Three Texas A&M University scientists are joining colleagues across the Lone Star State in celebrating the recent lift of a nearly year-long moratorium involving the troubled Cancer Prevention and Research Institute of Texas (CPRIT) that left their individual grants along with nearly $3 million earmarked to support cancer-fighting research projects with Texas-sized potential in perpetual limbo.

Last December, Texas A&M chemists François Gabbaï and Daniel Romo and Texas A&M AgriLife biochemist Dorothy Shippen each were awarded $200,000 "High Impact/High Risk" grants from CPRIT. The trio of awards, initially approved along with 11 others at a December 5 oversight committee meeting as part of a broader slate of grants exceeding $85 million during the institute's final regular funding cycle of 2012, went unfunded in the wake of a Texas State Legislature-imposed grant-making moratorium and subsequent investigation into CPRIT amid agency-wide allegations of fraud and mismanagement.

That 10-month waiting period ended Nov. 1, when a new governing board for the $3 billion agency held its first meeting since February and began initiating contracts as one of the reconstituted body's first acts.

Prior to the hiatus, CPRIT had regularly awarded competitive grants on a peer-reviewed basis since 2009 in three broad areas: commercialization, research and prevention. "High Impact/High Risk" awards, one of nine sub-categories within research, are intended to help fund "short-term projects that are developmental or exploratory in nature targeting new avenues of cancer research that, if successful, will contribute to major new insights into the etiology, diagnosis, treatment, or prevention of cancers."

Gabbaï's research seeks to deliver improved radiopharmaceuticals for Positron Emission Tomography (PET), an imaging technique used in medical diagnosis. Current methods rely on the use of the fluorine isotope F18 as a radiological tracer that essentially creates a global positioning system (GPS) which allows physicians and radiologists as well as researchers to follow a biological pathway in real-time by tracking the emitted gamma rays produced as the F18 decays. The integrity of the F18-radiopharmaceuticals can be affected by water, a substance found in abundance within the human body. Because F18 also has a high affinity for boron, Gabbaï plans to use boron-based chemistry to "build a better F18 mousetrap" -- in this case a molecule that resists F18 release in aqueous environments, thereby buying precious tracking time while also improving signal strength and, in turn, overall diagnosis and treatment.

"By eliminating technological obstacles that currently hamper the field of PET cancer imaging, we expect that this research project will have a transformative effect on cancer diagnosis and patient management," Gabbaï said.

Romo's research involves a new approach to cancer chemotherapy focused on inhibiting protein synthesis -- specifically, "pro-survival" proteins that are produced as a unique defense mechanism by cancer cells in certain types of cancer, including leukemia and, in particular, chronic lymphocytic leukemia (CLL). Although these proteins are essential to the cancer cell's ability to live and multiply, Romo says they degrade rapidly. His goal is to reduce the concentration of these pro-survival proteins just enough using a potent protein synthesis inhibitor -- a simplified version of pateamine A, a compound derived from a marine sponge with which Romo has worked extensively during his natural-products-based career -- to "tip the scale" and force these cancerous cells to undergo apoptosis, or programmed cell death. He is working in collaboration with Prof. Bill Plunkett at MD Anderson, who has already demonstrated efficacy with CLL cells taken from MD Anderson cancer patients.

"This has the potential to be a very directed approach to killing cancer cells," Romo said. "Importantly, this 'pro-survival' protein defense mechanism may turn out to be a more common feature in other cancers. We are excited to be able to start studying this approach to cancer chemotherapy, which could impact many people's lives."

Shippen, professor of biochemistry and biophysics in the College of Agriculture and Life Sciences, studies mechanisms that promote chromosome stability. A key player in this process is the enzyme telomerase, which continually synthesizes telomere repeats on chromosome ends. She says that while telomerase activity is necessary to promote cell proliferation, mis-regulation of the enzyme can have catastrophic consequences, including lethal genetic loss. Cancer cells are characterized by massive genome rearrangements -- a setting in which telomerase activity is unrestrained.

Shippen and her collaborators recently discovered that the flowering plant Arabidopsis restricts telomerase activity in response to DNA damage by increasing the abundance of a novel inhibitory RNA molecule. Working with co-principal investigator Prof. Robin Fuchs-Young in the Texas A&M Health Science Center, Shippen now will test the hypothesis that a similar RNA-mediated protective mechanism operates in normal human breast cells, and that loss of this response contributes to cancer development.

"This work will shed light on mechanisms that safeguard chromosome integrity and how they can be subverted during carcinogenesis," Shippen said. "Moreover, newly discovered telomerase regulatory RNAs have the potential to serve as novel biomarkers and targets for breast cancer prevention and treatment strategies."

To be eligible to receive CPRIT funds, applicants must be Texas-based entities, including public or private institutions of higher education, academic health institutions, universities, government organizations, non-governmental organizations, other public or private companies, or individuals residing in Texas.

To learn more about CPRIT, go to http://www.cprit.state.tx.us.

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Contact: Shana K. Hutchins, (979) 862-1237 or shutchins@science.tamu.edu

Hutchins Shana

  • Francois Gabbai

  • Daniel Romo

  • Dorothy Shippen

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