Abstract: The lung is made up of a tree-like system of branched airway tubes leading into millions of tiny air sacs or alveoli for gas exchange. The conducting airways and alveoli contain distinct populations of stem and progenitor cells that have tremendous potential for reparative proliferation and differentiation after damage to the epithelium, with responses varying substantially depending on the type of injury sustained. The mouse stem cell populations include Trp63+ Krt5+ basal cells in the larger airways and Type2 (AT2) cells in the alveoli. We have developed 3D organoid assays for identifying factors and pathways that promote the self-renewal and differentiation of these basal and AT2 cells. We have also identified Grainyheadlike2 (Grhl2) as a transcription factor that co-ordinates basal cell differentiation, polarity and morphogenesis during regeneration of the mucociliary airway epithelium, and have used Crispr/cas9 genome editing to identify the function of potential downstream targets.
Bio: Brigid Hogan, PhD, FRS is the George Barth Geller Professor and Chair of the Department of Cell Biology, Duke University Medical Center. She completed her undergraduate and graduate training at the University of Cambridge, UK, obtaining her PhD in 1968. She subsequently did postdoctoral research in the Department of Biology, MIT and then moved back to the UK. She held appointments in London at the Imperial Cancer Research Fund and then at the MRC National Institute for Medical Research. In 1988 she was appointed Professor of Cell Biology at Vanderbilt University Medical School and was an Investigator of the HHMI there from 1993 until 2002 when she moved to her current position at Duke Medical School.
Hogan has made many innovative contributions to the fields of mammalian embryology and the early development (morphogenesis) of complex organ systems such as the eye, kidney, heart and lungs. Her laboratory was among the first to apply techniques of molecular biology to study mouse development, initially working on genes encoding extracellular matrix proteins and later on Hox and Fox developmental transcription factors and members of the TGFbeta and BMP families of growth factors. In 1983 she initiated the Cold Spring Harbor Course “Molecular Embryology of the Mouse”. Through this course and the first edition of the CSH manual entitled "Manipulating the Mouse Embryo", Hogan and her colleagues Frank Costantini and Liz Lacy helped to make the techniques of mammalian developmental genetics and experimental embryology available to a very wide audience.
Hogan’s lab has also done innovative work in the field of stem cell biology. She made the key discovery that pluripotential stem cell lines can be derived from mouse primordial germ cells, providing the basis for one method for deriving human pluripotential stem cell lines. Most recently she has identified different epithelial stem cell populations in the adult lung and has shown how they contribute to tissue maintenance and repair after injury. This work has opened up new ways of thinking about the origin and progression of some serious respiratory disorders.
Hogan is Past-President of both the American Society for Developmental Biology and the American Society of Cell Biology. Her service to the scientific community has included being a member of the National Advisory Council of the National Institute of Child Health and Human Development, Co-Chair for Science of the 1994 NIH Human Embryo Research Panel and a member of the 2001/2002 National Academies Panel on Scientific and Medical Aspects of Human Cloning. Hogan is a Fellow of the Royal Society of London and the American Academy of Arts and Sciences and a member of the Institute of Medicine and the National Academy of Sciences, USA.