Each spring, the UNC Graduate School announces its list of Impact Award recipients whose research contributes to the state of North Carolina in some way. When it comes to the UNC School of medicine winners, these contributions aim to improve health outcomes for our citizens.
This year, five of the 20 Impact Award winners are from five departments inside the UNC School of Medicine.
Maria Aleman, PhD, in the department of pathology, earned her impact award for her work on the importance of factor XIII in blood clotting. For years, scientists thought that red blood cells were simply trapped in a clot and had no active role in the clotting. Through experiments in the lab of Alisa Wolberg, PhD, Aleman found that factor XIII is activated inside red blood cells when they are trapped in a clot.
“Once factor XIII is activated, then a fibrin matrix is created,” Aleman said. “The matrix is like a net; it’s the major product of clotting. This network is keeping red blood cells in the clot.”
Aleman found that without factor XIII, the clot retracts, consolidates, and becomes physically smaller. “The clot squeezes and becomes a firmer mass and this is when red blood cells can be squeezed out,” Aleman said.
“This gives us insight into an approach to potentially develop a therapeutic,” she added. “You wouldn’t want to get rid of factor XIII altogether because that would cause bleeding, but if you could delay its activation and make the clot smaller, then this could be beneficial for long-term outcomes for patients with deep vein thrombosis, for instance.”
Kari Debbink, PhD, in the department of microbiology and immunology, studied norovirus, also known as the stomach flu, which affects hundreds of thousands of North Carolinians each year. In some ways, norovirus is like influenza in that different strains seem to dominate each year, making the creation of an effective vaccine more difficult.
Debbink created experimental assays that allowed her to find parts of norovirus particles that our natural antibodies bind to, thus helping us fight off the infection. These parts are called neutralizing epitopes, and they are important to understand for the creation of vaccines.
“We were able to find what we think are the major neutralizing epitopes for norovirus,” Debbink said. “So with this information we can start to design more targeted vaccines, which we don’t have at this point.”
The research will allow scientists to think of ways to design vaccines that can be easily reformulated each year as the virus changes.
Madisa Macon, PhD, in the department of toxicology, studied the manmade chemical perfluoro-octonoic acid, also known as PFOA. It’s primarily found in stain-resistant products and non-stick products, such as those used on frying pans. When such compounds break down, PFOA is released. It’s a known carcinogen and is now found in the environment – in house dust, food, water, clothing, and even breast milk.
Macon used a mouse model to study how PFOA altered the development of mammary glands. Her results suggest that PFOA altered the sex hormone signaling pathways. She discovered reduced side branching [KO1] of the glands. She also found that the epithelial ducts were thicker in PFOA-affected mice. All have previously been associated with an increased risk of breast cancer.
Macon's studies have already been used by two government agencies in their human health assessment of PFOA toxicity. Her research could be used by regulatory agencies in North Carolina and beyond in further assessment of the dangers of PFOA and regulation of products that contain it.
Agostina Santoro, a graduate student in the department of cell and molecular biology, studies the links between insulin receptors, obesity, and colorectal cancer. For many years, scientists have known that people who are obese face a greater risk of developing colorectal cancer.
Santoro created mouse models of obesity to study how they respond to radiation, which is known to damage DNA. What you’d want the cell to do when DNA is damaged is to trigger cell death, a process called apoptosis. But DNA damage can trigger cancer development
Santoro found that obese animals exposed to radiation had decreased cell death, high insulin levels, and an increased risk of cancer. These findings were consistent with human clinical data.
“The novel thing about our study was that we used animals that were genetically engineered,” Santoro said. “They either lacked insulin receptors in the intestine or they had an intact receptor.”
Santoro’s experiments showed that the insulin receptors played a role in whether cells died or became at risk of becoming cancer cells. High insulin levels, she found, played a role in carcinogenesis.
She also studied human biopsies to find that a variant of the human insulin receptor can induce cell proliferation and is involved in cancer. “This insulin receptor variant is increased in patients with precancerous polyps,” She said. “Again, this points to the insulin receptor as a factor.” The variant was more common in obese patients with high insulin levels.
Paul Sheeran, a graduate student in the department of biomedical engineering, focuses on creating better and cheaper imaging techniques to diagnose cancer in rural areas where access to hospitals and expensive, high-resolution imaging tools is limited.
Cancer remains the leading cause of death in North Carolina, and people in rural counties face a significantly greater risk of dying from cancer than do people in urban areas. Researchers think this is at least partly due to limited access to the best kinds of imaging used to diagnose tumors.
Ultrasound imaging is relatively inexpensive and portable, which is a key advantage for rural areas. But the contrast agents used to create an ultrasound image do not penetrate the tissue of tumors as effectively as contrast agents used in magnetic resonance imaging (MRI) or computed tomography (CT). This means that ultrasound images are not as clear or as helpful to doctors as are images from MRI or CT.
Sheeran’s research focuses on creating new, highly sensitive contrast particles for ultrasound that can overcome these limitations.
Specifically, Sheeran has worked to develop nanoparticles that can be manipulated by ultrasound energy and used to image and treat highly vascularized cancers.
A lot of cancer research in the past decade has focused on how fast-growing cancers recruit new blood networks rapidly, leaving gaps in blood vessel walls that don't exist in healthy tissue. By delivering carefully designed particles to the cancerous tissue through these ‘leaky’ vessels, Sheeran and his colleagues are hopeful that soon doctors will be able to image and attack tumors more effectively using ultrasound.
Check out the full list of UNC Graduate School Impact Award winners from across the sciences and humanities.