Director of the Center for Structural Oncology at Penn State University.
Noteworthy: Her lab focuses on understanding small things in a big way and how problems within genes can lead to disease. Using a special freezing technique known as cryo-EM, Professor Kelly's lab is pioneering a new area of research they refer to as structural oncology.
Where to find her: LinkedIn | Twitter: @DebKellyLab
Cryo-EM is a powerful tool that helps look at cancer molecules differently. Penn State University uses the cryo-EM technique to understand and outsmart cancer. Professor Kelly explains, "Our lab uses a very high-tech imaging approach. It's called cryo-electron microscopy or cryo-EM, which pioneers in our field actually won the Nobel Prize for just a few years ago. And what we'd like to do is dive deep into cancer cells, understand what molecules look like using these instruments, take pictures and snapshots of them — what you would do with your iPhone but in portrait mode — so we can really focus very deeply on the nuances of these molecules. Then we use these molecules to try and better understand what goes wrong in cancer, how these molecules are to cancer, and what we might do to better inform treatments based on differences in molecules from cancer cells versus normal cells."
Cryo-electron microscopy allows us to image things at the level of atoms. So what makes cryo-EM technology so useful in cancer research? Professor Kelly says, "What cryo-EM does is it allows us to see all the molecules that constitute cells, their different placements within cells, as well as their over architecture down at the level of atoms. So going even deeper beyond just the level of cells, we can get down and understand the level of which proteins are with DNA, how these proteins don't interact with DNA properly to protect cells from diseases, or how things might work against us when cells become cancerous and how molecules go awry and don't perform their job properly."
What makes Penn State unique in cryo-EM? Professor Kelly explains what makes her lab's cryo-EM one of a kind. She says, "Cryo-electron microscopes that are installed and operational at Penn State are uniquely built to service the life science community as well as the material science community. And some of these instruments have different analytical tools and cameras integrated in them that you wouldn't find in any other cryo-EM instrument. We're looking to screen and look at proteins differently."
"It'd be really great if we could look at these structures and be able to stratify disease to help better predict disease outcomes. And if we can add that extra layer of information, I think we can give physicians and oncologists better tools to have these predictions and better inform treatment management plans. We want to be able to contribute at that level so we're down at the molecular toward the atomic scale of things to make the big picture of how we might be able to have better predictive measures in cancer."
"In addition to being able to see, at this high level of detail, the way proteins might interact with drugs, we want to understand how they are actually operating in a more dynamic sense. We're not all rigid; we're not all fixed. As you and I were speaking before this, we sequestered our dogs because our dogs don't just sit there quietly for us. They run around, and they do things. Understanding the dynamic nature of how these proteins run around and do things in our bodies — much like we want our dog to sit still, we also want the proteins to be in the body and do their proper job. So understanding how things operate properly, not just how they look, is equally important to jointly investigate."
"We started working in the biochemistry of this, and we figured if we started to look at the 3D structure of BRCA1, we might know a little more about what's going wrong in these cases with genetic mutations. So then, is there something we could do about it therapeutically to improve outcomes for women with breast cancer related to BRCA1, and BRCA1 mutations aren't the majority of female breast cancer, but most of them are most deadly. They're the ones that lead to metastasis. They're the most life-taking of very young women, and it's affecting a lot of underrepresented women in society."