WEBVTT 1 00:00:00.550 --> 00:00:03.133 (upbeat music) 2 00:00:09.879 --> 00:00:12.734 line:15% There are an estimated 39.5 million people 3 00:00:12.734 --> 00:00:15.589 line:15% affected with asthma in the United States today. 4 00:00:15.589 --> 00:00:17.749 line:15% And asthma is estimated to cost the US 5 00:00:17.749 --> 00:00:20.869 roughly 76 to 80 billion dollars each year. 6 00:00:20.869 --> 00:00:23.180 Now interestingly, only about five to 10 percent 7 00:00:23.180 --> 00:00:25.741 of asthmatics actually count for over 50% 8 00:00:25.741 --> 00:00:27.749 of the total asthmatic cost 9 00:00:27.749 --> 00:00:30.398 and this group is known as the severe asthmatics. 10 00:00:30.398 --> 00:00:32.421 They are characterized by being poorly responsive 11 00:00:32.421 --> 00:00:35.748 to inhaled corticosteroids and bronchodilators. 12 00:00:35.748 --> 00:00:38.038 My research focuses on the hypothesis 13 00:00:38.038 --> 00:00:40.846 that horses affected with a severe asthma-like disease 14 00:00:40.846 --> 00:00:42.668 called equine pasture asthma, 15 00:00:42.668 --> 00:00:45.046 are able to serve as translational models 16 00:00:45.046 --> 00:00:47.577 for finding novel therapeutic targets of asthma 17 00:00:47.577 --> 00:00:50.468 specifically to decrease airway hyper-responsiveness, 18 00:00:50.468 --> 00:00:52.734 which is one of the key features of asthma. 19 00:00:52.734 --> 00:00:54.548 In work previously done by our lab, 20 00:00:54.548 --> 00:00:56.926 we have found that horses affected with EPA 21 00:00:56.926 --> 00:01:00.026 respond to airway spasmogens at diagnostic levels 22 00:01:00.026 --> 00:01:02.826 that are used to diagnose severe adult asthmatics. 23 00:01:02.826 --> 00:01:05.278 This is important because traditional animal models 24 00:01:05.278 --> 00:01:06.846 of asthma, like mice and rats, 25 00:01:06.846 --> 00:01:09.717 require much higher doses of those airway spasmogens 26 00:01:09.717 --> 00:01:11.244 to reach those same levels, 27 00:01:11.244 --> 00:01:13.118 making it really difficult to evaluate 28 00:01:13.118 --> 00:01:14.878 any new drugs done on these models 29 00:01:14.878 --> 00:01:18.028 that aim at reducing that airway hyper-responsiveness. 30 00:01:18.028 --> 00:01:19.585 So to that end, we then took horses 31 00:01:19.585 --> 00:01:21.977 that were affected with EPA and non-affected 32 00:01:21.977 --> 00:01:23.668 and we took surgical lung samples, 33 00:01:23.668 --> 00:01:26.561 as you see in the first picture here, 34 00:01:26.561 --> 00:01:29.202 and we were able to dissect out those lung samples 35 00:01:29.202 --> 00:01:32.312 and sequence MRNA looking for protein coding genes 36 00:01:32.312 --> 00:01:33.665 that specifically increased 37 00:01:33.665 --> 00:01:36.185 beta two adrenergic receptor signaling. 38 00:01:36.185 --> 00:01:37.873 Now that's important because beta two 39 00:01:37.873 --> 00:01:41.055 adrenergic receptor signaling is required 40 00:01:41.055 --> 00:01:43.833 to actually develop the asthmatic phenotype. 41 00:01:43.833 --> 00:01:46.265 We were able to find one gene that did just that 42 00:01:46.265 --> 00:01:47.895 and it was of particular interest to us 43 00:01:47.895 --> 00:01:50.384 because it has been shown to actually modulate 44 00:01:50.384 --> 00:01:52.615 the cell membrane potential in the heart 45 00:01:52.615 --> 00:01:55.855 and able to actually effect when your heart contracts. 46 00:01:55.855 --> 00:01:57.804 So we then wanted to see where that gene 47 00:01:57.804 --> 00:01:59.524 was expressed in our horses 48 00:01:59.524 --> 00:02:02.053 and we saw that in horses affected with EPA, 49 00:02:02.053 --> 00:02:04.654 versus not, that gene was actually expressed 50 00:02:04.654 --> 00:02:06.351 in the airway smooth muscle 51 00:02:06.351 --> 00:02:08.393 more than in controlled horses. 52 00:02:08.393 --> 00:02:09.603 We then wanted to know what would happen 53 00:02:09.603 --> 00:02:11.483 if we blocked that gene in bronchial rings 54 00:02:11.483 --> 00:02:14.384 that were dissected from horses affected with EPA, 55 00:02:14.384 --> 00:02:17.486 and we suspended those rings in a tissue-backed medium 56 00:02:17.486 --> 00:02:19.438 that received increasing concentrations 57 00:02:19.438 --> 00:02:21.817 of an airway spasmogen. 58 00:02:21.817 --> 00:02:24.547 So we did just that and we saw that in the genes 59 00:02:24.547 --> 00:02:26.834 that were actually received that blocker, 60 00:02:26.834 --> 00:02:29.164 they constricted to a much lesser extent 61 00:02:29.164 --> 00:02:30.455 than those that did not, 62 00:02:30.455 --> 00:02:32.506 showing us that this gene is important 63 00:02:32.506 --> 00:02:35.026 and looking at novel therapeutic targets for asthma 64 00:02:35.026 --> 00:02:36.466 and also shows us the importance 65 00:02:36.466 --> 00:02:38.723 of using animal models to study disease. 66 00:02:38.723 --> 00:02:41.306 (upbeat music)