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
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
“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.”