WEBVTT NOTE duration: "00:03:31.968" NOTE Confidence: 0.98466295 00:00:05.359 --> 00:00:06.899 The skin is the largest NOTE Confidence: 0.98466295 00:00:07.040 --> 00:00:08.639 organ in the body. And NOTE Confidence: 0.98466295 00:00:08.639 --> 00:00:09.679 not only is it a NOTE Confidence: 0.98466295 00:00:09.679 --> 00:00:10.960 barrier, but it has a NOTE Confidence: 0.98466295 00:00:10.960 --> 00:00:12.875 very active immune system. When NOTE Confidence: 0.98466295 00:00:12.875 --> 00:00:14.014 we think of inflammatory NOTE Confidence: 0.9832467 00:00:14.315 --> 00:00:16.154 skin disorders, psoriasis, when we NOTE Confidence: 0.9832467 00:00:16.154 --> 00:00:17.994 think of atopic dermatitis, they NOTE Confidence: 0.9832467 00:00:17.994 --> 00:00:19.195 all have a component of NOTE Confidence: 0.9832467 00:00:19.195 --> 00:00:20.414 skin barrier disruption. NOTE Confidence: 0.99636734 00:00:20.794 --> 00:00:21.755 And so many of the NOTE Confidence: 0.99636734 00:00:21.755 --> 00:00:23.595 diseases in dermatology become a NOTE Confidence: 0.99636734 00:00:23.595 --> 00:00:25.994 vicious cycle between skin barrier NOTE Confidence: 0.99636734 00:00:25.994 --> 00:00:27.454 disruption and inflammation. NOTE Confidence: 0.9948054 00:00:28.300 --> 00:00:30.380 Patients also experience things like NOTE Confidence: 0.9948054 00:00:30.380 --> 00:00:30.880 itch, NOTE Confidence: 0.9883549 00:00:31.260 --> 00:00:33.340 burning, stinging, and it affects NOTE Confidence: 0.9883549 00:00:33.340 --> 00:00:34.940 their quality of life. And NOTE Confidence: 0.9883549 00:00:34.940 --> 00:00:36.320 my job as the scientist NOTE Confidence: 0.9883549 00:00:36.540 --> 00:00:38.300 is understanding how to break NOTE Confidence: 0.9883549 00:00:38.300 --> 00:00:39.280 this loop. NOTE Confidence: 0.9759062 00:00:45.575 --> 00:00:46.935 In the big picture, my NOTE Confidence: 0.9759062 00:00:46.935 --> 00:00:48.375 laboratory is doing what is NOTE Confidence: 0.9759062 00:00:48.375 --> 00:00:50.375 called structural biology. We are NOTE Confidence: 0.9759062 00:00:50.375 --> 00:00:52.075 trying to understand the structure NOTE Confidence: 0.9759062 00:00:52.215 --> 00:00:53.595 of how proteins, NOTE Confidence: 0.9873749 00:00:54.055 --> 00:00:55.910 nucleic acids, and other macromolecules NOTE Confidence: 0.97278315 00:00:56.449 --> 00:00:57.969 work in the skin and NOTE Confidence: 0.97278315 00:00:57.969 --> 00:00:59.969 how drugs that target different NOTE Confidence: 0.97278315 00:00:59.969 --> 00:01:01.969 skin diseases work. And then NOTE Confidence: 0.97278315 00:01:01.969 --> 00:01:03.730 in certain genetic diseases where NOTE Confidence: 0.97278315 00:01:03.730 --> 00:01:04.869 those proteins NOTE Confidence: 0.99069744 00:01:05.170 --> 00:01:06.770 are in error, we want NOTE Confidence: 0.99069744 00:01:06.770 --> 00:01:08.130 to understand what has gone NOTE Confidence: 0.99069744 00:01:08.130 --> 00:01:09.409 wrong and how can we NOTE Confidence: 0.99069744 00:01:09.409 --> 00:01:09.735 fix NOTE Confidence: 0.99456376 00:01:10.535 --> 00:01:11.575 it. There's no one else NOTE Confidence: 0.99456376 00:01:11.575 --> 00:01:12.315 in dermatology NOTE Confidence: 0.9929727 00:01:12.855 --> 00:01:14.315 that is running a primary NOTE Confidence: 0.9929727 00:01:14.375 --> 00:01:16.935 NIH funded research lab that's NOTE Confidence: 0.9929727 00:01:16.935 --> 00:01:18.855 dedicated to structural biology and NOTE Confidence: 0.9929727 00:01:18.855 --> 00:01:20.075 answering those difficult NOTE Confidence: 0.9995214 00:01:20.375 --> 00:01:20.875 biochemistry NOTE Confidence: 0.9415083 00:01:21.175 --> 00:01:23.255 questions through the approaches of NOTE Confidence: 0.9415083 00:01:23.255 --> 00:01:24.075 extra crystallography, NOTE Confidence: 0.96317565 00:01:24.880 --> 00:01:26.880 cryo electron microscopy, and if NOTE Confidence: 0.96317565 00:01:26.880 --> 00:01:29.459 needed, nuclear magnetic resonance imaging. NOTE Confidence: 0.90512323 00:01:33.440 --> 00:01:34.660 So extra crystallography NOTE Confidence: 0.992693 00:01:35.040 --> 00:01:36.560 is a particular technique that NOTE Confidence: 0.992693 00:01:36.560 --> 00:01:37.600 allows you to understand the NOTE Confidence: 0.992693 00:01:37.600 --> 00:01:39.045 atomic level structure NOTE Confidence: 0.98488617 00:01:39.604 --> 00:01:41.765 of proteins, nucleic acids, and NOTE Confidence: 0.98488617 00:01:41.765 --> 00:01:42.505 their complexes. NOTE Confidence: 0.9964226 00:01:43.525 --> 00:01:44.325 What you have to do NOTE Confidence: 0.9964226 00:01:44.325 --> 00:01:45.685 in crystallography is take a NOTE Confidence: 0.9964226 00:01:45.685 --> 00:01:47.705 very pure protein, for example, NOTE Confidence: 0.9964226 00:01:47.765 --> 00:01:48.645 and put it in the NOTE Confidence: 0.9964226 00:01:48.645 --> 00:01:49.545 right solution NOTE Confidence: 0.99620914 00:01:49.845 --> 00:01:51.145 that allows it to precipitate. NOTE Confidence: 0.98361063 00:01:51.924 --> 00:01:52.965 And when it does it NOTE Confidence: 0.98361063 00:01:52.965 --> 00:01:54.325 just right, it forms a NOTE Confidence: 0.98361063 00:01:54.325 --> 00:01:56.460 crystal. And that crystal is NOTE Confidence: 0.98361063 00:01:56.460 --> 00:01:57.200 a perfectly NOTE Confidence: 0.9808655 00:01:57.500 --> 00:01:59.820 aligned lattice of lots and NOTE Confidence: 0.9808655 00:01:59.820 --> 00:02:01.179 lots of molecules of that NOTE Confidence: 0.9808655 00:02:01.179 --> 00:02:02.539 protein of interest. And then NOTE Confidence: 0.9808655 00:02:02.539 --> 00:02:04.000 when you hit that crystal NOTE Confidence: 0.9808655 00:02:04.219 --> 00:02:06.140 with x rays, that crystal NOTE Confidence: 0.9808655 00:02:06.140 --> 00:02:07.119 then diffracts NOTE Confidence: 0.9925673 00:02:07.435 --> 00:02:08.715 the light. And then what NOTE Confidence: 0.9925673 00:02:08.715 --> 00:02:09.514 we can do is use NOTE Confidence: 0.9925673 00:02:09.514 --> 00:02:10.014 mathematical NOTE Confidence: 0.98380727 00:02:10.315 --> 00:02:11.855 approaches to take that diffraction NOTE Confidence: 0.98380727 00:02:11.915 --> 00:02:13.595 pattern and turn it into NOTE Confidence: 0.98380727 00:02:13.595 --> 00:02:14.655 actually a three-dimensional NOTE Confidence: 0.99983895 00:02:15.115 --> 00:02:15.615 model NOTE Confidence: 0.9788263 00:02:15.915 --> 00:02:17.435 of that protein, and that NOTE Confidence: 0.9788263 00:02:17.435 --> 00:02:18.715 allows us to determine the NOTE Confidence: 0.9788263 00:02:18.715 --> 00:02:19.995 structure at that atom and NOTE Confidence: 0.9788263 00:02:19.995 --> 00:02:21.355 bond level. And then we NOTE Confidence: 0.9788263 00:02:21.355 --> 00:02:22.710 can take that information and NOTE Confidence: 0.9788263 00:02:22.710 --> 00:02:24.630 ask those critical questions. What NOTE Confidence: 0.9788263 00:02:24.630 --> 00:02:25.830 does this tell us about NOTE Confidence: 0.9788263 00:02:25.830 --> 00:02:27.210 helping the human patient? NOTE Confidence: 0.96867526 00:02:33.030 --> 00:02:34.389 One of the wonderful things NOTE Confidence: 0.96867526 00:02:34.389 --> 00:02:35.990 about being a physician scientist NOTE Confidence: 0.96867526 00:02:35.990 --> 00:02:36.790 is I get to see NOTE Confidence: 0.96867526 00:02:36.790 --> 00:02:37.965 what it's like in the NOTE Confidence: 0.96867526 00:02:38.364 --> 00:02:39.584 lab to make a discovery, NOTE Confidence: 0.96867526 00:02:39.724 --> 00:02:40.605 but I also get to NOTE Confidence: 0.96867526 00:02:40.605 --> 00:02:41.805 talk to patients face to NOTE Confidence: 0.96867526 00:02:41.805 --> 00:02:43.165 face. And I really get NOTE Confidence: 0.96867526 00:02:43.165 --> 00:02:45.025 an understanding of what matters NOTE Confidence: 0.96867526 00:02:45.165 --> 00:02:45.905 to them. NOTE Confidence: 0.9940075 00:02:46.205 --> 00:02:47.405 And the advantage of this NOTE Confidence: 0.9940075 00:02:47.405 --> 00:02:48.444 is it allows me to NOTE Confidence: 0.9940075 00:02:48.444 --> 00:02:49.805 then come back from a NOTE Confidence: 0.9940075 00:02:49.805 --> 00:02:51.905 translational perspective and understand NOTE Confidence: 0.9992671 00:02:52.205 --> 00:02:53.665 what is going to help NOTE Confidence: 0.99552894 00:02:54.180 --> 00:02:56.500 deliver better patient care. This NOTE Confidence: 0.99552894 00:02:56.500 --> 00:02:57.860 is also why I really NOTE Confidence: 0.99552894 00:02:57.860 --> 00:02:58.820 am excited to be a NOTE Confidence: 0.99552894 00:02:58.820 --> 00:03:00.419 part of clinical trials here NOTE Confidence: 0.99552894 00:03:00.419 --> 00:03:01.000 in dermatology NOTE Confidence: 0.9989852 00:03:01.300 --> 00:03:01.960 at Yale. NOTE Confidence: 0.99570644 00:03:03.220 --> 00:03:05.139 I love helping patients. I NOTE Confidence: 0.99570644 00:03:05.139 --> 00:03:06.740 love it when patients feel NOTE Confidence: 0.99570644 00:03:06.740 --> 00:03:08.100 better and are happier with NOTE Confidence: 0.99570644 00:03:08.100 --> 00:03:08.600 themselves. NOTE Confidence: 0.99634796 00:03:08.980 --> 00:03:10.284 In the end, all of NOTE Confidence: 0.99634796 00:03:10.284 --> 00:03:11.405 what we do, whether it's NOTE Confidence: 0.99634796 00:03:11.405 --> 00:03:12.465 the research mission, NOTE Confidence: 0.9935456 00:03:12.764 --> 00:03:14.125 the clinical mission, or even NOTE Confidence: 0.9935456 00:03:14.125 --> 00:03:15.724 a clinical trial mission, it's NOTE Confidence: 0.9935456 00:03:15.724 --> 00:03:18.144 all about advancing patient care, NOTE Confidence: 0.9935456 00:03:18.204 --> 00:03:19.965 developing new therapies for rare NOTE Confidence: 0.9935456 00:03:19.965 --> 00:03:21.644 genetic skin diseases for which NOTE Confidence: 0.9935456 00:03:21.644 --> 00:03:23.264 patients have nothing yet.