Vascular Patterning, Signaling Pathways, & Antibodies - The Eichmann Lab at Yale School of Medicine

Transcript

• 00:06The vasculature
• 00:08is the interface between the
• 00:10blood and the tissue,
• 00:11and it determines what you
• 00:13absorb from your blood and
• 00:15how waste products in the
• 00:17tissue get cleared and evacuated
• 00:19from the body. And so
• 00:20blood vessels function as gatekeepers
• 00:23of health.
• 00:24Vasculature growth is adapted to
• 00:26tissue growth. As long as
• 00:27tissue grows, vasculature will grow.
• 00:30And so many tissue diseases
• 00:32also have a root cause
• 00:33in defective vasculature.
• 00:40We're trying to better understand
• 00:41blood vessels with the goal
• 00:43of finding cures for the
• 00:44many diseases that are associated
• 00:46with defective
• 00:48vasculature.
• 00:49For vessels to form the
• 00:50right blood tissue interface, they
• 00:52have to be different in
• 00:53different tissues. For example, the
• 00:55kidney has very permeable blood
• 00:57vessels that allow exchange of
• 00:59waste products and and urine
• 01:00production.
• 01:01In the brain, blood vessels
• 01:02have to protect neurons. So
• 01:04in the brain, they form
• 01:05a very tight barrier and
• 01:07everything that gets across is
• 01:08very tightly regulated to keep
• 01:10the brain healthy.
• 01:11And one example,
• 01:13of our research is we
• 01:14found that there are molecules
• 01:16in the brain, a signaling
• 01:17pathway that is responsible for
• 01:19the integrity of the blood
• 01:20brain barrier. And we developed
• 01:22antibodies
• 01:23that can shut off this
• 01:25pathway,
• 01:25and these antibodies are able
• 01:27to transiently
• 01:28and safely and reversibly
• 01:30relax the blood brain barrier.
• 01:32And this allows you to
• 01:33get drugs into the diseased
• 01:35central nervous system.
• 01:37More than ninety nine percent
• 01:38of drugs cannot cross the
• 01:40blood brain barrier, and so
• 01:41brain diseases cannot be cured,
• 01:43currently. And so we are
• 01:44hoping that this, approach of
• 01:46blood brain barrier modulation
• 01:48will allow us to transform
• 01:50the way we treat brain
• 01:51diseases.
• 01:56Blood vessels, when you take
• 01:57them out of the body
• 01:58and you put them in
• 01:59a dish, they lose all
• 02:01these functional specialization. So for
• 02:03the longest time, we really
• 02:04couldn't study this organ specific
• 02:06difference in in the vasculature.
• 02:08Nowadays, we have single cell
• 02:10sequencing,
• 02:11and so we can take
• 02:12every single cell and determine
• 02:14its molecular composition.
• 02:16And this way, these hidden
• 02:17pathways that are responsible for
• 02:19organ specialization can be discovered.
• 02:22And so by reading the
• 02:23vasculature code, you can find
• 02:24molecules that are more expressed
• 02:26in one vascular bed compared
• 02:28to another. And usually, these
• 02:29molecules then also have a
• 02:31function there. So once these
• 02:32molecules are identified
• 02:34by single cell sequencing, then
• 02:35we can use biochemical techniques,
• 02:37go back to cell culture,
• 02:39and also test the function
• 02:40of these molecules in genetic
• 02:42approaches in model organisms.
• 02:44We also developed an MRI
• 02:46based imaging approach
• 02:48to look at the meningeal
• 02:49lymphatic vessels surrounding the brain
• 02:51in human patients, and that
• 02:53now allows us the possibility
• 02:54to investigate how patients with
• 02:56neurodegenerative
• 02:57diseases, how these diseases relate
• 02:59to dysfunctional,
• 03:01lymphatics and dysfunctional brain drainage,
• 03:03and then try to develop
• 03:04approaches to make these lymphatic
• 03:06vessels better to improve brain
• 03:08health.
• 03:14I believe it's very important
• 03:17to understand diseases,
• 03:19that you understand how the
• 03:20normal healthy vasculature
• 03:22develops. And then understanding what
• 03:24is different in diseases,
• 03:25you can find pathways that
• 03:27are responsible for diseases and
• 03:29then develop drugs to tackle
• 03:31this.
• 03:32It's estimated
• 03:33that two thirds of all
• 03:34human mortality
• 03:36is directly related to vascular
• 03:39dysfunction.
• 03:40And so our goal as
• 03:41researchers
• 03:42is to explore these sixty
• 03:43thousand miles of endothelium
• 03:45and find new approaches to
• 03:46keep your tissues healthier for
• 03:48a longer time. No single
• 03:50laboratory can tackle this on
• 03:51its own, but in a
• 03:52place like Yale, by working
• 03:54together, exchanging ideas,
• 03:56tools, and methods to test
• 03:58these ideas,
• 03:59we can make inroads and
• 04:00come together for the betterment
• 04:02of human health.