Stephen J. Elledge, Ph.D.; Harvard Medical School; Innovator Award:

The DoD Innovator Award has allowed me to spend almost half of my effort on breast cancer and developing methods that will enable both my lab and other laboratories to attack the problem from a genetic point of view. And what we've been doing has been centered around developing the tools to turn off genes in human cells one at a time. And so what we're hoping to be able to do is to instead of guessing at the genes that you might want to inactivate to kill a tumor, we want the tumor to tell us what genes it needs to be a tumor. So if one at a time we can turn off a human gene and ask what sort of aspect of cancer now is no longer there, we can determine which genes are important for that. For example, the ability to proliferate or exist in an unusual location in your body - that's a characteristic of tumors. So we can find which genes those cells depend upon and those become drug targets. So it's a very unbiased way to look at potential drug targets for cancer therapies.

Another application of the methods that we've developed meshes well with some of the other sorts of approaches that people are taking to cancer, which are sort of the cancer genome atlas, which is an approach that takes a more physical view of the tumor to figure out how the genes are amplified or deleted. Once they find genes that appear to be for example amplified or over-expressed, you have to figure out which ones are the actual important ones in that group because a lot of genes are affected. And our methods which allow you turn off genes one at a time, allow you to test which of those genes are important. Alternatively, if you delete a gene and it makes you more cancer-like, we can turn off that gene in normal cells and ask did those cells become cancer-like and we can figure out which of the genes that are part of some relatively large deletion in the genome, which of those genes are the important genes that are contributing to the cancer phenotype.

Our lab collaborates very closely with that of Dr. Gregory Hannon's at Cold Spring Harbor and Greg was an Innovator Awardee. He got an Innovator Award I think a year before I did and he is an expert in this methodology called RNA Interference. He's one of the pioneers in that methodology and he and I met at Cold Spring Harbor and decided to join forces to try to make a library that would allow us to be able to control individual genes. And so the funding from the Innovator Award for both Greg and myself has allowed us to really push this area forward to the point where we're basically performing a genome project to design methods to turn off these genes. And so this has been a very close collaboration back and forth between my lab and Greg's lab now for over five years and it would not have been possible without the funding from the Innovator Award and the DoD.

The benefit of having funding like the Innovator Award allows me to train a number of individuals in these developing methods and technologies that can be applied to breast cancer and I've had several people from my laboratory go on and start their own laboratories to study breast cancer and several more are waiting in the wings to do the same. So it's actually paying for itself in dividends I think in the future by allowing us both the freedom to develop the new methods and the new ideas as well as training the people in how to use them so they can start their own laboratories and carry the tradition forward.