulation leads to tumor formation, including the roles played by differentiated cells [17], bacteria and immune cells [18]. She uncovered new mechanisms by which integrins contribute to cancer, including the first tumour-associated integrin mutation [19]. She also identified the first Wnt-inhibitory mutation that stimulates tumour formation [20]. The generality of her observations has been confirmed in other solid tumours. In recent years she has become increasingly interested in the relationship between genetic variants and cellular behaviour [21].

Leadership

Fiona Watt has shown leadership in many aspects of academic life. She has played a key role in promoting UK government investment in stem cell research, for example as specialist adviser to the House of Lords Science and Technology Committee. She is past-president of the British Society for Cell Biology and the International Society for Stem Cell Research (ISSCR). She has long been passionate about scientist-led publication, serving as Editor-in-Chief of Journal of Cell Science for 20 years and then as a founding Deputy Editor of eLife. Fiona Watt is a vocal advocate for women in science. In a series of articles [22][23] and interviews with women scientists (2004-2005) she examined the struggles women face in 'getting to the top' and how personal lives shape careers. She has also written candidly about her own experiences and collaborated with the New York Stem Cell Foundation to define actionable strategies for advancing women in science, engineering, and medicine. She is active in public engagement and participates in a wide range of events, appearing regularly in the media.

At the MRC she has launched a highly successful programme to enable full-time clinicians to participate in research; worked with and engaged Black and Minority Ethnic PhD students to identify new ways to support their academic careers; and developed new initiatives in multi-morbidity, adolescent mental health and pain. Most recently she has spearheaded efforts to fund coronavirus research, helping to ensure that the first awards from UKRI/DHSC were made just as the scale of the pandemic was becoming apparent.


Awards and honours

Fiona Watt has received a number of awards and honours. She is a Member of the European Molecular Biology Organization (1999), Fellow of the Academy of Medical Sciences (2000) and a Fellow of the Royal Society (2003). She was elected an Honorary Foreign Member of the American Academy of Arts and Sciences in 2008 and was awarded the Hunterian Society Medal in 2015. She is a Doctor Honoris Causa of the Universidad Autonoma de Madrid (2016). She won the American Society for Cell Biology (ASCB) Women in Cell Biology Senior Award in 2008 and the FEBS/[[European Molecular Biology Organization |EMBO] Women in Science Award in 2016. She was elected an Honorary Member of Society for Investigative Dermatology (2018) and Honorary Fellow, British Pharmacological Society (2019). She is a Foreign Associate of the National Academy of Sciences (2019). She is a member of several advisory boards, including the European Molecular Biology Laboratory Scientific Advisory Committee and the Howard Hughes Medical Institute Medical Advisory Board.

References

  1. ^ Hall, PA; Watt, FM (1989). "Stem cells: the generation and maintenance of cellular diversity". Development. 106 (4): 619-33. PMID 2562658.
  2. ^ MRC, Medical Research Council (4 April 2018). "Professor Fiona Watt new Executive Chair of the MRC". mrc.ukri.org.
  3. ^ MRC, Medical Research Council (4 April 2018). "Professor Fiona Watt new Executive Chair of the MRC". mrc.ukri.org.
  4. ^ Lako, M; Daher, S (2009). "Balancing Work and Life: A Conversation with Fiona Watt". Stem Cells. 27 (4): 762-763. doi:10.1002/stem.53. PMC 2988410. PMID 19350675.
  5. ^ Lako, M; Daher, S (2009). "Balancing Work and Life: A Conversation with Fiona Watt". Stem Cells. 27 (4): 762-763. doi:10.1002/stem.53. PMC 2988410. PMID 19350675.
  6. ^ Watt, Fiona M. (1979). Microtubule organizing centres in cells in culture and in hybrids derived from them (Thesis). Thesis DPhil--University of Oxford.
  7. ^ Adams, JC; Watt, FM (1989). "Fibronectin inhibits the terminal differentiation of human keratinocytes". Nature. 340 (6231): 307-9.
  8. ^ Lowell, S; Jones, P; La Roux, I; Dunne, J; Watt, FM (2000). "Stimulation of human epidermal differentiation by delta-notch signalling at the boundaries of stem-cell clusters". Curr Biol. 10 (9): 491-500. doi:10.1016/S0960-9822(00)00451-6. PMID 10801437.
  9. ^ Zhu, AJ; Watt, FM (1999). "beta-catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion". Development. 126 (10): 2285-98. PMID 10207152.
  10. ^ Zhu, AJ; Haase, I; Watt, FM (1999). "Signaling via beta1 integrins and mitogen-activated protein kinase determines human epidermal stem cell fate in vitro". Proc Natl Acad Sci U S A. 96 (12): 6728-33. Bibcode:1999PNAS...96.6728Z. doi:10.1073/pnas.96.12.6728. PMC 21983. PMID 10359780.
  11. ^ Jones, PH; Watt, FM (1993). "Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression". Cell. 73 (4): 713-2. doi:10.1016/0092-8674(93)90251-K. PMID 8500165.
  12. ^ Connelly, JT; Gautrot, JE; Trappmann, B; Tan, DW; Donati, G; Huck, WT; Watt, FM (2010). "Actin and serum response factor transduce physical cues from the microenvironment to regulate epidermal stem cell fate decisions". Nat Cell Biol. 12 (7): 711-8. doi:10.1038/ncb2074. PMID 20581838.
  13. ^ Trappmann, B; Gautrot, JE; Connelly, JT; Strange, DG; Li, Y; Oyen, ML; Cohen Stuart, MA; Boehm, H; Li, B; Vogel, V; Spatz, JP; Watt, FM; Huck, WT (2012). "Extracellular-matrix tethering regulates stem-cell fate". Nat Mater. 11 (7): 642-9. Bibcode:2012NatMa..11..642T. doi:10.1038/nmat3339. PMID 22635042.
  14. ^ Mishra, A; OulEs, B; Pisco, AO; Ly, T; Liakath-Ali, K; Walko, G; Viswanathan, P; Tihy, M; Nijjher, J; Dunn, SJ; Lamond, AI; Watt, FM (2017). "A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis". eLife. 6. doi:10.7554/eLife.27356. PMC 5667932. PMID 29043977.
  15. ^ Jensen, KB; Watt, FM (2006). "Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence". Proc Natl Acad Sci U S A. 103 (32): 11958-63. Bibcode:2006PNAS..10311958J. doi:10.1073/pnas.0601886103. PMC 1567680. PMID 16877544.
  16. ^ Driskell, R; Lichtenberger, BM; Hoste, E; Kretzschmar, K; Simons, BD; Charalambous, M; Ferron, SR; Herault, Y; Pavlovic, G; Ferguson-Smith, AC; Watt, FM (2013). "Distinct fibroblast lineages determine dermal architecture in skin development and repair". Nature. 504 (7479): 277-281. Bibcode:2013Natur.504..277D. doi:10.1038/nature12783. PMC 3868929. PMID 24336287.
  17. ^ Owens, DM; Watt, FM (2001). "Influence of beta1 integrins on epidermal squamous cell carcinoma formation in a transgenic mouse model: alpha3beta1, but not alpha2beta1, suppresses malignant conversion". Cancer Res. 61 (13): 5248-54. PMID 11431366.
  18. ^ Hoste, E; Cipolat, S; Watt, FM (2015). "Understanding allergy and cancer risk: what are the barriers?". Nat Rev Cancer. 15 (3): 131-2. doi:10.1038/nrc3909. PMID 25866857.
  19. ^ Evans, RD; Perkins, VC; Henry, A; Stephens, PE; Robinson, MK; Watt, FM (2003). "A tumor-associated beta 1 integrin mutation that abrogates epithelial differentiation control". J Cell Biol. 160 (4): 589-96. doi:10.1083/jcb.200209016. PMC 2173744. PMID 12578911.
  20. ^ Takeda, H; Lyle, S; Lazar, AJ; Zouboulis, CC; Smyth, I; Watt, FM (2006). "Human sebaceous tumors harbor inactivating mutations in LEF1". Nat Med. 12 (4): 395-7. doi:10.1038/nm1386. PMID 16565724.
  21. ^ Vigilante, A; Laddach, A; Moens, N; Meleckyte, R; Leha, A; Ghahramani, A; Culley, OJ; Kathuria, A; Hurling, C; Vickers, A; Wiseman, E; Tewary, M; Zandstra, PW; HipSci, Consortium; Durbin, R; Fraternali, F; Stegle, O; Birney, E; Luscombe, NM; Danovi, D; Watt, FM (2019). "Identifying Extrinsic versus Intrinsic Drivers of Variation in Cell Behavior in Human iPSC Lines from Healthy Donors". Cell Rep. 26 (8): 2078-2087. doi:10.1016/j.celrep.2019.01.094. PMC 6381787. PMID 30784590.
  22. ^ Watt, FM (2006). "Women in cell biology: getting to the top". Nat Rev Mol Cell Biol. 7 (4): 287-290. doi:10.1038/nrm1894. PMID 16607291.
  23. ^ Watt, FM (2006). "Women in cell biology: how personal lives shape careers". Nat Rev Mol Cell Biol. 7 (5): 278-80. doi:10.1038/nrm1913. PMID 16550214.

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