Brigid L.M. Hogan, Ph.D., FRS

M.A. (Natural Sciences) Cambridge, UK
Ph.D. (Biochemistry) Cambridge, UK
Postdoctoral, M.I.T. Cambridge, U.S.A.

University Program in Genetics
University Program in Cell & Molecular Biology
Graduate Program in Cancer Biology
Developmental Biology Training Program

Professor and Chair, Department of Cell Biology

    Research in the Hogan lab is focused on the basic mechanisms underlying organogenesis and tissue repair, and how these two processes involve stem cells. We study the development, maintenance, and repair of the foregut and lung, using the mouse as a model genetic organism. We are driven by both curiosity and by practical considerations. We believe that in the long run knowledge about changes in cell behavior, signaling pathways and genetic programs that control the growth and development of the lung and foregut can provide insights into clinically relevant problems. These include ways of promoting the maturation of the lung in premature babies, repairing the lung epithelium after injury, inhibiting the growth of tumors, and understanding the origin of birth defects such as tracheoesophageal fistula.

    We have focused on the lung for a number of reasons. First, its development illustrates an important basic process in developmental biology known as "branching morphogenesis" shared by other organs such as the pancreas, kidney, and mammary glands. These organs all start out as small buds of epithelial cells surrounded by mesenchyme that undergo repeated rounds of outgrowth and branching. We have identified key signaling factors and pathways active in discrete populations of endoderm and mesoderm cells that direct the temporal and spatial pattern of branching.

    Second, we have used genetic lineage labeling techniques to identify a population of multipotent progenitor cells in the tips of the growing buds that give rise to all the specialized epithelial cell types of the adult lung. These cells have a high rate of proliferation and an undifferentiated morphology. We and others have identified a set of genes that are preferentially expressed in these cells (including Sox9 as shown in the figure below). We have made new conditional mutant strains of mice for testing the function of specific genes in promoting the proliferation and multipotency of the progenitor cells, and in directing the developmental fate of their descendants.

    Another goal of the lab is to identify cells in the adult lung that can mediate epithelial repair after damage by exogenous agents. Again, we have generated several new lines of mice for testing the behavior and repair potential of candidate adult lung stem/progenitor cells, including basal cells in the trachea, secretory (Clara) cells in the conducting airways, and type II cells in the alveoli. We have shown that ciliated cells do not proliferate after injury and are most likely a postmitotic population. By contrast, Clara cells proliferate extensively and give rise to ciliated cells. Whether Clara cells, or a specific subpopulation of them, can give rise to alveolar cell types in repair models is under investigation.

    Finally, we are interested in learning how the primordium of the lung is established in the embryonic foregut as a population of cells distinct from the future liver, pancreas and intestine. We also seek to understand how the single early foregut tube becomes separated into trachea and esophagus. Failure of the foregut to separate properly underlies a relatively common human birth defect known as tracheoesophageal fistula (TEF).

Section through E14.5 mouse lung showing
Sox9 in mulitpotent tip cells (red), differentiated
ciliated cells expressing Foxj1 (green) and
e-cadherin (blue) – Emma Rawlins

Recent Publications
Lu, Y, Thomson, J.M., Wang, H.Y.F., Hammond, S.M. and B.L.M. Hogan (2007) Transgenic overexpression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells Dev. Biology 310: 442-453. -PDF-

Que, J., Okubo, T., Goldenring, J., Nam K-T, Kimura, S., Morrisey, E.E, Taranova, O, Pevny, L and B.L.M. Hogan (2007) Multiple dose-dependent roles for Sox2 in the patterning and differentiation of the foregut Development 134: 2521-31. -PDF-

Okubo, T., Pevny, L. H. and B.L.M. Hogan (2006) Sox2 is required for development of taste bud sensory cells Genes and Development 20: 2654-2659. -PDF-

Rawlins, E., Ostrowski, L.E., Randell, S.H. and B.L.M. Hogan (2007) Lung development and repair: contribution of the ciliated cell lineage Proc Natl. Acad. Sci. USA 104: 410-417. -PDF-

Que, J., Choi, M., Ziel, J. and B.L.M. Hogan (2006) Morphogenesis of the trachea and esophagus: current players and new roles for noggin and Bmps. Differentiation (special issue on Branching Morphogenesis and Tubulogenesis) 74:422-437. -PDF-

Rawlins, E. and B.L.M. Hogan (2006) Epithelial stem cells of the lung: privileged few or opportunities for many? Development 133: 2455-2465. -PDF-

Eblaghie, M, Reedy, M., Oliver, T., Mishina, Y. and B.L.M. Hogan (2006) Evidence that autocrine signaling through Bmpr1a regulates the proliferation, survival and behavior of distal lung epithelial cells. Dev. Biology 291: 67-82 -PDF-

More information and some current projects

Additional publications since 1998  >>

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