Hi My name is Michelle Dawson and

I've been at Georgia Tech since
November of two thousand and eight and

I am going to show a few slides from
the work that I did as a post doctoral

research fellow at Massachusetts General
Hospital working in the lab of cash.

Jane and then I'm going to go on and

tell you a little bit about the lab
that I started at Georgia tag.

So the work that I did at
Massachusetts General was focused

on looking at the role of bone marrow
drive cells and the growth of tumors and

the formation of metastasis and this image
shows I met a static tumor in the lungs

of a c fifty seven black six mouse and
you can see the medicine had a tumor in

the center of the portion of the slide and
these green cells are bone marrow

cells these bone marrow cells form
a really important portion of this

that a static tumor and that they align
these vessels stabilizing the vessels and

allowing for the continuous growth
of this matter static tumor.

So bone marrow cells
are views throughout our body

to heal wounded tissues and
to contribute to new growth and

in the case of a cancer where soluble
growth factors are released by the tumour

cells these soluble growth factors
move throughout the circulation and

they trigger cells in the bone marrow to
be released into the blood circulation is

released cells can move
through the bloodstream and

enter the tumor where they contribute
to the formation of new blood

vessels in the studies that I did
at Massachusetts General Hospital.

We used a bone marrow transplant mouse
model to look at the accumulation of these

bone marrow cells in
that a static tumors and

in our studies we used a c fifty
seven black six or an F.P.P.

mouse that was irradiated which
deflates the cells in the bone

marrow compartment we've been replaced
those cells with cells from a G.F.P.

positive mouse the new mouse then would
have bone marrow cells that express

the green fluorescent protein which would
allow us to track those cells in our.

Daddies.

These are some tissues that were isolated
from the bone marrow transplant mice.

These are spleen tissues kidney
liver muscle and lung and this

is a tumor tissue and on the bottom panel
you can see the tissues accumulated that

were isolated from the beta act in the
mouse which expresses G.F.P. constituent

evilly versus the bone marrow transplant
mouse and you can see in the bone marrow

transplant mouse there's only a few
bone marrow cells in normal tissues.

But if you look at a tumor tissue.

It's just loaded with bone marrow cells.

So the bone marrow cells are important to
the growth of tumors and they accumulate

very rapidly in those tumor tissues
helping this tumor to continue to grow.

There are different signalling pathways
that are involved in the process

of recruiting bone marrow cells to tumors

in our studies we were focused on the role
of that Jeff receptor one signally.

We looked at the effect of using different
antibodies to block this signal in pathway

on the accumulation of bone
marrow cells in the primary

tumor of the medicine addict tumor and
in different regions of the body.

This is a cartoon of the study that we did
in the lab we had a bone marrow transplant

mouse that was subcutaneously
implanted with tumor cells

with then treated this mouse
throughout the course of this study and

we looked at the accumulation of bone
marrow cells in the primary tumor.

We then they set up the primary tumor and
we looked at the accumulation of bone

marrow cells in the lungs prior to and
after the formation

of spontaneous metastasis these are some
tissues that were collected from our

studies we looked at the effect of these
bone marrow cells on the growth of Louis

lung carcinoma tumors and
of these sixteen F. one melanoma tumors.

We also looked at the accumulation
of these bone marrow cells

in the primary tumor at a port in
regions of the tumor including the tumor

muscle border were moved
task assist starts to begin.

We also looked at med a static
tumors that formed in the lungs.

So this is.

The data is that shows the accumulation of
bone marrow cells in the primary tumor and

we found that some of the antibodies that
we use in our studies were able to reduce

the accumulation of bone marrow cells in
the primary tumor but not all of them.

We also looked at accumulation of bone
marrow cells in the lungs in different

regions either in
the meadow static tumor or

in the tissues surrounding the medicine
where we were interested in determining

whether a medicine at a leads to
the formation of medicine attic tumors.

And we found that some of these antibodies
could reduce the accumulation of bone

marrow drive cells in the lungs and
in metastasis specifically.

We believe that this was in part to
the blocking of these soluble growth

factors that lead to the accumulation
of bone marrow cells.

We also looked at the effect of to look
condition media on the growth of tumors

and metastasis and
we wanted to determine whether the soluble

growth factors that are released by tumors
could increase that number of bone marrow

cells that accumulate or the formation
of metastasis and we found that

with the tumor condition media we had
more metastasis especially in melanoma.

Bear in mind.

And we also looked at the accumulation
of bone marrow cells but

surprisingly we didn't find that there
were more bone marrow cells in tumors but

we did find that there were
more met a static me shit.

So although the blockade.

So although the soluble growth factors
didn't increase the number of bone marrow

cells that accumulated in
a specific medicine attic tomorrow.

They increased the number of
medicine added to yours and

thereby the number of medicine
that Ignatius that had formed.

So I've just given you a few highlights of
the studies that I recently completed at

Mass General and since I've been here
I've started a lab that is focused on

looking at stem cells and how we can
engineer these as Gene delivery factors.

The stem cells that we're working
with are bone marrow derived stem

cells that are isolated from different
strains of life using lies in our studies

is important because then we can isolate
cells that arson Janay again we ran plant

them with tumors we can find out how these
cells will affect the immune response and

these are some slides illustrating
the different ways that we characterize

the cells that we isolate from
mice including using the colony

forming assayed to determine whether
these cells are able to regenerate and

using different differentiation assays
to be able to determine whether they can

differentiate into
different types of tissues.

Now we're interested in looking at how
soluble growth factors that are released

by tumors alter the migration
of melancholy will stem

cells that we would like to use
in our gene delivery of actors.

So in the set is that I
show here we use D.S.

red to transfer these cells which gives
us a label so we can identify ourselves.

You can see that they're all fluorescent
after the transportation with them looked

at the migration of these cells in a boy
didn't chamber assaye and we looked

at the effect of tumour condition
media on the migration of these cells.

We found that tumour condition
media increases the migration

of medicine from a stem cells using the
strands will migration assaye we also find

that it alters the morphology of these
cells and this was very interesting to us

since we're interested in determining if
soluble growth factors alter the side of

skeletal re ology of cells and to look
at the reality of cells we're going

to use the technique of multiple
particle tracking in this case particles

are embedded in the side of skeleton using
a ballistic particle injection system and

these are some polystyrene particles and
some novel particles that we might use in

our lab and we inject these
cells into the cytoplasm we then

measure the traces of their motion with
respect to time and from that information

we can get quantities such as the means
words placement with respect to time and

from this we can determine
the diffusion color vision and the.

Trickle properties of the region of
interest or the tracking region.

So I've told you a little bit
about the work that I finished at

Massachusetts General and
about work that I've just started here at

Georgia Institute of Technology the lab
that we're focused on developing

is interested in combining these
concepts of tumor biology biophysics and

stem cell biology to use us to be able
to be able to develop mess and kind

of stem cell Gene delivery systems that
can overcome current transport barriers.