Ep.3 with Sarah Blagden: Stopping cancer before it starts

That is fascinating.

And before we go too much into your work in prevention itself, I mean, I just want to reflect that I believe that the time you were in that fruit fly lab was even before the whole genome, the human genome had been fully sequenced.

And so the world was obsessed with DNA.

But you saw even at that very early stage, the importance of RNA and the importance of RNA in cancer and in early detection.

So that's another example of you thinking very differently.

What inspired you to look at RNA? Maybe you could just explain to the listener why it turns out that RNA rather than DNA is such an important thing for us to be focusing on to understand the kind of invasiveness of a potential cancer.

Yeah, I think we all got into a very somatic mutation theory mindset as a community within oncology.

And I think it's understandable.

You know, I remember the excitement.

I was in, as you said, I was in the lab with the actual sequence of the Drosophila genome, the fruit fly genome, just before they did the human genome.

And it was so exciting to start realizing all of these things.

First of all, that the genome was a lot smaller than expected.

But interestingly, where you see the diversity is in the proteome.

So that was such an unresolved question to me.

Everything became about next generation sequencing and next, next generation sequencing.

And from what I could see in the lab, what was clearly going on, for example, with LARP1 and these other RNA binding proteins, is that they were distorting the genetic message.

So they're sort of like they're binding to RNA, mRNAs particularly, and they're actually completely changing the output.

So although there might be a protein that's encoded by a gene, it might not actually end up being encoded because the RNA binding proteins are interfering with that message, with that signaling.

And it turns out that that's a very kind of ancient and hardwired system we have in our bodies, that RNA binding proteins come in and they kind of micromanage or they perhaps even macromanage the genomic signature.

So this particularly happens in pre-cancer.

And there's a kind of really interesting perspective that I'm also looking at from our lab's point of view, is that actually just having a mutation in a cell is not enough.

Clearly, there's other things going on.

We know that there's inflammation.

We know that there's other pressures on cells that control how they respond to those pressures.

And one thing that seems to be coming out from the research that we're doing is that the cells are reverting to a very ancient state.