WEBVTT

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Inborn errors of immunity is
an umbrella term we think about

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for these primarily pediatric immune disorders

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and the way I like to think about it is
these are genetic diseases.

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If you think about all humans on Earth

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as being sort of part of a bell curve, right,

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in terms of your immune responsiveness.

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We like to study the extremes.

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So the kids who have really low immune function

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and therefore get a lot of infections,

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and also the kids on the other
side of the bell curve

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who have a really high immune response

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and rather than infection,

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they suffer from immune-mediated
damage to their tissues.

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So my lab is really excited
to learn fundamental immunology

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and really how the immune
system works as a system,

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starting first with patients

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and these are primarily pediatric patients
who have severe immune diseases.

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But we test the hypothesis these kids
could be sick from a single gene mutation

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and then we used models to dissect mechanisms
and come up with precision therapies.

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We do genomics.

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So this is where we sequenced the whole genome

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to find that sort of needle in the haystack.

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So if we're right
that the hypothesis is true

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that this kid is sick from
a single gene mutation,

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we can identify that using genomics.

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And then we also use models.

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So we'll use Crispr to engineer
versions of the human mutation

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and then can do all kinds of immunology assays.

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So it allows us to do in vitro work.

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In addition, we do experiments to understand why

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this gene mutation could make their immune
cells function abnormally

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and then we also test therapies
and things in models

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that our goal then is to
translate back into the patients

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and, importantly, it's not just
the patients with the rare disease.

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Also, we think that by studying
these extremes on the sort of bell curve,

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we're learning fundamental immunobiology
that applies to more common diseases

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as well, but maybe in less severe form.

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Precision therapy,

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understanding the gene mutation,

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makes you realize what kind of
treatment is best for them.

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So this is where it leads.

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It leads to precision therapy
for rare disease.

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But in addition, because we're learning
fundamental immunology

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directly from patients,
it builds foundational knowledge

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that allows us to spin off
new knowledge in ways one can't predict.

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So it can lead to, we think,
more well-defined foundations

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about how the human immune system works
and how we might manipulate it.

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It's an amazing time to be in
medicine and in science,

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where we've got so many different
potential therapies on the shelves, right?

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And there are ways we can modulate the immune system in ways that have really, really advanced

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and it's partly matchmaking,
trying to understand

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why is this person sick
so we can choose the right therapy

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and also innovating around new therapies
because as our knowledge expands,

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we can think about how we could
rewire these these circuits.