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>> Hi. My name is Angelica Thetzlwolfo,
and I'm one of the two new faculties
that have been recruited to this Center for Sensory Methodology.
>> I have my primary appointment in the Department of
Neuroscience, but by heart I'm a developmental biologist.
So my laboratory studies how the auditory sensory epithelium
develops.
In particular, we are interested in how this beautiful array
of mechanosensory hair cells is established during development.
I don't know if you saw some of the images, but in the mammalian
in our cochlear, hair cells are arranged in rows.
So we have two different types of mechanosensory hair cells,
inner and outer hair cells, and
we have a single row of inner hair cells and
free rows of outer hair cells that stretched all the way,
all the length of the cochlear coil, and this is quite
remarkable to have such a precise arrangement of cells.
And such arrangement really demands a mechanism that ensure
the right number of cells are produced at the right time and
at the right place, and so over the last several years,
my laboratory was studying some of the molecular mechanisms that
are engaged in ensuring that these processes occur properly.
We found, for example, that a signaling pathway that allows
cells to communicate with each other, which we refer to as
notch signaling ensures that the right ratio of hair cells and
supporting cells are produced.
So, if you disrupt this pathway,
you over produce these mechanosensory hair cells, and
what happens is actually these cells will degenerate without
the support of the supporting cells.
Meaning that it is really critical to
get the fine balance of getting the number of cells right.
More recently, we also looked into the question of how
can you ensure that these cells are produced at the right time
at the right place, and we found that a highly conserved
signaling pathway, which consists of microproteins and
RNA binding proteins, the [INAUDIBLE]
instructs cells to stop dividing
and start differentiating at the right time, at the right place.
So you could now ask a question, Why do we care about
how the auditory sensory epithelium develops?
And I would say as a basic scientist,
that it's a fantastically beautiful question to ask.
Just because we want to know things,
we want to explore things.
But, of course, I'm proud of the medical school.
And there's another really important reason, and
that's human health.
You might know, or you might not know, but mechanosensory hair
cells are only produced once in our lifetime.
And we only have a limited number of these hair cells, so
in our inner ear cochlea we have about 10,000 hair cells, and
if hair cells are lost due to damage, that could
be loud sound, or to toxic drugs, or
even aging, they're lost forever, and that really
causes functional deficits and could cause deafness.
So, we think that learning about development might help us
in developing strategies for
regenerating these cells, and we think that because,
when you look at systems that do regenerate, very often, they
hijack developmental processes, so they kind of recapitulate,
the same process they would under go during development.
We also think that in particular,
the auditory sensory epithelium
Introducing cells from the outside might be hopeless.
The auditory sensory perfume is encapusled in bone, so
you can not really use, induce [INAUDIBLE] stem cells,
ES cells and graph them into the tissue.
We have to kind of reprogram existing cells, and my lab and
many other labs are focusing on a particular cell type,
the supporting cells.
The supporting cells, really, surround the air cells, and
they share a very close lineage relationship
with these air cells during development.
They derive from a common pool of progenitors, and
as I told you, pathways like notch signaling
partition that pore into hair cells and supporting cells.
And people now look into manipulating
these exact pathways to maybe force supporting cells to
transdifferentiate into hair cells in the mature tissue.
Another reason why people are really excited about supporting
cells is that in species that do regenerate,
these are the exact cell types that produce hair cells.
So birds for example,
have a very sophisticated ability to hear detect sound.
Their auditory sensory epithelium develops quite
similarly to ours, but in contrast to humans,
they do regenerate these hair cells.
And the supporting cells are actually getting reactivated
after damage to these cells and can function as progenitors.
And more recently, and that was part of my
study as post doctoral fellow, we found that even in mammals,
in our case we use the mouse as a model system, the supporting
cells have some intrinsic capacity to produce hair cells.
So, when you take them out of their normal environment,
put them in a culture dish, they can become like progenitors.
They start to divide again, and
they can differentiate into hair cells.
Meaning that maybe there are only a couple of factors
that limit their ability to regenerate hair cells, and
we think that by studying fundamental development,
we will get a toolbox that can be applied to maybe forcing
these supportive cells into becoming hair cells, and we hope
that future studies will maybe translate into Therapeutics.
Thank you.