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-: There are an estimated 39.5 million people
affected with asthma in the United States today.
And asthma is estimated to cost the US
roughly 76 to 80 billion dollars each year.
Now interestingly, only about five to 10 percent
of asthmatics actually count for over 50%
of the total asthmatic cost
and this group is known as the severe asthmatics.
They are characterized by being poorly responsive
to inhaled corticosteroids and bronchodilators.
My research focuses on the hypothesis
that horses affected with a severe asthma-like disease
called equine pasture asthma,
are able to serve as translational models
for finding novel therapeutic targets of asthma
specifically to decrease airway hyper-responsiveness,
which is one of the key features of asthma.
In work previously done by our lab,
we have found that horses affected with EPA
respond to airway spasmogens at diagnostic levels
that are used to diagnose severe adult asthmatics.
This is important because traditional animal models
of asthma, like mice and rats,
require much higher doses of those airway spasmogens
to reach those same levels,
making it really difficult to evaluate
any new drugs done on these models
that aim at reducing that airway hyper-responsiveness.
So to that end, we then took horses
that were affected with EPA and non-affected
and we took surgical lung samples,
as you see in the first picture here,
and we were able to dissect out those lung samples
and sequence MRNA looking for protein coding genes
that specifically increased
beta two adrenergic receptor signaling.
Now that's important because beta two
adrenergic receptor signaling is required
to actually develop the asthmatic phenotype.
We were able to find one gene that did just that
and it was of particular interest to us
because it has been shown to actually modulate
the cell membrane potential in the heart
and able to actually effect when your heart contracts.
So we then wanted to see where that gene
was expressed in our horses
and we saw that in horses affected with EPA,
versus not, that gene was actually expressed
in the airway smooth muscle
more than in controlled horses.
We then wanted to know what would happen
if we blocked that gene in bronchial rings
that were dissected from horses affected with EPA,
and we suspended those rings in a tissue-backed medium
that received increasing concentrations
of an airway spasmogen.
So we did just that and we saw that in the genes
that were actually received that blocker,
they constricted to a much lesser extent
than those that did not,
showing us that this gene is important
and looking at novel therapeutic targets for asthma
and also shows us the importance
of using animal models to study disease.
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