April 2, 2012
Elizabeth “Liz” Pempe and Weichen Xu, both graduate students in the Division of Chemical Biology and Medicinal Chemistry at the UNC Eshelman School of Pharmacy, have received Impact Awards from the Graduate School at the University of North Carolina at Chapel Hill.
The Impact Awards recognize outstanding graduate students whose research covers a variety of areas: education, the environment, economic development, health, public administration and more. Recipients present their research at the Graduate School’s Annual Graduate Student Recognition Celebration and receive a cash award for their accomplishments.
Elizabeth Pempe, “Using Structural Motifs to Improve Heparin Clearance”
Heparin is one of the oldest drugs currently in clinical use; it is essential for kidney dialysis and has uses related to stroke and thrombotic disorders, among other health concerns. Yet heparin creates its own health concerns: The compound varies widely, including the amount of time it takes to clear the body’s system. When used as an anticoagulant during surgery, ideally clearance would occur in a short period of time. For treatment of thrombotic diseases, clearance would occur over a longer term. Creating a controlled clearance rate for heparin would increase effectiveness and decrease the risk of the drug.
“Given the current heparin therapies and their drawbacks, my project aims to prepare heparin drugs to meet currently unfulfilled needs,” Pempe says.
Pempe is studying heparin structures for clues into the mechanism that controls the drug’s clearance. In 2008 the heparin clearance receptor stabilin-2 was identified. Now Pempe is collaborating with Edward Harris, PhD, the researcher who identified this receptor, on a component of her research project. While the receptor has been identified, the mechanism behind heparin clearance (how the structure binds to the receptor) has not. Pempe and postdoctoral associate Yongmei Xu formed ten differently patterned heparin compounds and studied how Harris’s stabilin-expressing cells reacted in the presence of each compound to learn more about possible clearance triggers.
She followed up on this research by investigating the minimum length of the compound necessary for it to bind to Stabilin receptors, and the next phase will advance to a rat model study. Her several research projects all center on one goal, she says.
“Ms. Pempe developed this research project by herself, and the project turns out to be a highly important topic,” says Jian Liu, PhD, Pempe’s dissertation adviser.
Weichen Xu, “Molecular Diagnostics of Prostate Cancer by Kinase Reporters and Capillary Electrophoresis”
According to government data, 7,679 men in North Carolina were diagnosed with prostate cancer in 2011. Prostate cancer is typically a slow-growing disease, which means that most patients will die with—and not from—this cancer. However, some patients will develop a deadly aggressive form. Research has not yet uncovered an effective way to distinguish between the two types of prostate cancer at the time of diagnosis. Being able to determine whether a man’s prostate cancer is slow-growing or aggressive could prevent unnecessary, costly, and potentially risky treatments.
The protein Src kinase regulates cell function and has been proven to affect progression of prostate cancer. Xu studied whether a relationship exists between this protein’s activity and prostate cancers of varying aggressiveness. She also wanted, ultimately, to measure Src activity in a way that could translate into a rapid patient screening test. She employed capillary electrophoresis to measure Src activity, a highly sensitive technique that allows for rapid sample handling and has proven effective with patient biopsies.
Using a series of prostate cell lines, Xu discovered that total Src activity decreases with increasing prostate cancer cell line aggressiveness. This was surprising, but further investigation indicated that aggressive cell lines also have less total Src content. Xu subsequently discovered that a direct correlation exists between prostate cancer aggressiveness and the fraction of Src that is active. In doing so, she found a potential biomarker for aggressive prostate cancer.
“We suspect that the development of multiple biomarkers will be helpful in providing an accurate diagnosis and prognosis. Our ultimate goal is to apply this technology in the evaluation of prostate cancer patient samples,” Xu says.
She is collaborating with UNC-Chapel Hill faculty members Nancy Allbritton, MD, PhD, and David Lawrence, PhD, to study other potential biomarkers. Lawrence is a Fred Eshelman Distinguished Professor and chair of the School’s Division of Chemical Biology and Medicinal Chemistry.
“If, as we anticipate, her technology proves useful in distinguishing between aggressive and nonaggressive prostate cancer, then many men of North Carolina will be spared unnecessary surgery, whereas others may be saved through aggressive therapeutic intervention,” says Lawrence, in whose laboratory Xu conducts her research.
The Impact Awards are privately funded through the generous support of the Graduate School’s Graduate Education Advancement Board. For information on other winners, visit http://gradschool.unc.edu/student/awards/impact/2012.html.
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