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Laura Machesky

Laura Machesky is a cell biologist

Elected Fellow of the Academy of Medical Sciences since 2016

Fellow of the Royal Society of Edinburgh, 2014

Elected a Member of the European Molecular Biology Organization, 2012

Keith R. Porter Fellowship, 2011

American Society for Cell Biology, Women in Cell Biology Junior Award, 2001

Early Life
''Watt was born on 28 March 1956 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" .''

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". 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, Notch , Wnt and receptor tyrosine kinase signalling in regulating their behavior. She identified the first marker, integrin extracellular matrix (ECM) receptors, that could be used to isolate epidermal stem cells – 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, identified different sensing mechanisms and downstream signalling pathways , and elucidated the nature of the switch between stem cells and differentiated cells.

A pioneer of single cell gene expression profiling, 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 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, bacteria and immune cells. She uncovered new mechanisms by which integrins contribute to cancer, including the first tumour-associated integrin mutation. She also identified the first Wnt-inhibitory mutation that stimulates tumour formation. 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.

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 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/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.