I'd like to share with you
something that excites me when I
wake up each morning, something
that I'm very passionate about.
Imagine that you are a 20
to 30 year old individual.
You're perfectly healthy, and
it's the prime
time of your life.
But, one day, you notice that
the skin on your fingertips and
your toes are no longer soft,
but they're stiff as plastic.
And the stiffening of your skin
begins to spread up your arms,
your face, your torso.
And within a few years,
it spreads into your heart and
your lungs so that even
breathing becomes the most
difficult thing you can
do at your young age.
This is the reality of our
patients with scleroderma.
Scleroderma is
an aggressive disease that
predominantly affects
young women.
And we have no cure,
because, well,
we just don't
understand the disease.
You see, for many other
conditions, we've been able to
identify specific genetic cause,
a specific change in the DNA.
But despite numerous
genetic screens using
the best technology,
we still don't know the genetic
cause of scleroderma.
Their DNA sequences
essentially appear normal.
So what's causing scleroderma,
and how can we fix it?
To address these questions,
I took skin biopsies from
healthy individuals, or
patients with scleroderma
here at Johns Hopkins.
And I found that the scleroderma
cells produce a ton
of proteins that cause
skin stiffening.
But that's perplexing, isn't it?
Why are scleroderma cells
behaving so abnormally that
their DNA sequences
are essentially normal?
What are we missing here?
What we often neglect is
that the DNA is not simply
a linear string of sequences.
Rather, it's wound up
to create a complex,
three-dimensional structure
as illustrated above.
As studies show, the changes
in the shape of the DNA has
a profound effect on the cells.
And so we went back and
we performed a new type of DNA
sequencing called APC sequences,
and we found that the actual
shape of the DNA in scleroderma
cells were profoundly different.
And we demonstrated that
the altered shape is actually
allowing uncontrolled production
of these proteins that cause
skin tightening.
So it's a very exciting time for
us.
it's an exciting time, because
we finely found a foothold to
understanding scleroderma.
It's an exciting time because
of advanced new treatment
modalities that can actually
normalize the shape of the DNA
and the behavior of these cells.
But it's an exciting time,
because it advances
a new perspective in
understanding human pathology.
What other enigmatic
diseases can we now explain,
knowing that the DNA shape
can wreak havoc in the cell?
This is what I'm
passionate about.
Thank you.
>> [APPLAUSE]
