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Scientific discussion meeting organised by Dr Rafael Edgardo Carazo Salas, Dr Attila Csikasz-Nagy and Dr Masamitsu Sato
This event brought together an interdisciplinary group of scientists from the UK and abroad to speak about the latest progress in the field of cell polarity research, from basic principles to medical implications. It provided a unique opportunity to bring together basic and translational scientists and the public, to discuss this important subject at a high calibre meeting.
Biographies of the organisers and speakers are available below and you can also download the draft programme (PDF). Recorded audio of the presentations are now available below and the papers have been published in an issue of Philosophical Transactions B.A related satellite meeting immediately followed this event.
Dr Rafael Carazo Salas, University of Cambridge, UKOrganiser
Dr Rafael E. Carazo Salas is group leader at the Gurdon Institute and the Department of Genetics of the University of Cambridge, and an ERC Starting Independent Researcher. Trained in physics, he did a PhD in cell biology with Eric Karsenti at EMBL Heidelberg in 2001, where his work helped identify the GTPase Ran as master regulator of mitosis. He then worked with Paul Nurse as postdoctoral fellow at Cancer Research UK in London and later as Research Associate at the Rockefeller University in New York, where his work showed that motor protein-mediated self-organization is a universal pathway of microtubule control. Since 2008 his group studies the molecular networks that regulate cell morphogenesis, using inter-disciplinary functional genomics approaches.
Dr Masamitsu Sato, University of Tokyo, JapanOrganiser
Masamitsu Sato completed his PhD in Genetics with Masayuki Yamamoto at the Graduate School of Science, University of Tokyo in 2001. He pursued postdoctoral research with Takashi Toda in Cancer Research UK, London Research institute. He focused on the relationship of the nuclear transport machinery and microtubule formation in fission yeast mitosis. In 2006, he moved back to the Masayuki Yamamoto laboratory as an assistant professor, where he started to focus on revealing the uniqueness of the cytoskeleton in meiosis. He was awarded the Young Scientists’ Prize of the Commendation for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology of Japan in 2012.
Dr Attila Csikász-Nagy, King's College London, UKOrganiser
Dr Attila Csikász-Nagy holds a Senior Lectureship at King’s College London and serves as a group leader at the Research and Innovation Centre of Fondazione Edmund Mach in San Michele all’Adige, Italy. He received a PhD in 2000 for his work on mathematical models of cell cycle regulation. He was a postdoctoral fellow at Virginia Tech (USA), an assistant professor in Hungary and a principal investigator at The Microsoft Research – University of Trento Centre for Computational Systems Biology in Italy before taking up his double appointment in Italy and the UK. His group studies the dynamics of the regulatory networks that control cell cycle, polarized cell growth and cell to cell interactions.
Professor Rong Li, Stowers Institute for Medical Research, USEstablishment and maintenance of cell polarity for asymmetric meiotic cell divisions in mouse oocytes
Mammalian oocytes undergo two rounds of asymmetric cell divisions during meiotic maturation. In in-vitro cultured oocytes, symmetry breaking occurs concurrent with migration of meiosis I spindle to a subcortical localization, whereby the meiotic chromatin induces the assembly of a polar actomyosin domain critical for the 1st polar body extrusion. Subsequently, meiosis II spindle forms at a nearby subcortical location and maintains oocyte cortical polarity in preparation for the second polar body extrusion upon fertilization. Recent studies have shown that, whereas the chromatin provides the inductive signal for oocyte cortical polarity, dynamic actin assembly at different cellular locations powers chromosome migration in meiosis I and the maintenance of spindle positioning in meiosis II. Recent progress on the mechanisms of actin-based force production and a mechanical model of cellular symmetry breaking will be presented.
Rong Li graduated from Yale College in 1988. She did her PhD thesis with Andrew Murray at UCSF where she studied the spindle assembly checkpoint. After a postdoc with David Drubin at UC Berkeley working on the regulation of the actin cytoskeleton, she took her first faculty position in 1994 in the Department of Cell Biology, Harvard Medical School. Ten years later, she moved her lab to the Stowers Institute for Medical Research. She is a cell biologist whose research interest ranges from basic mechanisms of cell polarization, cell motility, and cell division, to epithelial morphogenesis, cellular aging and genome evolution.
Professor Leah Edelstein-Keshet, University of British Columbia, USModelling the roles of small GTPases in cell polarization, and cell shape
The small GTPAses Cdc42, Rac, and Rho are signalling proteins that coordinate the assembly, disassembly, and dynamics of the actin cytoskeleton. In this way, they regulate both cell polarization, cell shape, and motility in eukaryotic cells such as neutrophils. In my talk, I will describe spatio-temporal models of small GTPases, showing how their mutual interactions and feedback can affect the ability of the cell to respond to stimuli, polarize robustly, as well as its sensitivity to new stimuli. Both detailed and simplified (abstract) models have contributed to our understanding of these phenomena. Furthermore, in studying such models, we have utilized some recently developed mathematical methods that are of wider applicability in analysis of pattern formation. I will briefly describe these methods and our results.
Leah Edelstein-Keshet has been working at the interface of biology and mathematics for over 30 years. She received her PhD in Applied Mathematics at the Weizmann Institute of Science in 1982. At UBC, she has been working on models for actin dynamics since the early 1990's, with recent interest in cell polarity, signalling, and motility since 2000. Her secondary area of interest is swarming and aggregation in social animals.
Dr Barry Thompson, London Research Institute, Cancer Research UK, UKPositive feedback and mutual antagonism in cell polarity
Epithelial tissues are composed of polarised cells with distinct apical and basolateral membrane domains. In the Drosophila ovarian follicle cell epithelium, apical membranes are specified by several apical determinants: the transmembrane protein Crumbs (Crb), its binding partner Stardust (Sdt), and the aPKC-Par6-cdc42 complex. Basolateral membranes are specified by the determinants Lgl, Dlg and Scrib. Apical and basolateral determinants are known to act in a mutually antagonistic fashion, but it remains unclear how this interaction generates polarity. We have built a computer model of apico-basal polarity which suggests that the combination of positive feedback among apical determinants plus mutual antagonism between apical and basal determinants is essential for polarisation. In agreement with this model, in vivo experiments define a positive feedback loop in which Crb self-recruits via Crb-Crb extracellular domain interactions, recruitment of Sdt and aPKC-Par6-cdc42 to the plasma membrane, aPKC phosphorylation, and recruitment of Expanded and Kibra to prevent endocytic removal of Crb from the plasma membrane. Ectopic activation of components of this loop can generate runaway positive feedback and ectopic spreading of apical determinants. Lgl antagonises the operation of this feedback loop, explaining why apical determinants do not normally spread into the basolateral domain. Once Crb is removed from the plasma membrane, it undergoes recycling via Rab11 endosomes. Our results provide a dynamic model for understanding how epithelial polarity is maintained in Drosophila follicle cells.
Professor Cécile Sykes, Institut Curie, FranceCell shape changes: quantitative role of membrane, cytoskeleton, and how they are attached
In order to unveil generic mechanisms of cell movements and shape changes, we design stripped-down experimental systems that reproduce cellular behaviours in simplified conditions, using liposome membranes on which the cytoskeleton is attached. Such stripped-down systems allow for a controlled study of the physical mechanisms that underlie cell movements and cell shape changes. Moreover, these experimental systems are used to address biological issues within a controlled, simplified environment.We have reconstituted the actin cortex of cells inside liposomes, and used it as a simplified system to study endocytosis. We will present our work on reconstituted actin cortices at the membrane of liposomes, and a characterization of their mechanical properties measured by tube pulling, and liposome spreading, as done previously in cells. We will show how these cortices contract in the presence of myosin motors, and how such experiments shed light of the mechanisms of cell shape changes.
Cécile Sykes is the author of about 50 publications in international journals. She is a CNRS researcher, and a professor at the Ecole Polytechnique in France. Trained as a solid state physicist (PhD in Semiconductor Physics), Cécile Sykes got interested gradually in Soft Matter Physics and in Biophysics. She founded the group “Biomimetism of Cellular Movements” in 2001 at the Curie Institute that aims at designing and studying biomimetic systems for a understanding cell motility and cell shape changes. This group has developped actin-based motility systems, beads, droplets and liposomes propelled in cell extracts or purified proteins. Now the activity of the group is dedicated to cell mimicking liposomes that reprocuce cell shape changes by actin polymerization mimicking endocytosis, or contraction through the action of molecular motor like myosin and actin. The motivation of this work is to understand how cells move and change shape in a disease like cancer.
Professor Daniel Lew, Duke University, USInteraction between bud-site-selection and polarity-establishment machineries in budding yeast
Yeast cells polarize and form a single bud in each cell cycle. Genetic approaches have identified the molecular machinery responsible for positioning the bud site. Immobile landmark proteins, deposited at specific locations during bud formation, act after cytokinesis to promote activation of the conserved Rho-family GTPase, Cdc42, in their vicinity. Cdc42 accumulates further by positive feedback, creating a concentrated patch of GTP-Cdc42 at the bud site. Using high-resolution imaging and mathematical modeling, we examined the process of bud-site establishment. Polarity factors sometimes accumulated at more than one of the landmark-specified locations, and we suggest that competition between clusters of polarity factors determines the final bud location. Modeling indicated that competition would be impaired by continuing landmark-localized activity, and we suggest that polarity factors terminate landmark activity to preclude such interference. Imaging reveals unexpected effects of the bud-site-selection system on the dynamics of polarity establishment, raising new questions about how that system may operate.
Danny Lew first trained in genetics (BA), then in molecular biology (as a PhD student with James Darnell, working on interferon-stimulated transcription), and then in yeast genetics and cell biology (as a postdoc with Steve Reed, working on cell cycle control). He is currently a Professor in the Department of Pharmacology and Cancer Biology at Duke University, where his work focuses on a new cell cycle checkpoint in yeast, which his laboratory discovered and called the morphogenesis checkpoint. He also studies polarity establishment, with a view to understanding the universal problems of symmetry breaking and singularity (i.e., why a polarized cell has one and only one “front”). Recently, his laboratory has started combining mathematical modeling with standard genetics/biochemistry/cell biology approaches to understand the design principles of the polarity and vesicle trafficking machinery.
Dr W. James Nelson, Stanford University, USEvolution of Epithelial Organization and the Cadherin-Catenin Complex
A tube surrounded by a simple epithelium is the most basic tissue organization in metazoans. Epithelial tubes are formed by actomyosin-based constriction of the apical surface of epithelial sheets. In higher animals, epithelial organization is maintained by cadherin adhesion proteins which bind -catenin and -catenin that in turn organizes the actin cytoskeleton. I will discuss recent structure/function studies of the catenin complex in a variety of organisms. The results show that the catenin complex plays remarkably conserved functions in the formation and functional organization of epithelial structures from mammals to slime molds.
My research over the last 30 years has sought to understand how cell-cell interactions specify the correct cellular organization of complex tissues, and how structurally and functionally different plasma membrane domains are assembled and tailored to specific tissue and organ functions. My work seeks to identify molecular mechanisms linking cell-cell adhesion to the development of structural and functional polarity of epithelial cells, a process critical for tissue development and homeostasis. I uncovered proteinprotein interactions between the cell adhesion protein E-cadherin, the membranecytoskeleton, membrane proteins (e.g., Na/K-ATPase), and complexes specifying vesicle trafficking to cell-cell contacts. My work has also defined mechanisms that initiate cellcell adhesion, and has uncovered new mechanisms important in mediating changes in actin and membrane dynamics during cell-cell adhesion. My recent studies revealed that these mechanisms are evolutionarily conserved from the slime mold to vertebrates.
Professor Norbert Perrimon, Harvard Medical School and Howard Hughes Medical Institute, USAMolecular organization of polarized domains of epithelial cells
Epithelial cells are polarized by the concerted activity of a conserved set of polarity proteins. To understand how these proteins establish and maintain distinct membrane domains we screened for downstream effectors using a library of shRNA constructs, which permit the analysis of nearly protein-null embryos by knockdown of a gene’s maternal and zygotic expression. One of our hits encodes a previously uncharacterized protein which contains a RhoGEF domain and interacts with the small GTPase Rac. This novel protein is localized to the apical cell cortex where it binds the polarity determinants Par-3 and aPKC, suggesting a role in directing Rac activity to the apical cortex. In addition, to define the molecular organization of the polarized domains in epithelial cells, we are developing a method for spatially resolved proteomics in Drosophila. Our approach uses a promiscuous labeling enzyme to catalyze the covalent labeling of all nearby proteins in a nanometer-scale radius. In this way, any subcellular region accessible to genetic targeting should become amenable to proteomic mapping.
Dr Perrimon is Professor of Genetics at Harvard Medical School, an Investigator of the Howard Hughes Medical Institute and an Associate Member of the Broad Institute . He has 30 years of experience in the fields of developmental genetics, signal transduction and genomics. His group developed many methods that have significantly improved the Drosophila toolbox. Currently, his laboratory is applying large-scale RNAi and proteomic methods to obtain a global understanding of the structure of a signaling pathways and their cross-talks. In addition, he is studying the roles of signaling pathways in homeostasis and tissue remodeling in Drosophila muscles and gut stem cells. Dr Perrimon has trained more than 80 students and postdoctoral fellows, with most of them currently holding academic positions.
Professor Orion Weiner, University of California, San Francisco, USNew tools for unlocking cell polarity
Neutrophils are innate immune cells that use directed migration to hunt and kill bacteria. This directed migration depends on several fundamental signaling capabilities. Neutrophils can migrate up chemotactic gradients spanning several orders ofmagnitude, requiring signaling adaptation so that cells respond to relative changes rather than steady-state concentrations of ligand. Neutrophils generate a consistent internal polarity that does not depend on the steepness of the external gradient, requiring positive feedback to amplify subtle signaling asymmetries and long-range inhibition so that protrusions can compete with one another to generate a dominant leading edge. Because the overall process of polarity is highly complex, we have developed (optogenetic and other) tools to isolate and dissect individual steps in the signaling cascade to better understand the overall signaling circuit. We find that plasma membrane tension orchestrates long-range inhibition, and actin dynamics are essential for adaptation.
Dr Weiner's lab is focused on developing methods for unraveling how complex biological systems function. His primary interest lies in understanding the signaling circuits that organize cell polarity. As a graduate student with Henry Bourne and John Sedat at UCSF, Dr Weiner helped delineate where gradient amplification occurs during neutrophil polarization. As a postdoc with Marc Kirschner and Lew Cantley at Harvard Medical School, Dr Weiner discovered a Rac / PIP3/actin positive feedback loop that plays a central role in generating neutrophil polarity. He also discovered that the actin assembly machinery in neutrophils is a dynamic excitable medium. Dr Weiner joined the faculty at the University of California at San Francisco in 2005 where he has been developing optogenetic tools to interrogate cell signaling and has also been investigating the mechanistic basis of cell polarity in neutrophils.
Professor Asako Sugimoto, Tohoku University, JapanAssembly of female meiotic spindles that mediate extreme asymmetric divisions
Female meiosis is an extreme case of asymmetric cell division. A primary oocyte undergoes two rounds of meiotic divisions (meiosis I and II), which produce one large egg that inherits the majority of cytoplasm, while extruding two small polar bodies. These highly asymmetric divisions are mediated by meiotic spindles formed near the oocyte cortex. Unlike mitotic spindles that are formed with microtubules nucleated from centrosomes, female meiotic spindles in many animals are formed independently of centrosomes because centrosomes are eliminated during oogenesis. How and where microtubules are formed in oocytes and how they are assembled into meiotic spindles are not well understood. To elucidate the meiotic spindle assembly mechanism, we have been using C. elegans as a model system. We will discuss how distinct microtubule assembly pathways are used in mitosis and female meiosis.
Asako Sugimoto earned her Ph.D. from the University of Tokyo, Japan in 1992, and then worked as a postdoctoral fellow in Joel Rothman’s laboratory in University of Wisconsin-Madison from 1992 to 1996, where she started using the nematode C. elegans as a model system. After returning to Japan, she worked as an Assistant Professor in the University of Tokyo and moved to RIKEN Center for Developmental Biology to take a position of Team Leader in 2001. Since 2010, she has served as Professor at the Graduate School of Life Sciences at Tohoku University. Her group currently uses C. elegans to study the mechanisms underlying dynamic cellular events in embryogenesis, such as cell polarity establishment, cell division, and morphogenesis.
Professor Geraldine Seydoux, John Hopkins University, USBreaking symmetry: Polarization of the C. elegans zygote
We will discuss the molecular mechanisms that initiate and maintain polarity in the C. elegans zygote.
Geraldine Seydoux obtained her PhD in 1991 from Princeton University with Iva Greenwald. She did her post-doctoral training at the Carnegie Institution of Washington with Andy Fire before joining the faculty at the Johns Hopkins University School of Medicine in 1995. In 1999, she was awarded a Presidential Early Career Award for Scientists and Engineers from the National Institutes of Health, and in 2001 she received a MacArthur Fellowship from the John D. and Catherine T. MacArthur Foundation. She was appointed an investigator of the Howard Hughes Medical Institute in 2005.
Professor Daniel St Johnston, University of Cambridge, UKEpithelial polarity and spindle orientation
Simple epithelia are formed of a single layer of cells that adhere to each other to form barriers between compartments or the inside and outside of the organism. Epithelial cells divide with their mitotic spindles oriented in the plane of the epithelium, so that both daughters remain within the epithelial sheet, which is important for the maintenance of epithelial integrity. Furthermore, defects in spindle orientation have been proposed to contribute to tumorogenesis by producing daughter cells outside the epithelial sheet, leading to hypertrophy or metastasis. We have used the Drosophila follicular epithelium to investigate how the spindle is aligned perpendicular to the apical-basal axis of the cell. Our results reveal that spindle orientation does not require apical, junctional or basal cues, as previously proposed, and depends instead on a novel spindle orientation pathway. We have also disrupted spindle orientation to investigate the consequences of misoriented divisions on epithelial organisation.
Daniel St Johnston spent his early career analysing the first asymmetries in development that polarize the body axes in Drosophila. This has led him to investigate how cells become polarised, how polarity controls the organisation of the cytoskeleton and how the polarised cytoskeleton is used to target components to the correct place in the cell. Much of his current work focuses on the development of apical-basal polarity in epithelial cells and how cortical polarity factors control spindle orientation, polarized secretion and the positioning of intercellular junctions in absorptive and secretory epithelia. Daniel received his B.A. from Cambridge and his Ph. D from Harvard. After a post-doc with Christiane Nüsslein-Volhard, he returned to the University of Cambridge as a Wellcome Trust Senior and then Principal Fellow at the Wellcome Trust/Cancer Research UK Gurdon Institute. He is Professor of Developmental Genetics and has been Director of the Gurdon Institute since 2009.
Dr Ian Macara, Vanderbilt University, USPolarity Proteins, Morphogenesis and Metastasis
Most human cancers arise from epithelial cells or their progenitors. Epithelial cells possess a distinctive apical-basal polarity, and loss of polarity is frequently assumed to be a common feature of cancer progression. However, there has been little experimental evidence for any role of the polarity machinery in tumor suppression. To address this issue we depleted the Par3 polarity gene by RNAi in combination with oncogenic Notch or Ras61L expression in the murine mammary gland. Par3 silencing dramatically reduced tumor latency in both models, increased tumor growth, and produced metastatic tumors that retained epithelial marker expression. Par3 depletion was associated with induction of MMP9, destruction of the extracellular matrix, and invasion, all mediated by atypical PKC-dependant JAK/Stat3 activation. Loss of Par3 also activated the Rac GTPase, which was essential for driving tumor growth. Importantly, Par3 expression is significantly reduced in human breast cancers, which correlates with active aPKC and Stat3. These data identify Par3 as a regulator of signaling pathways relevant to invasive breast cancer.
Dr Ian Macara received his PhD from the University of Sheffield, UK, then spent 3 years in Kenya as a Lecturer at the University of Nairobi, after which he moved to the United States. He received postdoctoral training with Lewis Cantley at Harvard University, working on erythroid differentiation. He became an assistant professor in Biophysics at Rochester University, and moved in 1991 to the University of Vermont, where he was a Professor in the department of Pathology. During 1997 he was a visiting Miller Professor at UC Berkeley. He subsequently moved to the University of Virginia School of Medicine, where he was a member of the Center for Cell Signaling, a Craig Scholar in the Cancer Center, Director of the Advanced Microscopy Facility, and Professor of Microbiology. He was given the University of Virginia Distinguished Scientist Award and became a Harrison Distinguished Professor. Last summer he moved to Vanderbilt University to take the Chair of the Department of Cell and Developmental Biology.
Professor Anne Ridley, King's College London, UKPolarized migration of leukocytes and cancer cells across the endothelium
In multicellular organisms, cells are constantly moving from one place to another. This cell migration is essential during development of the organism as well as maintenance of tissues in the adult. Cells of the immune system migrate out of the blood stream to fight infections and help repair wounds. Cell migration also contributes to the development of cancer. During cancer progression, cancer cells invade and migrate through the tissues and enter and then exit the blood stream to form secondary tumours, known as metastases. We are investigating how leukocytes and cancer cells attach to and cross the endothelial cells lining blood vessels. I will describe how we have identified specific proteins inside cells and on the surface of cells that are needed for leukocytes and cancer cells to interact with endothelial cells, and how reducing the expression of these proteins can decrease their transendothelial migration.
Anne Ridley obtained her BA in Natural Sciences (Biochemistry) from the University of Cambridge. She obtained her PhD in 1989 (University of London), for her research project with Hartmut Land at Imperial Cancer Research Fund (now Cancer Research UK). She was awarded an EMBO postdoctoral fellowship to visit the laboratory of David Page (Whitehead Institute, Cambridge, MA) for a year. She then moved back to the Institute for Cancer Research, London, to work as a postdoctoral fellow with Alan Hall. During this time, she discovered the roles of the Rho and Rac GTPases in regulating the actin cytoskeleton. In 1993 she started her laboratory at the Ludwig Institute for Cancer Research (University College London Branch). She became Professor of Cell Biology at University College London in 2003, and moved to King’s College London in 2007.
Professor Inke Näthke, University of Dundee, UKCell and tissue polarity in the intestinal tract
Cell and tissue polarity are tightly coupled and are vital for normal tissue homeostasis. Changes in cellular and tissue organisation are common to even early stages of disease, particularly cancer. The digestive tract is the site of the second most common cause of cancer deaths in the developed world. The epithelium that gives rise to tumours in this tissue displays a number of axes of cell and tissue polarity. Changes in cell and tissue polarity in response to genetic changes that are known to underpin disease progression provide clues about the link between molecular, cellular and tissue based mechanisms that accompany cancer. Mutations in APC are common to most colorectal cancers in humans and are sufficient to cause tumours in mouse intestine. Tissue organoids mimic many of features of whole tissue and permit identifying changes at different times after inactivation of APC. In gut tissue organoids polarity is lost very early during cancer progression while cell polarity, at least apical – basal polarity is maintained and only changes at later stages. These observations reflect the situation in tumours and validate tissue organoids as a useful system to investigate the relationship between cell polarity and tissue organisation.
Professor Inke Näthke obtained her PhD at the University of California San Francisco and did postdoctoral work at Stanford University and Harvard Medical School before joining the faculty at the University of Dundee where she is currently the Professor of Epithelial Biology in the Division of Cell and Developmental Biology. Her research aims to understand the earliest changes in gut tissue that accompany initiation and progression of tumours. Work in her laboratory uses of a variety of experimental systems and techniques from single cells to whole tissue, and isolated proteins to high-resolution imaging of normal and tumour tissue.
Dr Sandrine Etienne-Manneville, Institut Pasteur, FranceDynamics of intercellular contacts during collective cell migration
Collective cell migration is essential during development as well as in adult organisms where it participates, for instance, in tissue renewal, wound healing or cancer invasion and metastasis. As cells migrate collectively, intercellular junctions maintain the integrity of the cell monolayer while allowing differential movement and rearrangements of adjacent cells. In astrocytes, intercellular contacts are mainly formed by N-cadherin-mediated adherens junctions. Downregulation of N-cadherin is frequently observed in astrocyte derived tumors, gliomas and lead to the perturbation of cell polarity and to an increased cell velocity. To understand how cells can maintain stable intercellular junctions and simultaneously rearrange them to accommodate cellular displacement, we have investigated N-cadherin dynamics during astrocyte collective migration. We show adherens junctions undergo a continuous retrograde movement compensated by a polarized recycling of N-cadherin from the rear to the leading edge. Such dynamics allows the cells to maintain stable contacts while permitting changes of cellular interactions. In glioma cells, N-cadherin dynamics and consequently the maintenance of cell-cell contacts are perturbed leading to loss of cell polarity and to increased migration.
Sandrine Etienne-Manneville is Directrice de Recherche at the CNRS and part-time professor at Ecole Polytechnique (Palaiseau, France). She studied cell Biology and biochemistry at the Ecole Normale Supérieure in Paris and obtained her PhD in Immunology in 1998, working on the regulation of leukocyte infiltration in the central nervous system. After four years of postdoctoral fellowship in the laboratory of Prof A.Hall at the MRC-LMCB in London, she entered the CNRS as a member of D. Louvard’s team at the Curie Institute (Paris, France) in 2003. In 2006, she moved to the Pasteur Institute (Paris, France) to become an independent group leader. The 5-year group “Cell Polarity and Migration, she initiated has recently been as promoted as a Pasteur Unit “Cell Polarity, Migration and Cancer”.
Dr Elaine Fuchs, Rockefeller University, USHow Polarity Functions in Regulating Skin Stem Cell Behavior
Embryonic epidermis begins as a single layer of unspecified progenitors. During development, it receives external cues to undergo a series of morphogenetic events which culminate in the production of a stratified tissue replete with hair follicles. Postnatally, these tissues undergo self-renewal which requires stem cells. Stem cells exist both in the innermost (basal) layer of the epidermis, at the base of the sebaceous gland and in the hair follicle, in a region known as the bulge. How stem cells develop and how they balance self-renewal and differentiation is of fundamental importance to our understanding of normal tissue maintenance and wound repair. Using skin as our paradigm, we’ve been dissecting how extrinsic signaling to stem sets off a cascade of changes in transcription that governs the activation of stem cells during tissue development, homeostasis and hair cycling. Our findings have provided us with new insights into our understanding of the process of stem cell activation, and in so doing have revealed mechanisms which are also deregulated in a variety of different human cancers. In this talk, I will review some of our studies that implicate specific signaling pathways in regulating stem cell polarity and function.
Elaine Fuchs is the Rebecca C. Lancefield Professor in Mammalian Cell Biology and Development at The Rockefeller University. She is also an Investigator, Howard Hughes Medical Institute. Fuchs has published >280 papers and is internationally known for her research in skin biology, its stem cells and its associated human genetic disorders, which include skin cancers. Fuchs’ current research focuses on the molecular mechanisms that underlie how multipotent stem cells of the skin are able to both self-renew long-term and to maintain and regenerate the epidermis, sebaceous glands and hair follicles. She is interested in how stem cells respond to signals from their neighbors, adjust their program of gene expression and adopt specific fates. In addition to elucidating how these pathways are regulated in normal homeostasis, Fuchs’ team also investigates the mobilization of stem cells in wound repair and the abnormalities in the process that lead to human skin cancers. In her presentation, she will touch on her latest work on these fronts. Fuchs received her Ph.D. in Biochemistry from Princeton University, and after her postdoctoral research with Dr. Howard Green at the Massachusetts Institute of Technology, she joined the faculty at the University of Chicago in 1980. She stayed there until 2002 when she relocated to The Rockefeller University. Fuchs’ past awards and honors include the Presidential Young Investigator Award, the Richard Lounsbery Award from the National Academy of Sciences, the Novartis-Drew Award for Biomedical Research, the Dickson Prize in Medicine, the FASEB Award for Scientific Excellence, the Beering Award, the National Medal of Science, the L’Oreal-UNESCO Award and Charlotte Friend Memorial Award from the American Association for Cancer Research. In 2011, she received the Madison Medal, the Passano Award and the Albany Prize, and in April, 2012 she received the March of Dimes Prize. Fuchs is an elected member of the National Academy of Sciences, the Institute of Medicine of the National Academy of Sciences, the American Academy of Arts and Sciences, the American Philosophical Society and the European Molecular Biology Organization (foreign member). She holds honorary doctorates from Mt. Sinai/New York University School of Medicine and from the University of Illinois, Champaign-Urbana. Fuchs is also a past President of the American Society of Cell Biology, past-President of the International Society for Stem Cell Research and is on the Board of Governors of the New York Academy of Sciences. She has trained over 100 postdocs and 25 graduate students, many of whom are now at major Universities around the world.
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