WEBVTT

NOTE duration: "00:04:11.477"


NOTE Confidence: 0.98699176

00:00:05.040 --> 00:00:06.580
Cell death is a key

NOTE Confidence: 0.98699176

00:00:06.640 --> 00:00:08.639
process that's necessary even in

NOTE Confidence: 0.98699176

00:00:08.639 --> 00:00:10.000
development in order to get

NOTE Confidence: 0.98699176

00:00:10.000 --> 00:00:11.300
a viable organism.

NOTE Confidence: 0.96776295

00:00:13.039 --> 00:00:14.719
This program is called upon

NOTE Confidence: 0.96776295

00:00:14.719 --> 00:00:15.975
again over and over in

NOTE Confidence: 0.96776295

00:00:16.055 --> 00:00:17.655
in almost every disease I

NOTE Confidence: 0.96776295

00:00:17.655 --> 00:00:19.335
can think of, where you

NOTE Confidence: 0.96776295

00:00:19.335 --> 00:00:21.255
either have diseases where there's

NOTE Confidence: 0.96776295

00:00:21.255 --> 00:00:23.015
too little cell death, such

NOTE Confidence: 0.96776295

00:00:23.015 --> 00:00:23.915
as in cancer,

NOTE Confidence: 0.98782504

00:00:25.175 --> 00:00:26.454
or you have diseases where

NOTE Confidence: 0.98782504

00:00:26.454 --> 00:00:27.895
there's too much cell death,

NOTE Confidence: 0.98782504

00:00:27.895 --> 00:00:29.494
such as in strokes or

NOTE Confidence: 0.98782504

00:00:29.494 --> 00:00:30.315
heart attacks.

NOTE Confidence: 0.95352143

00:00:35.360 --> 00:00:36.720
My lab is very interested

NOTE Confidence: 0.95352143

00:00:36.720 --> 00:00:38.080
in the process of cell

NOTE Confidence: 0.95352143

00:00:38.080 --> 00:00:39.860
death. That is how cells

NOTE Confidence: 0.95352143

00:00:40.159 --> 00:00:41.600
no longer survive. What are

NOTE Confidence: 0.95352143

00:00:41.600 --> 00:00:43.280
the things that cause them

NOTE Confidence: 0.95352143

00:00:43.280 --> 00:00:44.159
to die and then what

NOTE Confidence: 0.95352143

00:00:44.159 --> 00:00:46.159
are the molecular pathways by

NOTE Confidence: 0.95352143

00:00:46.159 --> 00:00:47.055
which they can die?

NOTE Confidence: 0.9960895

00:00:48.575 --> 00:00:49.695
So if we can determine

NOTE Confidence: 0.9960895

00:00:49.695 --> 00:00:51.055
the pathway by which those

NOTE Confidence: 0.9960895

00:00:51.055 --> 00:00:52.575
cells are being forced to

NOTE Confidence: 0.9960895

00:00:52.575 --> 00:00:54.655
die, we can then prevent

NOTE Confidence: 0.9960895

00:00:54.655 --> 00:00:56.255
that death and maintain the

NOTE Confidence: 0.9960895

00:00:56.255 --> 00:00:57.715
function of those cells.

NOTE Confidence: 0.9761925

00:01:01.380 --> 00:01:02.579
There are multiple different types

NOTE Confidence: 0.9761925

00:01:02.579 --> 00:01:03.860
of death pathways that one

NOTE Confidence: 0.9761925

00:01:03.860 --> 00:01:04.360
could,

NOTE Confidence: 0.9801003

00:01:04.819 --> 00:01:06.180
attack. We look at two

NOTE Confidence: 0.9801003

00:01:06.180 --> 00:01:08.100
in particular. One is the

NOTE Confidence: 0.9801003

00:01:08.100 --> 00:01:10.120
intrinsic pathway of apoptosis,

NOTE Confidence: 0.9756157

00:01:10.819 --> 00:01:12.340
which is mediated by a

NOTE Confidence: 0.9756157

00:01:12.340 --> 00:01:14.120
family of genes called BCL2

NOTE Confidence: 0.8789091

00:01:14.500 --> 00:01:15.479
family members,

NOTE Confidence: 0.91460156

00:01:15.780 --> 00:01:17.194
one of which we study

NOTE Confidence: 0.91460156

00:01:17.194 --> 00:01:18.955
that's really poorly understood is

NOTE Confidence: 0.91460156

00:01:18.955 --> 00:01:20.635
called BOC or b o

NOTE Confidence: 0.91460156

00:01:20.635 --> 00:01:21.135
k.

NOTE Confidence: 0.85332114

00:01:21.915 --> 00:01:22.415
BOC,

NOTE Confidence: 0.96519053

00:01:22.875 --> 00:01:24.235
unlike all the other BCL

NOTE Confidence: 0.96519053

00:01:24.235 --> 00:01:25.595
two family members which primarily

NOTE Confidence: 0.96519053

00:01:25.595 --> 00:01:27.035
act at the mitochondria, acts

NOTE Confidence: 0.96519053

00:01:27.035 --> 00:01:28.955
at the endoplasmic reticulum or

NOTE Confidence: 0.96519053

00:01:28.955 --> 00:01:29.775
the ER.

NOTE Confidence: 0.966527

00:01:30.569 --> 00:01:32.569
BAC is important for ER

NOTE Confidence: 0.966527

00:01:32.569 --> 00:01:33.069
stress,

NOTE Confidence: 0.95365494

00:01:33.929 --> 00:01:35.289
agents, and there are many

NOTE Confidence: 0.95365494

00:01:35.289 --> 00:01:37.469
different diseases which involve

NOTE Confidence: 0.85917324

00:01:37.850 --> 00:01:39.770
ER stress and or invoke

NOTE Confidence: 0.85917324

00:01:39.770 --> 00:01:40.750
it. And,

NOTE Confidence: 0.98610216

00:01:41.289 --> 00:01:41.789
tauopathies

NOTE Confidence: 0.9760259

00:01:42.329 --> 00:01:44.189
are one in particular because

NOTE Confidence: 0.9760259

00:01:44.250 --> 00:01:45.785
in this form of neurodegeneration,

NOTE Confidence: 0.9733506

00:01:46.725 --> 00:01:48.805
there's an overproduction of this

NOTE Confidence: 0.9733506

00:01:48.805 --> 00:01:51.545
protein tau, which then forms

NOTE Confidence: 0.9733506

00:01:51.765 --> 00:01:52.265
oligomers

NOTE Confidence: 0.96832615

00:01:52.885 --> 00:01:54.325
and causes a lot of

NOTE Confidence: 0.96832615

00:01:54.325 --> 00:01:55.145
ER stress.

NOTE Confidence: 0.9947751

00:01:55.605 --> 00:01:56.985
And as the name neurodegeneration

NOTE Confidence: 0.9974272

00:01:57.445 --> 00:01:57.945
implies,

NOTE Confidence: 0.99204504

00:01:58.300 --> 00:01:59.740
the main feature we see

NOTE Confidence: 0.99204504

00:01:59.740 --> 00:02:01.580
is loss of neurons, so

NOTE Confidence: 0.99204504

00:02:01.580 --> 00:02:02.080
death.

NOTE Confidence: 0.9968175

00:02:03.020 --> 00:02:04.860
If we learn exactly how

NOTE Confidence: 0.9968175

00:02:04.860 --> 00:02:06.380
Bach is mediating cell death

NOTE Confidence: 0.9968175

00:02:06.380 --> 00:02:07.600
within these neurons,

NOTE Confidence: 0.988863

00:02:07.900 --> 00:02:09.260
then perhaps we can find

NOTE Confidence: 0.988863

00:02:09.260 --> 00:02:10.319
a way to inhibit

NOTE Confidence: 0.9974061

00:02:10.860 --> 00:02:12.780
Bach's action and keep these

NOTE Confidence: 0.9974061

00:02:12.780 --> 00:02:13.760
neurons alive.

NOTE Confidence: 0.98397464

00:02:16.435 --> 00:02:18.435
The second way is the

NOTE Confidence: 0.98397464

00:02:18.435 --> 00:02:20.595
extrinsic pathway of cell death.

NOTE Confidence: 0.98397464

00:02:20.595 --> 00:02:23.075
That's where other cells are

NOTE Confidence: 0.98397464

00:02:23.075 --> 00:02:24.835
from the outside causing the

NOTE Confidence: 0.98397464

00:02:24.835 --> 00:02:26.294
death of the cells.

NOTE Confidence: 0.9392378

00:02:26.860 --> 00:02:28.300
So often in the immune

NOTE Confidence: 0.9392378

00:02:28.300 --> 00:02:29.820
system, T cells are known

NOTE Confidence: 0.9392378

00:02:29.820 --> 00:02:31.260
as killers. They kill other

NOTE Confidence: 0.9392378

00:02:31.260 --> 00:02:32.960
cells, and so they extrinsically

NOTE Confidence: 0.9917061

00:02:33.260 --> 00:02:34.460
cause the death of those

NOTE Confidence: 0.9917061

00:02:34.460 --> 00:02:35.280
other cells.

NOTE Confidence: 0.97253704

00:02:35.820 --> 00:02:37.820
And it was learned that

NOTE Confidence: 0.97253704

00:02:37.820 --> 00:02:39.820
in addition to infected cells,

NOTE Confidence: 0.97253704

00:02:39.820 --> 00:02:41.055
T cells are also killing

NOTE Confidence: 0.97253704

00:02:41.215 --> 00:02:42.275
cancer cells recognizing

NOTE Confidence: 0.99932605

00:02:42.734 --> 00:02:43.715
cancer antigens

NOTE Confidence: 0.97126746

00:02:44.014 --> 00:02:45.075
that are expressed.

NOTE Confidence: 0.99750143

00:02:45.694 --> 00:02:46.194
But

NOTE Confidence: 0.9749638

00:02:46.495 --> 00:02:48.014
not every cancer has a

NOTE Confidence: 0.9749638

00:02:48.014 --> 00:02:49.375
good antigen and a t

NOTE Confidence: 0.9749638

00:02:49.375 --> 00:02:51.215
cell receptor that recognizes it

NOTE Confidence: 0.9749638

00:02:51.215 --> 00:02:52.174
in order to kill it.

NOTE Confidence: 0.9749638

00:02:52.174 --> 00:02:53.474
And so people have made

NOTE Confidence: 0.9749638

00:02:53.534 --> 00:02:55.294
what they call chimeric antigen

NOTE Confidence: 0.9749638

00:02:55.294 --> 00:02:55.794
receptors

NOTE Confidence: 0.9450393

00:02:56.174 --> 00:02:58.110
or CAR T cells, and

NOTE Confidence: 0.9450393

00:02:58.110 --> 00:03:00.510
the most successful example already

NOTE Confidence: 0.9450393

00:03:00.510 --> 00:03:02.430
approved is going after B

NOTE Confidence: 0.9450393

00:03:02.430 --> 00:03:04.210
cell leukemias and lymphomas

NOTE Confidence: 0.9129054

00:03:04.590 --> 00:03:06.350
against a molecule called CD

NOTE Confidence: 0.9129054

00:03:06.350 --> 00:03:06.850
nineteen.

NOTE Confidence: 0.9942904

00:03:08.270 --> 00:03:09.790
What we've been very interested

NOTE Confidence: 0.9942904

00:03:09.790 --> 00:03:11.565
in recently is expanding this

NOTE Confidence: 0.9942904

00:03:11.965 --> 00:03:13.185
to beyond

NOTE Confidence: 0.9790559

00:03:13.485 --> 00:03:15.805
these blood cancers to solid

NOTE Confidence: 0.9790559

00:03:15.805 --> 00:03:17.245
tumors. And so we've been

NOTE Confidence: 0.9790559

00:03:17.245 --> 00:03:19.085
going after other targets that

NOTE Confidence: 0.9790559

00:03:19.085 --> 00:03:19.825
are expressed

NOTE Confidence: 0.9900037

00:03:20.125 --> 00:03:21.885
highly on solid tumors and

NOTE Confidence: 0.9900037

00:03:21.885 --> 00:03:23.505
trying to boost the activity

NOTE Confidence: 0.9843361

00:03:23.885 --> 00:03:25.270
of these CAR T cells

NOTE Confidence: 0.9843361

00:03:25.270 --> 00:03:26.250
to kill them.

NOTE Confidence: 0.9746464

00:03:32.709 --> 00:03:34.230
The overall goal of the

NOTE Confidence: 0.9746464

00:03:34.230 --> 00:03:36.490
lab really is the selective

NOTE Confidence: 0.9592415

00:03:36.950 --> 00:03:38.805
therapeutic control of cell death.

NOTE Confidence: 0.99481106

00:03:39.765 --> 00:03:41.224
I'm a physician scientist.

NOTE Confidence: 0.9915751

00:03:41.844 --> 00:03:43.444
I spend eighty percent of

NOTE Confidence: 0.9915751

00:03:43.444 --> 00:03:45.204
my time running this research

NOTE Confidence: 0.9915751

00:03:45.204 --> 00:03:46.805
laboratory. The other twenty percent

NOTE Confidence: 0.9915751

00:03:46.805 --> 00:03:48.004
of my time, I'm a

NOTE Confidence: 0.9915751

00:03:48.004 --> 00:03:48.504
hematopathologist

NOTE Confidence: 0.79614544

00:03:49.284 --> 00:03:50.344
where I'm diagnosing,

NOTE Confidence: 0.9994783

00:03:51.204 --> 00:03:51.704
lymphomas,

NOTE Confidence: 0.95596087

00:03:52.084 --> 00:03:52.584
leukemias,

NOTE Confidence: 0.99949837

00:03:53.090 --> 00:03:53.910
and myelomas

NOTE Confidence: 0.95736635

00:03:54.210 --> 00:03:55.110
within patients.

NOTE Confidence: 0.98792255

00:03:55.410 --> 00:03:57.490
And so I'm very familiar

NOTE Confidence: 0.98792255

00:03:57.490 --> 00:03:59.170
with the blood system and

NOTE Confidence: 0.98792255

00:03:59.170 --> 00:04:00.290
how it can produce cancers,

NOTE Confidence: 0.98792255

00:04:00.290 --> 00:04:01.250
but I'm also very familiar

NOTE Confidence: 0.98792255

00:04:01.250 --> 00:04:02.050
with the blood system and

NOTE Confidence: 0.98792255

00:04:02.050 --> 00:04:03.270
how it can be harnessed

NOTE Confidence: 0.98792255

00:04:03.410 --> 00:04:04.450
in order to,

NOTE Confidence: 0.79095125

00:04:04.770 --> 00:04:05.270
affect,

NOTE Confidence: 0.98815084

00:04:05.730 --> 00:04:06.230
cure.