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.
See a picture of Dr. Hogan's research
in our Gallery.
