Reprogramming in the Inner Ear: A Promising Path to Restore Hearing

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00:00:12.23 A priceless expression on little Harold’s face
00:00:15.21 as he hears sound for the first time in his life.
00:00:20.06 We all have seen videos of little babies
00:00:23.15 responding to their mother’s voice
00:00:25.09 when they hear it for the first time,
00:00:28.10 and those expressions, emotions, and feelings are simply priceless.
00:00:33.08 Most of us in our day-to-day lives
00:00:35.16 don’t really sit down to think about or appreciate
00:00:38.27 our sense of hearing,
00:00:40.29 and I’m here to tell you why you should be doing that.
00:00:44.21 So, how do we hear?
00:00:46.21 When sound waves enter our outer ear,
00:00:49.10 they pass through to the middle ear
00:00:51.20 and strike the eardrum, depicted in blue here.
00:00:56.03 From the eardrum,
00:00:57.27 the sound vibrations are transmitted to the middle ear bones,
00:01:01.12 which further transmit these vibrations
00:01:04.16 to the snail-shaped structure, in pink here,
00:01:06.29 called the cochlea.
00:01:09.08 Within the cochlea lies a flat sheet of sensory epithelium,
00:01:13.27 which comprises cells important for hearing
00:01:17.05 named the hair cells,
00:01:19.14 in yellow here.
00:01:20.29 Look at these hair cells in action.
00:01:23.06 These hair cells are actively sensing sound
00:01:26.11 in the rat inner ear.
00:01:28.27 When I say, “hair cells are actively sensing sound,”
00:01:32.00 what does that mean?
00:01:33.07 Hair cells convert sound waves into electrical messages.
00:01:37.08 Now, the way they do this is
00:01:39.07 when sound waves strike against the hairs,
00:01:43.06 or the projections on hair cells,
00:01:45.08 there is a deflection that is caused.
00:01:47.24 This deflection leads to the generation of electrical impulses,
00:01:52.13 which are then integrated from across all hair cells
00:01:56.23 in the organ of Corti
00:01:58.26 and passed on to the brain
00:02:01.17 through the auditory pathway for sound perception.
00:02:05.09 Now, that process is comparable to this Mexican wave, here —
00:02:09.03 somewhat.
00:02:11.03 Now, imagine that each individual here is a hair cell.
00:02:13.13 You see that they’re moving their hands
00:02:15.16 just like how hairs move on the hair cell.
00:02:19.09 Even though each individual is moving their hands,
00:02:22.22 and the movement is local,
00:02:24.09 you see that the wave,
00:02:26.11 and the information in the wave,
00:02:28.03 moves from one end to the other.
00:02:30.11 This is exactly how sound information
00:02:32.25 is transmitted from the ear to the hair cells,
00:02:35.25 and then the brain as well.
00:02:37.27 Now, coming to hearing loss,
00:02:39.20 the death of these important hair cells
00:02:41.24 is what causes hearing loss.
00:02:44.02 Hearing loss is important because it’s a major public health issue,
00:02:48.04 and 43 million Americans suffer from this condition,
00:02:51.18 and it’s the third most common disorder
00:02:54.01 in the United States.
00:02:57.09 There are a variety of factors
00:02:59.09 which contribute to hair cell death.
00:03:02.04 So, these include infection and injury, noise,
00:03:05.23 age, genetics,
00:03:07.20 some kinds of medications too.
00:03:10.25 What about treatment options? Are there any?
00:03:14.01 Cochlear implants and hearing aids
00:03:16.08 are available to manage hearing loss
00:03:18.27 but not really to treat it.
00:03:21.00 But regeneration of hair cells
00:03:23.16 is a potential future option to restore hearing,
00:03:26.22 and that’s what I’m going to tell you more about today.
00:03:30.02 What do we already know about regeneration?
00:03:33.15 We know that non-mammalian vertebrates,
00:03:36.10 like amphibians, fishes, and birds,
00:03:39.07 can regenerate their hair cells naturally.
00:03:42.20 Now, what you see here in front of you
00:03:44.24 is an image of the chicken inner ear.
00:03:48.19 And here you see hair cells are intact.
00:03:52.04 Now, on application of loud sound
00:03:54.20 and certain kinds of medications — antibiotics —
00:03:57.20 hair cells die.
00:04:00.05 And within just three weeks, there is regeneration,
00:04:04.16 and the hearing of the bird is also restored.
00:04:08.08 This is what we mean by natural regeneration.
00:04:11.20 What about mammals?
00:04:14.03 In the case of mammals, such natural regeneration of these hair cells
00:04:17.14 does not occur.
00:04:19.14 Now, this is a perfectly intact inner ear of the mouse,
00:04:24.09 and in the damaged condition,
00:04:26.15 the hair cell loss is permanent,
00:04:28.20 and so is the hearing loss.
00:04:31.16 Now, when we say we do experiments in mice,
00:04:34.20 especially when we have to study mammalian inner ear
00:04:38.29 hair cell regeneration,
00:04:40.17 we use mouse as the model organism,
00:04:42.27 so we need to access the mouse’s inner ear.
00:04:46.04 So, here’s a little bit of technical detail.
00:04:48.07 How do we start from the mouse
00:04:50.02 and get to the inner ear?
00:04:52.29 So, the mouse is 3.5 inches in length.
00:04:56.18 Zoom in closer, into the head region.
00:04:59.29 The box here indicates the bone containing the inner ear.
00:05:04.28 And once we isolate the bone,
00:05:07.29 we perform a dissection to dissect out the cochlea.
00:05:12.11 And from within this cochlea, further,
00:05:14.15 we microdissect that sensory epithelium
00:05:17.09 called the organ of Corti.
00:05:20.00 Now, this organ of Corti has the hair cells
00:05:23.00 and the non-sensory cells.
00:05:25.21 Now, most of the images further in this presentation
00:05:29.06 are going to be images of this organ of Corti,
00:05:33.00 comprising hair cells and other cells.
00:05:36.02 Remember, this is a very tiny structure because
00:05:38.02 — completely stretched out, as well —
00:05:40.08 this is just about 0.25 inches in length.
00:05:43.14 Now, coming to my research’s central question…
00:05:48.23 the question that I wanted to answer through my research was,
00:05:52.12 can we convert non-sensory cells
00:05:55.01 in the mouse inner ear into hair cells?
00:05:58.11 And I decided to answer this question by comparing results at two different time points:
00:06:05.22 one in young animals
00:06:06.25 and the other in slightly older animals.
00:06:09.04 So, this is comparable to a time point of
00:06:13.02 infant versus toddler when we talk about humans.
00:06:16.07 So, when we say non-sensory cells in the inner ear,
00:06:19.04 what do we mean?
00:06:20.18 What are we talking about?
00:06:22.15 Taking a step back and reminding you of structures,
00:06:24.22 if you remember that red sensory epithelium from the video
00:06:27.07 on which the hair cells were present,
00:06:30.03 if I cut a section through that tube
00:06:33.01 and I look at it from the side,
00:06:34.28 this is what it’s going to look like.
00:06:36.21 You’re going to see one row of inner hair cells,
00:06:38.19 three rows of outer hair cells,
00:06:40.12 as indicated by one inner hair cell
00:06:42.23 and three outer hair cells, here in dark grey.
00:06:46.17 And the remaining light gray cells
00:06:48.14 that you see surrounding these hair cells
00:06:50.20 are all the non-sensory cells
00:06:53.18 within the inner ear.
00:06:55.19 So, these are our target cells now.
00:06:59.17 So, what are we going to convert these non-sensory cells with?
00:07:03.27 We’re going to use a protein called ATOH1.
00:07:07.26 ATOH1 is a transcription factor protein,
00:07:10.14 meaning it binds to specific DNA regions
00:07:13.20 and induces the expression of hair cell-specific genes
00:07:18.21 in the inner ear.
00:07:20.10 So, how was ATOH1 even identified?
00:07:23.05 When scientists were studying
00:07:25.05 the development of hindbrain structures
00:07:27.24 in the mouse embryo,
00:07:30.15 they traced the expression of ATOH1
00:07:33.19 and found that ATOH1 is a hair cell fate specifier
00:07:39.08 in the mouse inner ear,
00:07:42.12 meaning all sensory cells
00:07:44.20 which express ATOH1 go on to become hair cells,
00:07:46.29 and all those cells that don’t express ATOH1
00:07:50.11 remain non-hair cells.
00:07:52.21 It’s as simple as that.
00:07:55.02 So, now we know that ATOH1
00:07:57.04 is what we’re going to use.
00:07:58.23 So, how are we going to do this whole process of switching on ATOH1
00:08:02.28 in non-sensory cells?
00:08:05.09 We’re going to use a tool called the Cre-loxP tool.
00:08:08.22 So, the Cre-loxP tool is used
00:08:11.08 to switch on specific genes in specific tissues in mice.
00:08:16.07 Now, imagine a situation where I give you instructions
00:08:18.25 to go into your home,
00:08:21.02 go to a particular room within your home,
00:08:23.14 and switch on a particular light.
00:08:26.14 The same way, the Cre-loxP system works.
00:08:28.28 There, your home is the mouse’s body,
00:08:32.16 me giving you instruction is the injection
00:08:35.27 of a compound called tamoxifen
00:08:37.23 at the required time point within the mouse,
00:08:40.14 and you following this instruction
00:08:43.18 and doing the task is the Cre protein,
00:08:45.19 which is also present within the mouse.
00:08:48.07 And the Cre protein now goes to a specific tissue
00:08:52.18 — in this case, that tissue is your specific room —
00:08:57.03 and that light that you turn on
00:08:59.15 is the specific gene that is turned on —
00:09:01.10 in our case, this is ATOH1.
00:09:04.07 So, using the Cre-loxP tool,
00:09:06.17 non-sensory cells are going to have ATOH1 switched on in them
00:09:10.20 at a particular time point,
00:09:12.22 which is in one-day-old mice.
00:09:15.17 So, in one day old mice,
00:09:17.20 when ATOH1 is switched on in non-sensory cells,
00:09:20.21 this is what you get.
00:09:22.09 So, this is a confirmatory image
00:09:24.13 of successful switching on of ATOH1
00:09:26.25 in a variety of non-sensory cells
00:09:28.29 in the inner ear.
00:09:31.08 So, when we switch on ATOH1
00:09:34.01 and give it some time,
00:09:35.11 what do we see?
00:09:37.02 Well, what you see…
00:09:38.29 what we see is pretty amazing because
00:09:41.04 when we switched on ATOH1 in one-day-old mice
00:09:44.02 and analyzed the ears of these mice a week later,
00:09:48.24 what we saw was that
00:09:51.02 a large number of non-sensory cells
00:09:53.06 had converted into hair cell-like cells.
00:09:56.11 Now, I would like to call these hair cell-like cells
00:09:59.11 “reprogrammed hair cells”.
00:10:01.27 This was a pretty exciting result for me.
00:10:04.23 I was sitting in front of this microscope
00:10:07.21 staring at this very screen at this very result
00:10:10.16 three years ago,
00:10:12.07 and that moment has been one of my best PhD moments so far.
00:10:18.10 So, the next question that I asked from this result was,
00:10:23.22 how good are these reprogrammed hair cells,
00:10:25.20 especially when we compare them with normal hair cells?
00:10:30.21 The first experiment I did here
00:10:33.04 for answering that question
00:10:34.26 was to look at the hair bundle structure and morphology.
00:10:39.08 So, to do that, we collaborated
00:10:43.07 with another lab at the University of Michigan,
00:10:45.22 and they performed a technique
00:10:48.04 called the scanning electron microscopy technique
00:10:50.17 and captured some images for us.
00:10:52.27 And what we saw was that
00:10:55.18 the hair bundles present on a reprogrammed hair cell
00:10:59.05 were very similar to those of the hair bundles
00:11:02.23 present on a normal hair cell,
00:11:04.26 so they were alike,
00:11:06.14 and this was very encouraging to begin with.
00:11:09.27 Next, if hair bundles are similar,
00:11:11.23 is it possible that reprogrammed hair cells
00:11:15.28 also have sound-sensing activity channels?
00:11:19.10 So, to answer this question,
00:11:20.28 I performed an experiment
00:11:22.28 called the FM 1-43 dye uptake experiment.
00:11:25.08 Now, the principle of this experiment is simple.
00:11:28.02 Any cell which has sound-sensing activity channels
00:11:31.20 simply takes up this FM 1-43 dye
00:11:34.23 and is fluorescent.
00:11:38.08 And this time frame is as short as 10 seconds.
00:11:42.02 So, when I performed this dye update experiment,
00:11:44.21 I saw that all the reprogrammed hair cells
00:11:47.13 took up the dye within 10 seconds and were fluorescent.
00:11:50.14 So, this gave us the confidence
00:11:52.20 that the reprogrammed hair cells
00:11:55.12 did have some sound-sensing activity channels
00:11:58.20 present in them.
00:12:00.14 Now, the next set of characterization I did
00:12:03.04 of these reprogrammed hair cells
00:12:05.07 was based on markers:
00:12:07.14 immunostaining for markers.
00:12:09.16 So, the first set of markers
00:12:12.28 I did the staining for was specific to inner hair cells
00:12:16.23 and outer hair cells.
00:12:18.10 Now, taking a step back,
00:12:20.06 how do inner hair cells and outer hair cells compare with each other?
00:12:23.06 Now, even though both of them are hair cells,
00:12:25.28 inner hair cells receive 95% of the innervations
00:12:29.22 within the cochlea.
00:12:32.21 Basically, they get 95% of the load of the neuronal projections
00:12:36.10 within the cochlea,
00:12:38.02 and the remaining 5% goes to the outer hair cells.
00:12:41.19 So, when we did the immunostaining,
00:12:44.19 what we saw was that
00:12:46.20 all these reprogrammed hair cells that we were making
00:12:50.05 by switching on ATOH1
00:12:52.12 were in fact inner hair cell-like cells,
00:12:54.26 because they stained positive for the inner hair cell marker
00:12:57.23 and not for the outer hair cell marker.
00:13:00.18 So, that was encouraging.
00:13:02.13 Now, we decided to do the opposite,
00:13:04.17 where we wanted to see if every reprogrammed hair cell
00:13:07.13 attracted its own neuronal projection
00:13:10.05 to form connections with them.
00:13:13.20 And when we checked for the presence of these neuronal projections,
00:13:17.10 we saw that, indeed,
00:13:20.14 these reprogrammed hair cells were able to form such connections
00:13:24.23 and collectively they were innervated.
00:13:27.11 So, all of these results sort of told us
00:13:30.19 that these reprogrammed hair cells
00:13:33.00 that were coming up were very similar
00:13:35.28 to normal hair cells.
00:13:38.10 The next question that we asked was,
00:13:40.10 does switching on ATOH1 recapitulate developmental events?
00:13:44.11 Now, let me take a step back and explain something.
00:13:47.12 So, during the development of the organ of Corti
00:13:50.08 in a mouse embryo,
00:13:52.09 what happens is for every hair cell that comes up
00:13:56.13 there are specific adjacent supporting cells that come up.
00:13:59.08 Now, the function of the supporting cells
00:14:01.04 is to maintain and help
00:14:03.14 in the function of the hair cells.
00:14:05.01 Even though they are not sensory themselves,
00:14:07.05 they help in the maintenance and function
00:14:09.09 of the hair cells that they line.
00:14:12.23 The image in front of you, here,
00:14:14.06 is the base of an inner hair cell that you’re looking at.
00:14:18.11 And as you see, there are two unique supporting cells,
00:14:21.28 the inner border and inner phalangeal cells, here,
00:14:24.21 which line the inner hair cell.
00:14:26.13 Similarly, outer hair cells have their supporting cells too.
00:14:30.08 So, what we wanted to know was,
00:14:33.19 if these reprogrammed hair cells
00:14:36.16 were more inner hair cell-like,
00:14:38.02 does that mean they have unique supporting cells,
00:14:41.08 specific supporting cells, coming up too?
00:14:44.12 To test this, we stained for
00:14:47.02 the inner phalangeal markers,
00:14:48.24 and we were surprised to see that
00:14:51.16 for every reprogrammed hair cell that came up
00:14:54.07 there were adjacent inner phalangeal cells too.
00:14:56.29 So, this told us two things.
00:14:59.13 One is that switching on ATOH1
00:15:01.08 also recapitulated developmental events,
00:15:03.28 and two, that non-sensory cells
00:15:07.01 not only responded to ATOH1
00:15:10.01 by converting into hair cell-like cells,
00:15:12.08 but they also converted into
00:15:14.16 unique types of supporting cells.
00:15:17.22 So, this was overall very encouraging for us.
00:15:20.25 So with that, I’ll summarize the first part of my work
00:15:23.25 by saying that when we did
00:15:26.03 an extensive characterization
00:15:28.27 of these ATOH1-mediated reprogrammed hair cells
00:15:31.29 obtained from non-sensory cells,
00:15:34.27 we saw that these hair cells had mature hair bundles,
00:15:38.11 they had sound-sensing channel activity,
00:15:41.06 they were inner hair cell-like,
00:15:43.08 they were innervated,
00:15:45.02 and they had adjacent supporting cells regenerate too.
00:15:49.26 Okay, so coming back to that central research question,
00:15:53.22 what about the next time point?
00:15:56.02 What happens when the animals are slightly older?
00:15:59.16 Are we still able to use ATOH1
00:16:01.22 and get reprogrammed hair cells,
00:16:03.19 or is something different going on?
00:16:05.29 So, if you remember,
00:16:08.14 in the first set of experiments
00:16:11.03 we activated or switched on ATOH1
00:16:13.17 when the mouse was one day old.
00:16:15.22 But in the next set of results
00:16:17.24 that I’m going to show you,
00:16:19.08 the activation was done when the mouse
00:16:21.15 was one week old,
00:16:23.13 and the analysis was done a week after that,
00:16:26.09 when the mouse was two weeks old.
00:16:29.05 So, when we activated ATOH1
00:16:32.08 at one week old and analyzed at two weeks,
00:16:35.16 we were surprised to see that
00:16:38.01 a switch in just one week of age
00:16:41.25 showed absolutely no reprogramming effects at all.
00:16:46.13 We did not see reprogrammed hair cells
00:16:48.20 come up at two weeks in the older mice.
00:16:51.17 So, this was really surprising
00:16:53.21 because this told us that ATOH1
00:16:55.23 basically did not have the ability
00:16:58.11 to produce reprogrammed hair cells
00:17:00.22 when the animals were slightly older.
00:17:04.03 Now, what could the reason be for such an observation?
00:17:08.05 We went back to read some papers,
00:17:10.15 to discuss, and think about
00:17:12.28 what may be going on here.
00:17:14.28 So, ATOH1 acts in combination
00:17:17.24 with other factors in multiple different tissues
00:17:22.01 to bring about specific cell fates.
00:17:24.05 This is known.
00:17:26.17 So, ATOH1 is not unique to the inner ear;
00:17:29.05 ATOH1 is known to be involved in specification and expression
00:17:34.11 in granular neuron cells in the cerebellum,
00:17:36.27 secretory cells in the gut, and so on.
00:17:39.15 So, is it possible that we need
00:17:42.23 additional factors to act with ATOH1?
00:17:44.28 Only then, maybe,
00:17:47.14 the reprogramming will happen in older animals?
00:17:50.10 Well, we had to test all this out.
00:17:52.09 So, what we did in our lab
00:17:54.25 was we generated these three mouse lines.
00:17:57.09 Now, these three mouse lines, basically,
00:17:59.18 are combinations of these three factors.
00:18:03.19 So, the first line, A, is just ATOH1.
00:18:07.15 It’s very similar to what I have been talking about all along.
00:18:11.28 The second one is GFI1/ATOH1,
00:18:14.12 and the third one is GFI1/ATOH1/POU4F3.
00:18:17.23 Now, GFI1 and POU4F3
00:18:20.18 are two targets (downstream targets) of ATOH1,
00:18:24.20 and both these are transcription factors too,
00:18:27.05 and they are known to be important
00:18:29.10 for the maintenance and survival of hair cells
00:18:31.19 in normal inner ear development and older animals.
00:18:38.14 So, we know that both these genes
00:18:41.00 are important for hair cells to be hair cells.
00:18:45.10 So, the logic behind using GFI1, ATOH1, and POU4F3
00:18:51.01 is such that all three genes have an important role to play
00:18:55.21 in the life of a hair cell.
00:18:57.27 So, that said, the different combinations here,
00:19:00.11 as you can see,
00:19:02.03 do not really involve an ATOH1/POU4F3 combination.
00:19:05.11 This is because both are proneural genes,
00:19:08.08 and we really did not want to test
00:19:12.07 two proneural genes,
00:19:14.14 because it will simply lead to an additive effect
00:19:16.14 of the individual factors in question,
00:19:19.06 that is, ATOH1 and POU4F3.
00:19:21.07 So, we decided to just stick to these three combinations
00:19:23.23 and see what we get.
00:19:26.14 So, when a similar kind of Cre-loxP activation was done.
00:19:31.15 So, when I say “activation”, we are switching on these factor combinations
00:19:34.08 in the non-sensory cells again,
00:19:36.17 but this time in older animals.
00:19:38.24 What we see here, as depicted by the arrow,
00:19:41.07 is only in the three-factor condition
00:19:44.00 — that is, when ATOH1, POU4F3 and GFI1
00:19:46.27 were switched on together —
00:19:49.11 did we see a large number of reprogrammed hair cells.
00:19:53.15 But in the case of just the ATOH1 and GFI1/ATOH1,
00:19:56.08 we didn’t see reprogrammed hair cells come up at all.
00:19:59.20 This was a surprising result that we saw.
00:20:02.24 Now, we went ahead and characterized
00:20:05.11 these older reprogrammed hair cells again,
00:20:07.19 which came up in the three-factor condition,
00:20:09.20 and what we saw was that
00:20:12.17 these older reprogrammed hair cells
00:20:14.20 did not stain positive
00:20:17.13 for inner hair cell or outer hair cell markers.
00:20:19.27 So, the arrows here indicate the reprogrammed hair cells,
00:20:23.04 and you can see that they don’t stain positive
00:20:25.23 for either hair cell type.
00:20:27.12 So, what does this mean?
00:20:29.01 Does it mean that they are more immature?
00:20:31.04 Well, we don’t really know.
00:20:32.29 However, we still went on and characterized
00:20:35.14 these hair cells for some other properties,
00:20:37.17 just like before.
00:20:39.03 We saw that the older reprogrammed hair cells
00:20:41.10 are innervated, meaning they attracted neuronal projections
00:20:44.17 to form these connections,
00:20:46.09 and that they also had…
00:20:50.18 there was also evidence for the presence
00:20:54.22 of unique supporting cells
00:20:56.21 lying adjacent to them,
00:20:58.23 by the sheer density of the inner phalangeal marker staining
00:21:02.23 that we saw, indicated by arrows here again.
00:21:05.18 So, all of this still tells us
00:21:08.20 that maybe these three-factor induced reprogrammed hair cells
00:21:11.16 are still immature.
00:21:13.27 However, we are still doing some experiments
00:21:16.17 to analyze what these older reprogrammed hair cells are like
00:21:22.15 and what is different between these reprogrammed hair cells
00:21:25.17 and the one-week reprogrammed hair cells
00:21:28.28 that we got before.
00:21:31.08 So, to summarize this part of my talk,
00:21:33.12 I want to show you this representation here.
00:21:37.02 So simply, what you’re saying here
00:21:39.09 is that whenever you give non-sensory cells
00:21:42.03 in older animals just ATOH1,
00:21:45.12 they are unable to scale that regeneration roadblock,
00:21:49.15 indicated in red,
00:21:50.23 and there are no reprogrammed hair cells
00:21:53.03 produced after one week.
00:21:55.18 However, when the same non-sensory cell
00:21:58.16 has all three transcription factors
00:22:01.15 — ATOH1, GFI1, and POU4F3 —
00:22:04.05 switched on in them,
00:22:05.29 they’re able to scale this regeneration roadblock
00:22:08.18 and turn into reprogrammed hair cells
00:22:13.10 within one week time.
00:22:15.26 So, with that, this work also opens up
00:22:19.06 a lot of other additional questions
00:22:21.18 like, okay, you’re getting all these reprogrammed hair cells
00:22:24.04 in young animals as well as in slightly older animals,
00:22:27.16 so how long do they survive?
00:22:30.13 Can they hear — are they functional?
00:22:32.04 What about adding many other factors
00:22:35.11 to get more reprogrammed hair cells?
00:22:38.06 What about the frequencies that these hair cells can hear?
00:22:41.04 And so many other such questions.
00:22:43.23 Well, we don’t have the answers
00:22:46.00 to any of these right now,
00:22:47.20 and that’s for the field to take forward in the future.
00:22:51.19 Now, as I said before,
00:22:53.19 hearing aids and cochlear implants
00:22:56.06 are strategies that are available now
00:22:58.19 to manage hearing loss in humans.
00:23:01.18 However, we hope that through this work
00:23:04.13 we will be able to have fine tuning in gene therapy approaches
00:23:11.21 to treat human hearing loss in the future
00:23:15.19 by employing these reprogramming factors in question,
00:23:18.15 that is, ATOH1, GFI1, and POU4F3.
00:23:21.10 And hearing restoration is important
00:23:24.08 for an enhanced quality of life,
00:23:26.16 be it in the young or in the old.
00:23:29.18 Thank you all for listening to this talk today.

This Talk

Speaker: Amrita A. Iyer

Audience:

Student
Educators of Adv. Undergrad / Grad
Researcher
Educators

Recorded: December 2020

Talk Overview

Hearing loss, caused by the death of hair cells in the inner ear, is the third most common public health issue in the United States. Currently, there are no therapeutic strategies to restore hearing. In her thesis research, Dr. Amrita A. Iyer investigated the possibility of regenerating functional hair cells by reprogramming non-hair cells of the mouse inner ear. She found that overexpression of a single transcription factor, ATOH1, can successfully reprogram non-sensory cells into hair cells with typical characteristics in neonatal mice. However, a combination of three transcription factors – ATOH1, GFI1, and POU4F3 – was required to reprogram inner hair cells in 1-week old mice. Her findings provide a window into the developmental and gene expression requirements for regeneration of inner ear hair cells in mammals, and may inform future therapeutic strategies for hearing loss in humans.

Speaker Bio

Amrita A. Iyer

Dr. Amrita A. Iyer grew up in Bangalore in a home atmosphere that instilled in her a love for science and maths. After completing her schooling at Sri Kumaran Childrens Home (CBSE), she went on to pursue B.Tech in Biotechnology from VIT, Vellore. During the summer holidays of her bachelors, she did an industrial internship… Continue Reading

Credits

Brittany Anderton (iBiology): Producer
Eric Kornblum (iBiology): Videographer
Rebecca Ellsworth (iBiology): Editor
Jiefei Yuan (iBiology): Editor
Chris George (iBiology): Graphics
Maggie Hubbard (iBiology): Graphics

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Amrita A. Iyer

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