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

    The Hogan lab studies the cellular and genetic mechanisms underlying the development, maintenance and repair of organs derived from embryonic foregut endoderm. We focus on the lung, using the mouse as a model organism. We are particularly interested in the stem cells that play an essential role in the development of the lung and its repair after injury. We are driven by both curiosity and by practical considerations. We believe that in the long run knowledge about the cells, signaling pathways and genetic programs required for the growth, development and regeneration of the lung will translate into new approaches to clinical problems. These include promoting lung maturation in premature babies and repair of lung epithelium after damage by harmful agents, inhibiting pulmonary fibrosis, and blocking the growth of tumors.

    We focus on the lung for several reasons. First, its development depends on a fundamental developmental process known as "branching morphogenesis" shared by other organs such as the kidney and mammary glands. These organs initiate as small buds of epithelial and mesenchymal cells that undergo repeated rounds of outgrowth and branching. We have contributed to knowledge about branching morphogenesis by identifying signaling factors and pathways active in discrete populations of cells that direct the temporal and spatial pattern of airway branching. Second, pulmonary disorders affect millions of people world wide and many disorders such as lung cancer, COPD and fibrosis remain essentially intractable to therapy. While exciting progress has been made in understanding how tissue stem cells contribute to the growth and repair of other adult organ systems, still relatively little is known about their contributions in the lung. Our goal is to address this deficiency.

    One hallmark of our work is the generation of mouse lines in which genes can be conditionally manipulated in specific cells in the lung. This allows us to test the function of genes and to trace the fate of cells in the intact organ. We have used lineage tracing to identify a population of multipotent progenitor cells in the tips of the rapidly growing lung buds that give rise to all the specialized epithelial cell types of the adult organ. We and others have identified a set of genes preferentially expressed in these cells (including Sox9 shown in the figure below). We have also generated several new lines of mice to test the role of candidate stem cells resident in the adult lung, including Trp63+ Krt5+ basal cells in the trachea and larger airways, secretory (Clara) cells in the conducting airways, and Type II cells in the alveoli.

    We are particularly interested in the basal stem cells of the mouse trachea because they provide an important model for basal cells in the small airways of the human lung that often become damaged or occluded in disease. We have developed methods for isolating basal cells, growing them in culture and manipulating genes in them, all techniques being exploited to test specific hypotheses about their role in airway maintenance, barrier function, remodeling and repair. Most recently, we have used lineage tracing to show that mature Type II cells do not undergo epithelial-to-mesenchymal transition during experimental fibrosis. Rather, we find that multiple mesenchymal cell types, including pericytes, likely contribute to the fibrotic lesions. Our overall hypothesis is that failure of the alveolar epithelial cells to proliferate and differentiate after damage can promote the development and persistence of fibrosis. We are testing this idea using a variety of genetic approaches.

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
Rock, J.R. and B.L.M. Hogan (2011) Epithelial progenitor cells in lung development, maintenance, repair and disease Annu. Rev. Cell Dev. Biol. 27: 4.1 - 4.20 -PDF-

Rock, J.R., Gao, X., Xue, Y., Randell S.R., Kong Y-Y and B.L.M. Hogan (2011) Notch-dependent differentiation of adult airway basal stem cells Cell Stem Cell 8: 639-648 Cited in Faculty of 1000 -PDF-

Jovov, B., Que, J., Tobey, N.A., Djukic, Z., Hogan, B.L.M. and R.C. Orlando (2011) Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease American Journal of Gastroenterology On line -PDF-

Rodriguez, P., Da Silva, S., Oxburgh, L., Wang, F. Hogan, B.L.M. and J. Que (2010) BMP signaling in the development of the mouse esophagus and forestomach Development 137: 4171-4176. -PDF-

Rock, J., Randell, S.H. and B.L.M. Hogan (2010) Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling Disease Models and Mechanisms 3: 545 – 556. -PDF-

Morrisey, E. and B.L.M. Hogan (2010) Preparing for the First Breath: Genetic and Cellular mechanisms in Lung Development Dev. Cell 18: 8-23 -PDF-

Lu, Y., Futtner, C., Rock, J., Xu, X., Whitworth, W., Hogan, B.L.M. and M. Onaitis (2010) Evidence that SOX2 overexpression is oncogenic in the lung. PLoS One 5:e11022. -PDF-

Rawlins et al (2009) The Id2+ distal tip  lung epithelium contains individual multipotent embryonic progenitor cells. Development 136: 3741-3745. -PDF-

Rock, J., Onaitis, M.W., Rawlins, E.L., Lu, Y., Clark, C.P., Xue, Y., Randell, S.H., and B.L.M. Hogan (2009) Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl. Acad. Sci. USA 106: 12771-12775. -PDF-

Rawlins, E.L., Okubo, T., Xue, Y., Brass, D.M., Auten, R.L., Hasegawa, H., Wang, F. and B.L.M. Hogan (2009) The role of Scb1a1+ Clara cells in the long term maintenance and repair of lung airway but not alveolar epithelium. Cell Stem Cell 4: 525-534. -PDF-

Current Projects

Lab Members

Additional publications since 1998  >>

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