June 16, 2013 | by Wayne Lewis
As City of Hope celebrates its 100th anniversary, we offer a four-part interview with Art Riggs, Ph.D., chair of the Department of Diabetes and Metabolic Diseases Research. Many of City of Hope’s best-known breakthroughs came through his lab. In this series, he casts an eye back to some of his greatest scientific contributions — and forward to the advances on the horizon.
In Part 4, Riggs talks about his current work studying how to manipulate the development of stem cells, a line of research with implications for treating multiple diseases.
What are you working on today?
What I’m most excited about today is almost coming full circle from when I started out.
I started out studying the first transcription factor, the lac repressor. That was the very first protein that would bind to a very specific region of DNA. The repressor only binds right at the beginning of the β-galactosidase gene. It was 1967 to 1975 when I was working on that.
I’m now working on a technology that was just invented two years ago — not by me but by others.
It was scientists working on some obscure bacteria who discovered an easier way to make proteins that can bind to DNA. The incredible thing is, in about two weeks we can make a protein that will bind exactly where we want it on the DNA and will cut the DNA exactly where we want it.
|Art Riggs on why he loves his job:|
“I’ve got to be in the best occupation in the world. Most of the time, that’s the way I think.
“It’s intellectually exciting. We’re trying to solve puzzles, and cure disease. I’m an advocate for applying what we learn. That’s why I stay here at City of Hope.
“We’re really in an exciting area. I’m still able to do work that’s on the cutting edge. In sports, business, whatever, that’s when it’s at its best, is when you have the opportunity to do something important and you’re at the forefront of the field. What could be better?”
It’s actually a code that allows you to transfer from a DNA sequence to a protein. When you make this protein, it’ll bind only to that sequence. It can turn genes on and off. So we can design proteins that can turn genes on and off anywhere that we want in the genome. And it works in mammalian cells.
I’m working on this with a couple of people in my laboratory including a senior postdoc, Josh Tompkins. We’re trying to use that technology to do what we call epigenetic engineering. We’re engineering epigenetic changes into mammalian cells, and we expect those epigenetic changes to affect the differentiation of those cells from progenitor cells to adult cells.
To be able to do that is incredible. To be able to participate in that in my lifetime is exciting.
Now we’re taking the work I did in the late ‘60s and early ‘70s and combining it with epigenetics. It will be a whole new ball game. It will be transformational science.
We’re not the only ones doing it. There may be a handful already. So will we be the first? We’ll be right there at the forefront. That I do know.
What is the goal of this particular project?
The actual project would be to make heart cells, cardiomyocytes. That’s the system Josh Tomkins is working on. But it’s general, so if it works there it’ll work everywhere.
I’m working on another project that would be an application of the same technology: making insulin-producing cells, beta cells.
Essentially what you’re talking about is steering the development of stem cells.
That is exactly what I’m talking about. And it’s just amazing.