Fiona Watt | |
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Born | 28 March 1956 |
Alma mater | |
Spouse(s) | Jim Cuthbert Smith |
Awards | |
Website | http://www.wattlab.org |
Fiona Watt, FRS FMedSci (born 28 March 1956) is a British scientist who is internationally known for her contributions to the field of stem cell biology. [1] In the 1980s, 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. [2] She is currently director of the Centre for Stem Cells & Regenerative Medicine at King's College London, and Executive Chair of the Medical Research Council (United Kingdom) (MRC), the first woman to lead the MRC since its foundation in 1913. [3] On 13 July 2021 she was appointed as the new Director of the European Molecular Biology Organization (EMBO). [4]
Watt was born on 28 March 1956 [5] 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. Her younger sister, Wendy, died in 1982. Fiona Watt knew she wanted to be a scientist from a very young age. [6]
Watt obtained her Bachelor of Arts degree in Natural Sciences in 1976, and her master's degree in 1979, both at Murray Edwards College, University of Cambridge. She also obtained her Doctor of Philosophy degree from the Sir William Dunn School of Pathology, University of Oxford in 1979, supervised by Henry Harris with a thesis on Microtubule-organizing centres in cells in culture and in hybrids derived from them'. [7] [6]
After her PhD, Watt completed a two-year postdoctoral research positions at the Massachusetts Institute of Technology (MIT), US, with Dr. Howard Green. 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.
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, [8] Notch, [9] Wnt [10] and receptor tyrosine kinase [11] signalling in regulating their behavior. She identified the first marker, integrin extracellular matrix (ECM) receptors, that could be used to isolate epidermal stem cells [12] – 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, [13] identified different sensing mechanisms and downstream signalling pathways, [14] and elucidated the nature of the switch between stem cells and differentiated cells. [15]
A pioneer of single cell gene expression profiling, [16] 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 [17] 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, [18] bacteria and immune cells. [19] She uncovered new mechanisms by which integrins contribute to cancer, including the first tumour-associated integrin mutation. [20] She also identified the first Wnt-inhibitory mutation that stimulates tumour formation. [21] 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. [22]
Watt 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 served 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 [23] [24] and interviews with women scientists (2004-2005) she examined the struggles women face in 'getting to the top'.
At the Medical Research Council she launched a 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. In 2020, Watt 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. During Watt’s tenure as MRC Executive Chair, she oversaw the decision to close the Mammalian Genetics Unit. This strategic decision was decried by over 150 researchers and leading geneticists internationally, including Elizabeth Fisher and Robin Lovell-Badge. [25] Following a Strategic Review in 2019, the MRC Council concluded that in light of scientific advances to create more complex clinically-related mouse models, it was timely to focus on new investments on targeted programmes that are integrated with human disease modelling. Professor Owen Sansom was appointed Director of the new National Mouse Genetics Network. [26] [27] The Medical Research Council invested more than £20 million [28] in the network bringing together a package of challenge-focused research clusters distributed across the UK and a long term partnership with the Mary Lyon Centre at Harwell. [29] [30] In December 2020 a whistleblowing investigation was triggered by UK Research and Innovation (UKRI) to investigate claims that Watt had acted in a bullying manner. [31] The investigation was completed in May 2021 and concluded there was a need to take action against Watt. UKRI said it accepted the investigation’s findings and that "appropriate action has been taken". Watt offered written apologies for her behavior to multiple individuals. [31]
Following the whistleblowing investigation, Watt remained in post until her current term as MRC Executive Chair ended in early 2022. She then took up her new position as director of the European Molecular Biology Organization. [31] As a result of the outcome of this whistle blowing investigation, in December 2021 Watt was blocked from applying to the biomedical research funder Wellcome for 12 months and is required to hand over management of her existing grants to colleagues. [32]
Watt 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/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 (EMBL) Scientific Advisory Committee (SAC) and the Howard Hughes Medical Institute Medical Advisory Board. She won the inaugural Suffrage Science award in 2011. [33]
The Medical Research Council (MRC) is responsible for co-coordinating and funding medical research in the United Kingdom. It is part of United Kingdom Research and Innovation (UKRI), which came into operation 1 April 2018, and brings together the UK's seven research councils, Innovate UK and Research England. UK Research and Innovation is answerable to, although politically independent from, the Department for Business, Energy and Industrial Strategy.
Oct-4, also known as POU5F1, is a protein that in humans is encoded by the POU5F1 gene. Oct-4 is a homeodomain transcription factor of the POU family. It is critically involved in the self-renewal of undifferentiated embryonic stem cells. As such, it is frequently used as a marker for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will cause differentiation of the cells.
The epidermal growth factor receptor is a transmembrane protein that is a receptor for members of the epidermal growth factor family of extracellular protein ligands.
Elaine V. Fuchs is an American cell biologist famous for her work on the biology and molecular mechanisms of mammalian skin and skin diseases, who helped lead the modernization of dermatology. Fuchs pioneered reverse genetics approaches, which assess protein function first and then assess its role in development and disease. In particular, Fuchs researches skin stem cells and their production of hair and skin. She is an investigator at the Howard Hughes Medical Institute and the Rebecca C. Lancefield Professor of Mammalian Cell Biology and Development at The Rockefeller University.
Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.
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).
SRY -box 2, also known as SOX2, is a transcription factor that is essential for maintaining self-renewal, or pluripotency, of undifferentiated embryonic stem cells. Sox2 has a critical role in maintenance of embryonic and neural stem cells.
Integrin beta-5 is a protein that in humans is encoded by the ITGB5 gene.
Alpha-7 integrin is a protein that in humans is encoded by the ITGA7 gene. Alpha-7 integrin is critical for modulating cell-matrix interactions. Alpha-7 integrin is highly expressed in cardiac muscle, skeletal muscle and smooth muscle cells, and localizes to Z-disc and costamere structures. Mutations in ITGA7 have been associated with congenital myopathies and noncompaction cardiomyopathy, and altered expression levels of alpha-7 integrin have been identified in various forms of muscular dystrophy.
T-box transcription factor TBX3 is a protein that in humans is encoded by the TBX3 gene.
Gail Roberta Martin is an American biologist. She is professor emerita in the Department of Anatomy, University of California, San Francisco. She is known for her pioneering work on the isolation of pluripotent stem cells from normal embryos, for which she coined the term ‘embryonic stem cells’. She is also widely recognized for her work on the function of Fibroblast Growth Factors (FGFs) and their negative regulators in vertebrate organogenesis. She and her colleagues also made valuable contributions to gene targeting technology.
Stem cell markers are genes and their protein products used by scientists to isolate and identify stem cells. Stem cells can also be identified by functional assays. Below is a list of genes/protein products that can be used to identify various types of stem cells, or functional assays that do the same. The initial version of the list below was obtained by mining the PubMed database as described in
Penelope "Penny" Jeggo is a noted British molecular biologist, best known for her work in understanding damage to DNA. She is also known for her work with DNA gene mutations. Her interest in DNA damage has inspired her to research radiation biology and radiation therapy and how radiation affects DNA. Jeggo has almost 170 publication that pertain to DNA damage, radiation, and cancer research and has received 3 top science awards/medals for her research. Jeggo has also been a member of several organizations that pertain to radiation biology; these organizations include Committee on Medical Aspects of Radiation in the Environment (COMARE), National Institute for Radiation Science laboratory researcher, and the Multidisciplinary European Low Dose Initiative (MELODI). Not only is Jeggo a member of these prestigious organizations, but she is also an editor for several publication journals that are related to cancer and radiation biology. Jeggo is very passionate towards all her research and in an interview with Fiona Watt claimed that “Although my results contributed only the tiniest smidgeon to scientific knowledge, I gained immense satisfaction from it”.
Dame Amanda Gay Fisher is a British cell biologist and Director of the Medical Research Council (MRC) London Institute of Medical Sciences at the Hammersmith Hospital campus of Imperial College London, where she is also a Professor leading the Institute of Clinical Sciences. She has made contributions to multiple areas of cell biology, including determining the function of several genes in HIV and describing the importance of a gene's location within the cell nucleus.
Ketan Jayakrishna Patel is a British-Kenyan scientist who is Director of the MRC Weatherall Institute of Molecular Medicine and the MRC Molecular Haematology Unit at the University of Oxford. Until 2020 he was a tenured principal investigator at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB).
Pleasantine Mill is a cell biologist and group leader at the MRC Human Genetics Unit at the University of Edinburgh. She won the 2018 British Society for Cell Biology Women in Cell Biology Early Career Medal.
Kairbaan Hodivala-Dilke, FMedSci is an English cell biologist who has made significant contributions to the understanding of the cellular and molecular biology of the tumour microenvironment and in particular angiogenesis. She is Professor of Angiogenesis and the Tumour Microenvironment and Deputy Institute Director of Barts Cancer Institute, Queen Mary University of London. In 2015 she was awarded the Hooke medal from the British Society for Cell Biology and EMBO membership.
Cédric Blanpain is a Belgian researcher in the field of stem cells. He is a tenured professor of developmental biology and genetics at Université Libre de Bruxelles and director of the stem cell and cancer lab at its Faculty of Medicine. He was one of the first researchers in the world to use cell lineage tracing in cancer research and he showed for the first time the existence of cancer stem cells in solid tumors in vivo. He was selected by Nature as one of 10 People who mattered most in 2012 and he received the outstanding young investigator award of the International Society for Stem Cell Research.
Elizabeth Patton, Ph.D FRSE is professor of chemical genetics and group leader of Medical Research Council Institute for Genetics and Molecular Medicine (IGMM) Human Genetics Unit in Edinburgh, Personal Chair of Melanoma Genetics and Drug Discovery for a disease which kills 20,000 Europeans a year, and accounts for 80% of all skin cancer deaths. Her research into the genetic models and drug interactions testing, sharing international findings, is mainly using zebrafish in conjunction with the Edinburgh Cancer Research Centre. She holds a number of academic leadership roles in UK, Europe and international scientific bodies.
Maddy Parsons is a British cell biologist who is a professor and Associate Dean for Impact & Innovation at King's College London. She is the Director of the Nikon Imaging Centre. Her research looks to understand the fundamental mechanisms that underpin cell adhesion and migration. She is Chair of the Medical Research Council Molecular & Cellular Medicine Board.