Cancer Research Leads to Possible Lyme Vaccine

As part of her research into breast cancer, University of Rhode Island scientist Roberta King has for years been studying the role of an enzyme in regulating estrogen activity.

As part of her research into breast cancer, University of Rhode Island scientist Roberta King has for years been studying the role of an enzyme in regulating estrogen activity.

King is specifically interested a type of enzyme, called sulfotransferases, which contribute to balancing

and regulating numerous biologically active compounds such as estrogen and dopamine.

Now the associate professor of biomedical sciences in the College of Pharmacy is targeting dopamine

sulfotransferase

and its potential role in the transmission of the bacteria that causes Lyme disease. In a partnership with Thomas Mather, professor of entomology and director of the URI Center for Vector-Borne Diseases, King and her research team are looking at how tick dopamine

sulfotransferase

affects tick salivation and ultimately the feeding process that leads to Lyme disease and other tick-borne diseases.

“In the lab, we have shown that the tick

sulfotransferase

controls dopamine activity. Because others have shown that dopamine controls tick salivation, we expect that manipulating the

sulfotransferase

may turn off salivation, which in turn would prevent ticks from feeding,” King said. “If we can prevent ticks from feeding, then we can

stop them from transmitting diseases.”

King said the research findings of her team will be printed in an upcoming edition of the American Chemical Society journal, ACS Chemical Biology.

King said she and Mather have been working together since 2006 when he approached her about targeting molecular pathways and mechanisms that lead to Lyme disease and other illnesses caused by ticks. Mather has been researching vaccines against Lyme disease for more than a decade.

“Tom’s team, which

has included Sivakamasundari Pichu, a former post-doctoral fellow, and Dr. Jose Ribeiro from the National Institutes of Health in Rockville, Md., identified tick genes that looked like

sulfotransferase

and that the gene expression level changed from before a tick fed to after a tick fed,” King said. “He keyed in on that action because it should be important biologically. Organisms don’t waste energy changing things unless they benefit from the change. We wanted to discover the purpose

of the gene and to see if the protein it produced could be targeted for a vaccine or drug.”

“As the research progressed, I was convinced that the

sulfotransferase

was controlling something important in the tick, just as estrogen

sulfotransferase

controls something important in breast cancer development. After three years of research, we’ve got a good understanding of what the enzyme does for ticks and why the gene levels change before and after feeding.”

She said deer ticks need to blood feed for longer than 24 hours to transmit disease.

“We don’t have to stop the initial bite, as much as we need to shorten the feeding process,” King said. “With these long-feeding ticks (they typically feed for 3 or more days), if we shorten the attachment time by interrupting salivation, then we may have an effective way to stop transmission of Lyme disease. We found that tick

sulfotransferase

turns off dopamine, which should turn off

salivation, and in turn prevent feeding. The tick then would drop off the person and/or die.”

Since King and her team have found that tick

sulfotransferase

is potentially a key to regulating salivation in lab tests with tick tissue, they are now proceeding with tests on live ticks in Mather’s lab.

King said they were initially looking at two options for attacking Lyme disease–a vaccine, which would target the

sulfotransferase

in the tick saliva, or a drug,

which would be absorbed into the tick. Mather’s research focus is on anti-tick vaccine development, “but it also may be possible to target the tick

sulfotransferase

using a topical drug,” King said.

King said a cream or lotion could be developed that people could apply to prevent ticks from feeding.

“This is a very exciting collaboration,” she said. “And while I have done much of my work studying human metabolic changes in relation to cancer to prevent illness,

through this collaboration I am looking at similar metabolic changes in ticks to also prevent human illness.”

Emine Bihter Yalcin, who graduated with her master’s degree in 2009 and is pursuing her doctoral degree with

King,

wrote her master’s thesis on the research, which became the basis of the scholarly article. Hubert Stangl, a former intern from Germany in the College of Pharmacy, was also a member of King’s team.

University of Rhode Island professor of biochemical

sciences Robert King has been conducting research with enzymes called sulfotramsferase, finding evidence that might be able to help prevent lyme disease.

King said URI professor of entomology and plant sciences Thomas Mather has studied ticks and with his findings made the connection between sulfotransferase and ticks.

“We have a possibility of a process but we haven’t proven that it works,” she said. King said they have proved that dopamine signals, produced by a neural transmitter, can

be turned off which is important for stopping the spread of lyme disease.

“Several years ago another lab group showed if you expose the live [ticks] to dopamine they will salivate,” King said. “Our idea is that if we can alter the sulfotransferase, which can probably turn off the dopamine ‘transignal,’ we expect that if we do turn it off it will prevent [ticks] from salivating, which will prevent them from passing on the disease.”

King is now working on proving that

sulfotransferase can turn off the dopamine signal. She said that the experiments are a lot about “connecting several dots” and figuring out how one thing relates to another.

According to a URI press release, King is looking at two ways to prevent Lyme disease, “a vaccine which would target the sulfotransferase in the tick saliva, or a drug, which would be absorbed into the tick.”

The experiment has been funded by university grants.  “But now that we’ve published the [research],” King said,

“we’ll be able to compete for outside grants.”

The first research paper has been published in the scientific journal ACS (American Chemical Society) Chemical Biology. It was published online in November and will come out in print in the journal in March.

King said she will continue her research with sulfotransferase to see if it can help cure other diseases. In the past she has experimented to find the cure for breast cancer, but has since moved on to other diseases like diabetes and

obesity in addition to her Lyme disease research.

“My work with sulfotransferase can be applied to many diseases because sulfotransferase can be applied to many things,” King said.

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