Research in the Hogan lab is focused
on two areas: (1) embryonic stem cells
and primordial germ cell biology and
(2) organogenesis: the process by which
a complex and highly specialized organ
- in our case, the lung - develops
from a small population of undifferentiated
embryonic cells. We are driven by both
curiosity and practical considerations
- if we understand how cellular interactions
and signaling pathways control the
differentiation of stem cells and the
development of organs like the lung
we may be able to enhance tissue regeneration
and repair, and even grow endodermal
organs in the laboratory.
We are interested in the lung for
a variety of reasons. First, it is
an elegant experimental system for
studying basic mechanisms underlying
the development of all branched organ
systems, including the pancreas and
mammary glands. These organs all start
out as small buds of epithelial cells
surrounded by mesenchyme that undergo
repeated rounds of budding and branching,
a process known as "branching
morphogenesis". Secondly, although
the lung is absolutely essential for
human life, relatively little is know
about how its development is controlled
and how this could be accelerated in
premature babies born with immature
lungs. Also, surprisingly little is
known about the response of lung cells
to injury by environmental toxins and
irradiation, or the remodeling of lung
structure in disorders such as asthma.
This remodeling can involve dramatic
switches in the phenotype of bronchial
cells, for example from being mostly
ciliated to mostly mucous producing.
Does this involve changes in cells
derived from stem cells in the adult
lung, or the proliferation and preprogramming
of already differentiated cells? Finally,
we are interested in learning how the
epithelial primordium of the lung is
established in the embryonic foregut
as a population of cells distinct from
the primordia of other endodermal organs
such as the liver, pancreas and intestine.
Our interest is practical - we would
like to know how to generate different
kinds of endodermal cells from undifferentiated
embryonic stem (ES) cells, and, more
speculatively, whether it is possible
to switch progenitor/stem cells derived
from the adult lung or trachea into
equivalent cells of other endodermal
organs such as the pancreas. Such switching
between endodermal phenotypes occurs
in pathological conditions known as
metaplasia - we want to know if it
is possible to control this process
experimentally, with obvious practical
applications.
The Hogan lab has a long standing
interest in the biology of mammalian
primordial germ cells - how they are
generated, how they reach the gonad
and interact with somatic cells, and
how they are reprogrammed to give rise
to pluripotent embryonic germ (EG)
cells. The projects underway overlap
conceptually and pratically with the
lung projects. In both cases we use
a variety of technical approaches,
including culture of embryonic cells,
confocal and time lapse microscopy,
genetic manipulation of the mouse,
tissue grafting and, more recently,
gene knockdown with lentivirus vectors.
