Morphogenesis and Regenerative Medicine at the University of Virginia

Symposium Speakers

Dr. Paul N. Adler is Kenan Professor of Biology at the University of Virginia. Dr. Adler's research has principally been focused on planar polarity and how cells within a tissue coordinate their structure and cytoskeletons with their neighbors. Dr. Adler developed the Drosophila wing model for studying planar polarity and his early studies lead to the identification of the frizzled pathway and that it functioned to polarize all of the cells in the wing. This pathway functions in both vertebrates and invertebrates in a number of different cellular contexts to polarize cells. More recently he has focused on the role of downstream components of the frizzled pathway and on how they locally activate the cytoskeleton. This research has led to new insights into how epidermal cells produce polarized extensions, insure their integrity and on a new conserved pathway that regulates cell shape and morphogenesis.

 Dr. Kathryn Anderson is a Professor and Chair of Developmental Biology at the Memorial Sloan-Kettering Cancer Center and is a member of the National Academy of Sciences. Dr. Anderson has been a leader in discovering how signaling systems establish embryonic polarity, and she has contributed significantly to our understanding of the molecular biology and biochemistry of signaling pathways used to control animal development. Her studies also have revealed common molecular mechanisims shared between the Drosophila immune system and innate immunity in mammals. Most recently she has turned her atttention to the identification of genes that control mouse embryogeneses, developing powerful screens to identify and characterize genes that control gastrulation, early morphogenesis, and nervous system development.

 Dr. Helen Blau is a Professor of Pharmacology at the Stanford University School of Medicine and a member of the Institute of Medicine of the National Academy of Sciences. Dr. Blau has made important contributions to our understanding of how cells maintain their differentiated state, yet remain plastic and able to change. Using novel cell fusion techniques, she demonstrated that the differentiated state is remarkably plastic, even in adult tissues. Dr. Blau has provided evidence that stem cells exist in the adult that can participate in vasculogenesis, and she has extended these findings to the plasticity of stem cells involved in the derivation of CNS neurons and muscle cells. Her work has implications for cell and gene therapy, and she has developed muscle-mediated gene therapy to deliver therapeutic agents to the blood.

 Dr. Hans Clevers is a Professor and Co-director of the Hubrecht Laboratory, Netherlands Institute for Developmental Biology in Utrecht and a member of the Royal Netherlands Academy of Arts and Sciences. He began his career studying signaling in T lymphocytes and transcriptional regulation of T cell development. He then discovered that T-cell factor (TCF) is a key transcriptional mediator of the Wnt signaling pathway. Dr. Clevers has elucidated the role of this important developmental signaling pathway in the pathogenesis of colorectal cancer, demonstrating that it imposes a crypt progenitor phenotype on colorectal cancer cells. Furthermore, he discovered the role of this pathway in the morphogenesis of the intestinal epithelium, showing that it mediates cell positioning by regulating the expression of ephrins, which control the repulsive behavior of cells.

 Dr. Frank Costantini is a Professor and the Acting Chair of the Department of Genetics and Development at Columbia University College of Physicians and Surgeons. He was an early pioneer in the development of transgenic mouse technology and has directed his expertise towards discovering the molecular basis of inductive interactions during mammalian embryogenesis and organogenesis and the development of mouse models of human diseases. He discovered important genes that participate in embryonic axis specification, regulation of the Wnt signal transduction pathway, and mesenchymal-epithelia interactions during kidney organogenesis. Along with the development of transgenic mice expressing green fluorescent protein in the ureteric bud, these studies have made important contributions to understanding the process of branching morphogenesis in the developing nephron.

 Dr. Francoise Dieterlen is Directeur de Recherche emerite au CNRS. Her work focuses on the development of the hematopoietic and vascular systems. Francoise Dietelen was the first to uncover the existence of hematopoietic stem cells of intraembryonic origin, that relay yolk sac stem cells during vertebrate development. Although first demonstrated in the avian model, this rule has since been extended to amphibians, zebrafish, mouse, and man. The avian model also permitted her group to define the distribution of sites of hemangioblastic and angioblastic potential, in the splanchnopleural mesoderm and somites, respectively, and to document the developmental relationships between endothelial cells and hematopoietic stem cells. Dr. Dieterlen's present work indicates that emergence of hematopoietic stem cells during development is an ongoing process, for a longer period than previously thought.

 Dr. Mark Ferguson is a Professor in the School of Biological Sciences and member of UK Centre for Tissue Engineering at the University of Manchester, UK and the co-founder and CEO of Renovo Ltd, a biopharmaceutical company. He has begun to elucidate the molecular mechanisms regulating palate morphogenesis, identifying proteins that mediate palate fusion and prevent the development of cleft palate. He also has made fundamental discoveries about the mechanisms of wound healing, demonstrating that embryonic wounds heal without scarring. Major differences between scar-free embryonic wound healing and scar forming adult wound healing have been identified. Dr. Ferguson co-founded Renovo to develop drugs that prevent scars and accelerate wound healing in the skin. Several candidate anti-scarring molecules already have been developed and are now entering human clinical trials.

Dr. Janet Heasman is a Professor of Pediatrics and Developmental Biology at the University of Cincinnati School of Medicine. She has made major contributions to our understanding of the earliest stages of vertebrate embryogenesis, using the frog Xenopus laevis as a model system to study the molecular mechanisms by which the first tissues, ectoderm, mesoderm and endoderm, develop. She has shown that maternal molecules stored in the oocyte initiate both embryonic pattern and germ layer formation. Dr. Heasman also has pioneered the use of morpholino oligonucleotides as a new antisense approach for studies of gene function, which has been adopted by many labs. Moreover, her studies of adhesion and cytoskeletal proteins in Xenopus have provided many insights into the morphogenetic events occurring during the earliest stages of embryogenesis.

 Dr. Jeffrey A. Hubbell is Director of the Institute for Biomedical Engineering of the ETH (Swiss Federal Institute of Technology) in Zurich and Professor of Biomedical Engineering at the University of Zurich. He is a leader in the development of biomaterials for tissue engineering, cell-based therapies, drug delivery, and medical devices. His main contributions have been in polymer chemistry where he has addressed how the recognition of biological and synthetic polymers may be controlled. He has developed methods to incorporate protein-like structures into synthetic materials and to endow synthetic materials with the ability to be degraded by the cellular processes involved in tissue remodeling. Clinical targets include cardiovascular implants, nerve regeneration, post-surgical healing, and general aspects of the controlled delivery of proteins and genes.

 Dr. Garrett Odell is a Professor of Zoology at the University of Washington. He is an applied mathematician who makes and tests models of how interactions between the behaviors of molecules or cells produce the complex behavior of the ensemble. Computer solutions of the equations are used to generate computer-animated display of the emergent dynamic behavior. His models have provided important insights into several biological processes, including the morphogenetic movements of epithelial cell sheets in embryos, the way cell cycle control proteins interact to make a cell division clock, and how a network of developmental genes can form a robust module with a characteristic intrinsic behavior - permitting evolutionary change of inputs without changing intrinsic behavior. He also has created a computer-controlled microscope to record time-lapse movies of developing embryos.

 Dr. Alex Schier is an Associate Professor of Cell Biology and a member of the Developmental Genetics Program in the Skirball Institute of Biomolecular Medicine at New York University School of Medicine. He has made major inroads into the genetic analysis of patterning and morphogenesis of vertebrate embryos, using zebrafish as a model organism. He has analyzed the function of numerous genes that control the cellular mechanisms and signal transduction pathways underlying the patterning and morphogenesis of the vertebrate head. More recently Dr. Schier has begun to elucidate some of the mechanisms underlying the development of left-right asymmetry in the vertebrate body and in individual organs.

 Dr. Allan Spradling is a member of the Carnegie Institution of Washington, a Howard Hughes Medical Institute investigator, and a member of the National Academy of Sciences. Dr. Spradling uncovered mechanisms of gene amplification in development and revolutionized Drosophila genetics by discovering a method to transform Drosophila with any cloned gene using transposable elements. This technology also has permitted identification of regulatory sequences that control gene expression. More recently he has made major contributions to our understanding of stem cell regulation in the Drosophila ovary. He has identified cells that make up the niche, a specialized cellular environment that provides stem cells with the support for self-renewal, and suggests that the niche constitutes a primary regulatory mechanism capable of reprogramming somatic cells to become stem cells.

 Dr. Masatoshi Takeichi is a Professor of Cell and Developmental Biology at Kyoto University and the Director of the RIKEN Center for Developmental Biology in Kobe, Japan. Dr. Takeichi elucidated the basic mechanisms underlying the process of cell-cell adhesion in animals. He discovered the cadherin family of adhesion proteins, which mediate calcium-dependent cell-cell adhesion, and found that differential expression of cadherins contributes to selective cell adhesion through homophilic interactions. His studies on the functional roles and molecular mechanisms of the cadherin-superfamily have had great impact on the fields of developmental biology, cell biology, and oncology. Dr. Takeichi's most recent interest has been the role of cadherins in the nervous system, and he has provided evidence that cadherins contribute to the specificity of synaptic interactions and neuronal wiring.

 Dr. Eric Wieschaus is a Professor of Molecular Biology at Princeton University and a Howard Hughes Medical Institute Investigator. He also is a member of The National Academy of Sciences and a Nobel Laureate in Physiology and Medicine (1995). In his Nobel research, Dr. Wieschaus, along with Dr. Nusslein-Volhard, discovered and analyzed a large number of genes that determine segment number and polarity in Drosophila, laying the foundations for our current understanding of the signaling and transcriptional events underlying pattern formation in development of all animals. Most recently, Dr. Wieschaus has provided insights into the genetic and cellular control of embryonic morphogenesis through studies on cellularization and gastrulation in Drosophila.

Note: Photos and portions of these biosketches are excerpted from the speaker's web pages.

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