(mellow music)
- Hi, Joseph.
It's great to have you here.
I understand that you're working on breast cancer,
and I'm wondering if you could tell us a little bit more
about exactly what you're trying to figure out.
- Something our lab is really fascinated by
is a process called collective invasion.
Essentially it's cancer cells actually moving together
in packs of cells rather than single cells.
And that's one area that we've been really fascinated by
because we didn't envision that cancer cells would actually
cooperate to move.
And so that's one process that currently we're trying to
understand further.
And not just that, but we're trying to also understand
why tumors actually have a lot of this diversity
in the first place.
Some cells do actually cooperate together when they move
and some cells actually move as a single cells.
So trying to understand what allows these cells
to move in either way
is definitely something we're interested in.
- So it sounds like tumor cells don't always invade
as a group.
Sometimes they do.
But if it's advantageous to invade as a group,
then how come it doesn't always happen?
- Yeah, we would envision that if it is really advantageous,
that cancer cells would move in groups that they would do it
in that way.
And that's actually one thing that we're really
intrigued by.
We actually find that single cells
we always find in tumors, that single cells do invade
out kind of on their own as well.
And we've always been curious as to why that's even present
in the first place.
And I think that's just because tumor cells,
for the most part,
they are very heterogeneous.
And what we mean by that is that there's a lot of diversity.
Even among breast cancer,
there's a lot of different subtypes.
We've also found that in a single tumor,
there's also a lot of different groups of cells
that do different things.
And so I really do like to think of a tumor
as kind of like a company,
where in some ways we have different,
even within a company,
there are some departments or some groups that over time
maybe lose their efficacy or they lose their function.
They're not really as useful anymore.
And you'd imagine that they kind of phase out.
And so in the same way, cells are very similar
in that through evolution,
some groups of cells, you would imagine
if they're not really as needed, they would not survive.
They would actually kind of phase out.
And so that's what we would imagine for single cells
that they're not as needed within a group within a tumor,
but we actually find that it's still there.
And so there must be a function
that these cells have
that is necessary for this tumor to grow and to invade.
And we're trying to understand why that's the case.
- It seems like systems biology is a great way to study
biological diversity that you were talking about.
And so I'm wondering if you could tell us a little bit
about what types of tools and approaches
that stem in systems biology
you're using to understand this sort of single cell
versus collective cancer cell migration.
- So one technique that our lab actually developed
is to actually take a single tumor and be able to actually
separate out different groups or different subpopulations,
as we like to call it, of cells that act differently.
And so something that we've already done
is we've taken a single tumor.
We've seen how they invade.
And we've noticed again,
that there are some cells that move in packs of cells
or through collective invasion
and some cells that elect not to move in that way.
And so we've actually used our technique to be able to
separate those cell populations out.
And what we've done is basically gene expression analysis.
And so what that means is we've actually looked to see
how the gene expression of these different groups of cells
are different.
And we've been trying to basically compare them to see
how they are different
and potentially using that information
we're trying to understand what roles each of these
subpopulations could be playing
for the whole tumor to eventually grow
and to invade and metastasize to a secondary site.
So that's something that we've been trying to do,
looking at these differences
and seeing what roles these cells might play.
- And have you found anything surprising?
- I think the most surprising thing
that we've been able to find
is that when we compare cells that invade cooperatively
versus cells that don't,
we found that cells that invade cooperatively actually
they produce a lot of cholesterol.
So that's really surprising to us
because for the most part in humans,
it's mostly liver cells that produce cholesterol.
Well, we're actually finding that breast cancer cells
that invade cooperatively,
they actually produce a good amount of cholesterol.
And this is interesting because
there are actually cholesterol reducing agents
that are FDA approved, called statins, that have been used
in breast cancer treatment in the past
but their efficacy has always been up and down.
Sometimes it works, sometimes it doesn't,
and it's been very inconsistent.
And maybe this illuminates
a little bit of why that might be the case
because of the fact that tumors are very diverse.
And maybe the fact that there are some tumors that will
invade cooperatively more
versus tumors that invade as single cells more,
that could be a reason why some statins could work
maybe for cooperatively invading tumors,
but not so much the ones that do not cooperate.
And so that's one thing that we're thinking about right now
and trying to figure out whether or not that correlation
is there and whether or not that's one reason why statins
might actually work for breast cancer treatment,
but only certain types of breast cancer treatment.
- Interesting.
I guess we'll have to keep our eyes open for that.
Hear what happens in the future.
So as I listen to you describe your research,
one of the things I find really fascinating
is that you are straddling the line between basic research,
which really is about how the cells work,
how they communicate to one another,
understanding those types of things, in the context
of breast cancer,
and then also translational research,
which is a lot more about what have we learned and
what can we then take to the bedside,
in terms of novel therapeutics
or diagnostic tools that can help patients.
What has motivated you to pursue this type of research?
- Intellectually, I think the idea of tumor diversity
or the fact that there's, in some ways,
kind of a community of cells that work together
to form a tumor.
I think the complexity of that was really fascinating to me.
And so that's definitely something that motivates me.
But also working in a hospital setting,
I think really reminds me of how real this disease is.
We know that for breast cancer patients,
one of the main things that leads to their death
is the fact that the breast cancer tumor
actually does invade and spread to a secondary site.
And so trying to find a way to stop this process,
or to mitigate this process
is definitely something that also fuels me
to try to understand what the differences are
and the different groups of cells that are present
and try to stop this process from happening
in the first place.
- Well, thanks so much for sharing your work with us.
- Of course, my pleasure.