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NIH Grant Funds Cancer Research at UT

Published: June 22, 2009
While some college students spend the summer worshipping the sun, UT senior Mark C. Howell is spending his summer in a lab working on cancer research for a group called SUNSHADES.

SUNSHADES is made up of cancer researchers from Penn State College of Medicine and The University of Tampa, including UT assistant professor of chemistry Dr. Michael Carastro. The research group received a three-year, $150,000 grant from the National Institutes of Health (NIH) and the National Cancer Institute (NCI) last fall to study molecular defects in the vitamin D receptor (VDR), which can increase the risk of cancer. So far Carastro has had two students working for him on the project.

Vitamin D may play a role in several cancers and other chronic conditions, especially those with a higher incidence in African American populations. Most African Americans have a particular mutation in the VDR gene, called M1T, at a much higher frequency than those with European lineage. The higher frequency of the mutation is associated with an increased risk for colon, breast and prostate cancer, and lower survival rates.

“The difference is, in half of Caucasians and most African-Americans, the VDR protein is shorter,” Carastro says.

Normally, the vitamin D goes into cells and binds with the VDR, and it turns genes on and off. But if the VDR gene has the M1T mutation and the shorter version of the VDR protein is produced, it’s like a recording that starts 30 seconds into a song. The first part is missing and the VDR can’t signal properly when it binds to vitamin D.

Last fall Lisa Ladany ’08 spent a semester working on making the DNA expression constructs to test by using an experimental mutagenesis technique to create VDR genes with multiple combinations of mutations.

“It’s like writing a play,” Carastro says. “We were getting all the players together and blocking it out.”

Now that they have the cast of characters down, Howell is injecting these DNA constructs with the gene mutation into human lung cancer cells from a 41-year-old male patient who had terminal lung cancer. Then he adds a grow medium containing bovine calf serum, which helps grow the cells.

Howell will use Western analyses to see how the variants of the VDR gene are being affected by comparing the interaction of long and short VDRs in living human cells.

Through this research, Carastro hopes to determine how the defective VDR promotes cancer and create a plan to treat the cancer. If the vitamin D pathway is targeted, researchers may be able to improve chemotherapy treatment and develop strategies to reduce the occurrence and severity of hormonal-related cancer.

By using gene therapy, doctors could implant DNA intravenously, which could produce a longer VDR protein.

Carastro hopes that the research will result in other grants from the NIH and NCI, like Academic Research Enhancement Award (AREA) grants, which help fund research projects involving undergraduate students at small, non-PhD granting institutions.

“With grants like the AREA grants, we could have everything we need to do a large cancer research project right here at UT.”