WEBVTT

NOTE duration: "00:04:08.448"


NOTE Confidence: 0.9734701

00:00:06.319 --> 00:00:07.060
The vasculature

NOTE Confidence: 0.97642684

00:00:08.080 --> 00:00:09.840
is the interface between the

NOTE Confidence: 0.97642684

00:00:09.840 --> 00:00:11.059
blood and the tissue,

NOTE Confidence: 0.99562836

00:00:11.440 --> 00:00:12.880
and it determines what you

NOTE Confidence: 0.99562836

00:00:12.880 --> 00:00:15.174
absorb from your blood and

NOTE Confidence: 0.99562836

00:00:15.174 --> 00:00:16.695
how waste products in the

NOTE Confidence: 0.99562836

00:00:16.695 --> 00:00:18.795
tissue get cleared and evacuated

NOTE Confidence: 0.99562836

00:00:19.095 --> 00:00:20.454
from the body. And so

NOTE Confidence: 0.99562836

00:00:20.454 --> 00:00:22.314
blood vessels function as gatekeepers

NOTE Confidence: 0.99562836

00:00:22.535 --> 00:00:23.195
of health.

NOTE Confidence: 0.98599035

00:00:23.654 --> 00:00:25.895
Vasculature growth is adapted to

NOTE Confidence: 0.98599035

00:00:25.895 --> 00:00:27.255
tissue growth. As long as

NOTE Confidence: 0.98599035

00:00:27.255 --> 00:00:29.660
tissue grows, vasculature will grow.

NOTE Confidence: 0.98599035

00:00:29.660 --> 00:00:31.359
And so many tissue diseases

NOTE Confidence: 0.99801636

00:00:31.740 --> 00:00:33.020
also have a root cause

NOTE Confidence: 0.99801636

00:00:33.020 --> 00:00:34.239
in defective vasculature.

NOTE Confidence: 0.9737438

00:00:39.500 --> 00:00:41.280
We're trying to better understand

NOTE Confidence: 0.9737438

00:00:41.340 --> 00:00:42.699
blood vessels with the goal

NOTE Confidence: 0.9737438

00:00:42.699 --> 00:00:44.495
of finding cures for the

NOTE Confidence: 0.9737438

00:00:44.495 --> 00:00:46.354
many diseases that are associated

NOTE Confidence: 0.9737438

00:00:46.495 --> 00:00:47.315
with defective

NOTE Confidence: 0.9649658

00:00:47.615 --> 00:00:48.115
vasculature.

NOTE Confidence: 0.9939033

00:00:48.575 --> 00:00:50.015
For vessels to form the

NOTE Confidence: 0.9939033

00:00:50.015 --> 00:00:51.854
right blood tissue interface, they

NOTE Confidence: 0.9939033

00:00:51.854 --> 00:00:52.895
have to be different in

NOTE Confidence: 0.9939033

00:00:52.895 --> 00:00:54.735
different tissues. For example, the

NOTE Confidence: 0.9939033

00:00:54.735 --> 00:00:56.655
kidney has very permeable blood

NOTE Confidence: 0.9939033

00:00:56.655 --> 00:00:58.510
vessels that allow exchange of

NOTE Confidence: 0.9939033

00:00:58.510 --> 00:01:00.110
waste products and and urine

NOTE Confidence: 0.9939033

00:01:00.110 --> 00:01:00.610
production.

NOTE Confidence: 0.9883996

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In the brain, blood vessels

NOTE Confidence: 0.9883996

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have to protect neurons. So

NOTE Confidence: 0.9883996

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in the brain, they form

NOTE Confidence: 0.9883996

00:01:04.990 --> 00:01:06.750
a very tight barrier and

NOTE Confidence: 0.9883996

00:01:06.750 --> 00:01:08.350
everything that gets across is

NOTE Confidence: 0.9883996

00:01:08.350 --> 00:01:10.030
very tightly regulated to keep

NOTE Confidence: 0.9883996

00:01:10.030 --> 00:01:10.930
the brain healthy.

NOTE Confidence: 0.96606445

00:01:11.275 --> 00:01:12.255
And one example,

NOTE Confidence: 0.98059475

00:01:12.634 --> 00:01:14.075
of our research is we

NOTE Confidence: 0.98059475

00:01:14.075 --> 00:01:15.694
found that there are molecules

NOTE Confidence: 0.98059475

00:01:15.755 --> 00:01:17.194
in the brain, a signaling

NOTE Confidence: 0.98059475

00:01:17.194 --> 00:01:19.034
pathway that is responsible for

NOTE Confidence: 0.98059475

00:01:19.034 --> 00:01:20.395
the integrity of the blood

NOTE Confidence: 0.98059475

00:01:20.395 --> 00:01:22.174
brain barrier. And we developed

NOTE Confidence: 0.98059475

00:01:22.235 --> 00:01:22.735
antibodies

NOTE Confidence: 0.9546712

00:01:23.320 --> 00:01:24.520
that can shut off this

NOTE Confidence: 0.9546712

00:01:24.520 --> 00:01:25.020
pathway,

NOTE Confidence: 0.9992327

00:01:25.320 --> 00:01:27.160
and these antibodies are able

NOTE Confidence: 0.9992327

00:01:27.160 --> 00:01:27.980
to transiently

NOTE Confidence: 0.95910645

00:01:28.360 --> 00:01:30.060
and safely and reversibly

NOTE Confidence: 0.97477216

00:01:30.440 --> 00:01:31.960
relax the blood brain barrier.

NOTE Confidence: 0.97477216

00:01:31.960 --> 00:01:33.080
And this allows you to

NOTE Confidence: 0.97477216

00:01:33.080 --> 00:01:34.680
get drugs into the diseased

NOTE Confidence: 0.97477216

00:01:34.680 --> 00:01:35.980
central nervous system.

NOTE Confidence: 0.98017436

00:01:36.975 --> 00:01:38.415
More than ninety nine percent

NOTE Confidence: 0.98017436

00:01:38.415 --> 00:01:39.935
of drugs cannot cross the

NOTE Confidence: 0.98017436

00:01:39.935 --> 00:01:41.455
blood brain barrier, and so

NOTE Confidence: 0.98017436

00:01:41.455 --> 00:01:43.215
brain diseases cannot be cured,

NOTE Confidence: 0.98017436

00:01:43.455 --> 00:01:44.495
currently. And so we are

NOTE Confidence: 0.98017436

00:01:44.495 --> 00:01:46.335
hoping that this, approach of

NOTE Confidence: 0.98017436

00:01:46.335 --> 00:01:47.795
blood brain barrier modulation

NOTE Confidence: 0.9992454

00:01:48.255 --> 00:01:49.615
will allow us to transform

NOTE Confidence: 0.9992454

00:01:49.615 --> 00:01:50.815
the way we treat brain

NOTE Confidence: 0.9992454

00:01:50.815 --> 00:01:51.315
diseases.

NOTE Confidence: 0.98072815

00:01:55.880 --> 00:01:57.320
Blood vessels, when you take

NOTE Confidence: 0.98072815

00:01:57.320 --> 00:01:58.360
them out of the body

NOTE Confidence: 0.98072815

00:01:58.360 --> 00:01:59.240
and you put them in

NOTE Confidence: 0.98072815

00:01:59.240 --> 00:02:00.759
a dish, they lose all

NOTE Confidence: 0.98072815

00:02:00.759 --> 00:02:02.920
these functional specialization. So for

NOTE Confidence: 0.98072815

00:02:02.920 --> 00:02:04.280
the longest time, we really

NOTE Confidence: 0.98072815

00:02:04.280 --> 00:02:06.345
couldn't study this organ specific

NOTE Confidence: 0.98072815

00:02:06.405 --> 00:02:07.865
difference in in the vasculature.

NOTE Confidence: 0.9536268

00:02:08.485 --> 00:02:10.325
Nowadays, we have single cell

NOTE Confidence: 0.9536268

00:02:10.325 --> 00:02:10.825
sequencing,

NOTE Confidence: 0.99461013

00:02:11.125 --> 00:02:12.165
and so we can take

NOTE Confidence: 0.99461013

00:02:12.165 --> 00:02:14.005
every single cell and determine

NOTE Confidence: 0.99461013

00:02:14.005 --> 00:02:15.305
its molecular composition.

NOTE Confidence: 0.9773702

00:02:16.005 --> 00:02:17.445
And this way, these hidden

NOTE Confidence: 0.9773702

00:02:17.445 --> 00:02:19.260
pathways that are responsible for

NOTE Confidence: 0.9773702

00:02:19.419 --> 00:02:21.439
organ specialization can be discovered.

NOTE Confidence: 0.9773702

00:02:21.500 --> 00:02:22.620
And so by reading the

NOTE Confidence: 0.9773702

00:02:22.620 --> 00:02:24.459
vasculature code, you can find

NOTE Confidence: 0.9773702

00:02:24.459 --> 00:02:25.980
molecules that are more expressed

NOTE Confidence: 0.9773702

00:02:25.980 --> 00:02:27.659
in one vascular bed compared

NOTE Confidence: 0.9773702

00:02:27.659 --> 00:02:29.419
to another. And usually, these

NOTE Confidence: 0.9773702

00:02:29.419 --> 00:02:30.939
molecules then also have a

NOTE Confidence: 0.9773702

00:02:30.939 --> 00:02:32.139
function there. So once these

NOTE Confidence: 0.9773702

00:02:32.139 --> 00:02:33.360
molecules are identified

NOTE Confidence: 0.986707

00:02:33.875 --> 00:02:35.315
by single cell sequencing, then

NOTE Confidence: 0.986707

00:02:35.315 --> 00:02:37.175
we can use biochemical techniques,

NOTE Confidence: 0.986707

00:02:37.315 --> 00:02:38.595
go back to cell culture,

NOTE Confidence: 0.986707

00:02:38.595 --> 00:02:40.035
and also test the function

NOTE Confidence: 0.986707

00:02:40.035 --> 00:02:41.555
of these molecules in genetic

NOTE Confidence: 0.986707

00:02:41.555 --> 00:02:43.334
approaches in model organisms.

NOTE Confidence: 0.9926758

00:02:44.194 --> 00:02:45.974
We also developed an MRI

NOTE Confidence: 0.9926758

00:02:46.035 --> 00:02:47.255
based imaging approach

NOTE Confidence: 0.977948

00:02:47.680 --> 00:02:48.900
to look at the meningeal

NOTE Confidence: 0.977948

00:02:48.960 --> 00:02:50.880
lymphatic vessels surrounding the brain

NOTE Confidence: 0.977948

00:02:50.880 --> 00:02:52.560
in human patients, and that

NOTE Confidence: 0.977948

00:02:52.560 --> 00:02:54.020
now allows us the possibility

NOTE Confidence: 0.99454755

00:02:54.480 --> 00:02:56.080
to investigate how patients with

NOTE Confidence: 0.99454755

00:02:56.080 --> 00:02:56.580
neurodegenerative

NOTE Confidence: 0.9898507

00:02:57.120 --> 00:02:59.440
diseases, how these diseases relate

NOTE Confidence: 0.9898507

00:02:59.440 --> 00:03:00.100
to dysfunctional,

NOTE Confidence: 0.9852702

00:03:00.800 --> 00:03:02.980
lymphatics and dysfunctional brain drainage,

NOTE Confidence: 0.9852702

00:03:03.275 --> 00:03:04.395
and then try to develop

NOTE Confidence: 0.9852702

00:03:04.395 --> 00:03:06.015
approaches to make these lymphatic

NOTE Confidence: 0.9852702

00:03:06.235 --> 00:03:07.995
vessels better to improve brain

NOTE Confidence: 0.9852702

00:03:07.995 --> 00:03:08.495
health.

NOTE Confidence: 0.9137207

00:03:14.075 --> 00:03:15.855
I believe it's very important

NOTE Confidence: 0.9166667

00:03:16.580 --> 00:03:17.959
to understand diseases,

NOTE Confidence: 0.96970624

00:03:18.500 --> 00:03:20.419
that you understand how the

NOTE Confidence: 0.96970624

00:03:20.419 --> 00:03:21.799
normal healthy vasculature

NOTE Confidence: 0.9450141

00:03:22.099 --> 00:03:23.860
develops. And then understanding what

NOTE Confidence: 0.9450141

00:03:23.860 --> 00:03:25.079
is different in diseases,

NOTE Confidence: 0.98391724

00:03:25.459 --> 00:03:26.980
you can find pathways that

NOTE Confidence: 0.98391724

00:03:26.980 --> 00:03:28.739
are responsible for diseases and

NOTE Confidence: 0.98391724

00:03:28.739 --> 00:03:30.659
then develop drugs to tackle

NOTE Confidence: 0.98391724

00:03:30.659 --> 00:03:31.095
this.

NOTE Confidence: 0.99365234

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It's estimated

NOTE Confidence: 0.9969308

00:03:32.695 --> 00:03:34.455
that two thirds of all

NOTE Confidence: 0.9969308

00:03:34.455 --> 00:03:35.515
human mortality

NOTE Confidence: 0.986084

00:03:36.215 --> 00:03:38.475
is directly related to vascular

NOTE Confidence: 0.986084

00:03:38.615 --> 00:03:39.115
dysfunction.

NOTE Confidence: 0.9600423

00:03:39.575 --> 00:03:40.775
And so our goal as

NOTE Confidence: 0.9600423

00:03:40.775 --> 00:03:41.275
researchers

NOTE Confidence: 0.98249424

00:03:41.575 --> 00:03:43.095
is to explore these sixty

NOTE Confidence: 0.98249424

00:03:43.095 --> 00:03:44.315
thousand miles of endothelium

NOTE Confidence: 0.9802912

00:03:44.615 --> 00:03:46.470
and find new approaches to

NOTE Confidence: 0.9802912

00:03:46.470 --> 00:03:47.990
keep your tissues healthier for

NOTE Confidence: 0.9802912

00:03:47.990 --> 00:03:49.830
a longer time. No single

NOTE Confidence: 0.9802912

00:03:49.830 --> 00:03:51.430
laboratory can tackle this on

NOTE Confidence: 0.9802912

00:03:51.430 --> 00:03:52.390
its own, but in a

NOTE Confidence: 0.9802912

00:03:52.390 --> 00:03:53.990
place like Yale, by working

NOTE Confidence: 0.9802912

00:03:53.990 --> 00:03:55.850
together, exchanging ideas,

NOTE Confidence: 0.98489815

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tools, and methods to test

NOTE Confidence: 0.98489815

00:03:57.830 --> 00:03:58.570
these ideas,

NOTE Confidence: 0.9858023

00:03:58.883 --> 00:04:00.482
we can make inroads and

NOTE Confidence: 0.9858023

00:04:00.482 --> 00:04:02.163
come together for the betterment

NOTE Confidence: 0.9858023

00:04:02.163 --> 00:04:03.142
of human health.