>> So for my PhD I chose
to take on a disease.
A disease that is the consequence
of a public health burden,
that has devastated our human
population for centuries.
That burden of course is smoking.
And the disease that I
study is called emphysema.
So within our lungs are millions
of tiny sacs called alveoli.
And these alveoli are
essential for bringing
in the oxygen that our
bodies need to stay alive.
So as you can imagine,
our bodies rely quite
heavily on the proper
and efficient function of these alveoli.
And alveolar integrity must be maintained
throughout our lifetime.
This is exactly the role
of lung macrophages.
These are special immune cells
that reside in our airway,
and normally function to
promote tissue health.
These are the cells that clean up the mess
after a major infection.
Or when the lungs are
damaged by toxic aerosols.
But for the twenty
percent of heavy smokers
who go on and develop emphysema,
lung macrophages appear to be taking
on a different function.
Instead of repairing the lung,
after years of exposure
to toxic tobacco smoke,
dysregulated macrophages are
just making the damage worse.
So while smoking may initiate disease,
it is dysregulated
macrophages that progress it.
This explains why emphysema
just continues to get worse,
even after you quit smoking.
And unfortunately,
there are currently no drugs
capable of curing emphysema,
or slowing its progression.
But our lab has worked hard to dissect
what exactly drives macrophage
dysregulation in emphysema.
First we identified a
pale of immune signals
that are found in the emphysematous lung,
but not in the healthy lung.
We then noticed that receptors
to which these signals bind
are found directly on the surface
of dysregulated macrophages.
So we think there's
interaction going on here.
We also noticed that mice deficient
in these signaling pathways
no longer get emphysema.
So for the remainder of this project,
I will show definitively
which signals are needed
for reprogramming lung macrophages
from tissue reparative
to tissue destructive.
I will determine the cellular sources
of these immune signals.
But most importantly I will determine
if we can block these
signals with therapeutics.
And finally take steps towards curing
what currently is the irreversible disease
that affects nearly 65
million people worldwide.
By the end of this project
I will have answered
the overarching question
in emphysema research.
Why do good macrophages go bad?
(audience applause)
