cancer treatment

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

Professor Chad A. Mirkin, director of the International Institute for Nanotechnology, speaks to a group of students and faculty Wednesday about the future of the science and the potential of chemical engineering.

Photo Credit: Lawrence Peart | Daily Texan Staff

Packaging the building blocks of DNA into microscopic nanostructures capable of being applied as a skin cream may be the future of cancer treatment, according to one nanotechnology pioneer speaking on Wednesday.

Chad Mirkin, director of the International Institute for Nanotechnology at Northwestern University, talked about the groundbreaking potential of chemically engineering nucleic acids and constructing DNA arranged in a spiky, spherical nanostructure that utilizes normal cellular processes to attack the genetic component of cancer cells.

Mirkin is researching therapeutic application for nanostructures ranging from one to 100 nanometers in length, about one-millionth of an inch.

“Right now, we have a disease like glioblastoma [most common form of brain tumor] that is basically a death sentence,” Mirkin said. “If we could create chemical constructs that could be delivered systemically to increase the lifespan of a patient from one year to five years, that would be unbelievable. To cure would be spectacular.”

The technology has successfully interrupted the growth of cancer in more than 50 types of cells and tissues, such as liver and nerve cells. Crucially, cancerous cell bodies that resist treatment are permitting the nanostructures to enter the cell for the first time — essential in delivering medicine to cancer sites effectively.

Mirkin said trials treating brain tumors in mice are already showing promising results.

“Gene regulation has the promise of treating and curing almost every disease out there that has a genetic basis, that’s the tantalizing and exciting prospect of it,” he said.

He said he was honored to discuss his research at UT.

“The Center for Nano- and Molecular Science is an incredible place,” Mirkin said.

“[UT] has a very passionate group of scientists and engineers who share a love of
scientific curiosity.”

Biomedical engineering graduate student Brandon Slaughter said he wrote to Mirkin in fall 2010 inviting him to speak at UT. He was initially rebuffed but persisted in proposing dates well into the future.

“It’s incredible,” he said. “We didn’t expect to get Professor Mirkin to come here, especially at a student-invited seminar. We discussed a few research opportunities this morning, so there may be something going forward,”
Chemical engineering graduate student William Liechty said Mirkin has the rare gift of being able to take lab technologies and translate them into com-mercial technologies.

“He did a great job covering a number of academic fields and tying it together in terms of controlling molecular architecture to do a number of neat things, such as diagnostic and therapeutic applications,” Liechty said. “Taking scientific discoveries and making them useful technologies is inspirational.”

News Briefly

UT faculty recently earned three grants worth $4.7 million from the Cancer Prevention and Research Institute of Texas to improve understanding of cancer treatment options.

UT’s Texas Institute for Drug and Diagnostic Development earned a $2.4 million grant. Kevin Dalby, associate professor of medicinal chemistry and co-director of the drug-development institute, said the state of Texas is going to spend $3 billion on cancer research over 10 years.

“This grant money will be used for screening for potential drugs,” Dalby said. “In collaboration with other universities, we have a combined program where we’re doing different things, but the ultimate aim is to find drugs that can cure cancer.”

The cancer institute also awarded Tanya Paull, a professor in molecular genetics and microbiology, a separate $1 million grant for her research.

“We’re doing research on the mechanisms of double-strand break repair, which is a form of DNA repair that is in all human cells. We’re trying to understand how that process takes place,” Paull said.

She said DNA damage and how cells deal with that damage is important in terms of whether conditions result in cancer.

Maria Person, director of the Protein and Metabolite Analysis Facility at the Institute for Cellular and Molecular Biology and the College of Pharmacy, got a $1.3 million grant to purchase mass-spectrometry equipment to examine molecular DNA damage.