UT professor discusses her investigation on cell damage and its place in cancer research

Molecular genetics and microbiology professor Tanya Paull studies how cells respond to DNA damage and to a cellular imbalance called oxidative stress. Her research on cell damage has implications for cancer treatment as well as the treatment of ataxia-telangiectasia, a rare neurodegenerative disorder that inhibits movement and coordination. She is the winner of a CPRIT Cancer Prevention and Research Institute of Texas, or CPRIT, grant and one of 330 Howard Hughes Medical Institute investigators in the nation.

Daily Texan: What are you studying in your research now?
Tanya Paull: We primarily work on DNA damage response, which is a series of events that occur after double-strand breaks happen in chromosomal DNA. The chromosome is made up of a DNA double helix, a double-strand break occurs when the helix is severed into multiple pieces. Cells have ways of recognizing, binding to and signaling those damaged DNA molecules very, very rapidly. So, we study those events that occur during that first recognition process. We look at how breaks are repaired.

We do this using biochemistry, which means that we make these enzymes, purify them and look at what the enzymes are doing. You can control everything in the reaction very carefully, which lets you make conclusions about what exactly those enzymes are doing.

DT: I know you are funded by the Cancer Prevention Institute of Texas. How does you work fit into the field of cancer research?
Paull: We’re funded by cancer research organizations because there’s an obvious relation to cancer, although we’re not doing things like testing drugs. We’re not trying out new cancer therapies. We’re at the basic research level trying to understand why loss of certain genes results in cancer, and what the enzymes encoded by those genes normally do.

DT: I read you do research on an enzyme called ATM, which plays a role in tumor growth. What is the importance of ATM?
Paull: [ATM] is also occasionally found to be lost or mutated in spontaneous tumors in normal people. There’s been a lot of sequencing of cancer genomes recently, now that sequencing DNA is getting to be so inexpensive. Cancer is this whole progression of events — basically changes in the genome — that lead to a cell having the ability to grow without normal control. Normally, our cells have redundant layers of growth control, so there are many things that have to be disabled before a cell can get to that point. ATM is one of those things. It’s found to be gone or mutated in a certain percentage of tumors. In some cancer types, it’s gone in 50 percent of cases; in others it might be a rare event.

DT: Is the kind of research you do going to help doctors cater their treatments to patients depending on which kind of tumor they have?
Paull: Personalized cancer treatment is something we talk a lot about. It’s the idea that someday in the future you’re going to go in with a cancer diagnosis and someone will be able tell you, “In comparison with your normal genome you have these thousand changes that have occurred in your tumor.” I don’t think we’re that far from getting there. That’s mainly a cost issue at this point. The problem is, once you get this information, what does that mean? Maybe, out of those thousand mutations, there are one or two that are absolutely known to cause your type of cancer. But, in most cases, you find these mutations, and you don’t know what those things do. What do you do with the information? Figuring that out it is going to take a really long time.

DT: Right now, what’s the most advanced cancer treatment in terms of personalizing care?
Paull: Well, it’s been done very successfully with certain types of breast cancer. There’s a particular receptor that’s on certain breast cancers and not others, which they can pretty easily test for now. If you have that receptor, you can receive a treatment that is specifically for that tumor type and avoid going through all the horrible chemotherapy that just generally kills everything growing in your body. This [treatment] has been extremely successful. The toxicity is much less and there’s a huge success rate. So, that kind of thing is what everyone wants, but it takes a long time to get even one of those successes. 

Printed on Wednesday, May 2, 2012 as: UT professor speaks about her cell damage, cancer research