The Year in Research

Our School of Medicine research teams, in collaboration with scientists across campus and around the world, have continued their impressive efforts to make crucial discoveries in nearly every field in biomedical sciences."

Blossom Damania, PhD, Vice Dean for Research at the UNC School of Medicine

In fiscal year 2023, UNC School of Medicine researchers in clinical and basic sciences made enduring discoveries important for human health and the people of North Carolina, in collaborative alignment with the mission of UNC Health. The school increased its total research funding portfolio to $626 million through June 2023, a growth of nearly $3 million from fiscal year 2022. The UNC School of Medicine surpassed the $500 million milestone in fiscal year 2019.

Total research funding portfolio in 2023

“Our School of Medicine research teams, in collaboration with scientists across campus and around the world, have continued their impressive efforts to make crucial discoveries in nearly every field in biomedical sciences,” said Blossom Damania, PhD, Vice Dean for Research at the UNC School of Medicine, who was elected to the American Academy of Arts and Sciences in October 2022. “This is such an incredible place to work, with new faculty bringing fresh ideas and technological expertise to pursue discoveries like never before, and mid-career and veteran faculty continuing to break barriers in our understanding of human health and disease while dedicating much of their time to mentoring the next generation. I could not be prouder of what our scientists are achieving in both the basic science and clinical research realms.”

Research funding for the School of Medicine has grown steadily over the last several years, increasing by more than $164 million over the past five years since fiscal year 2018. The UNC School of Medicine accounts for more than half of all research funding at UNC-Chapel Hill, which surpassed the billion-dollar milestone in 2020.

Although the National Institutes of Health funds more than half of UNC School of Medicine, the school of medicine also receives research funding from the State of North Carolina, PCORI, the Department of Defense, the National Science Foundation, and many nonprofit organizations and private foundations.

The accomplishments of UNC School of Medicine researchers are too many to detail here, but you can find many more the UNC Health Marketing and Communications team covered at our newsroom: news.unchealthcare.org. You can even search by month or topic!

Below are several of the most noteworthy research stories from the fiscal year 2023 that our UNC Health team covered.

A Key Breast Cancer Discovery

Understanding why cancers respond or don’t to therapy is crucial for effective and personalized treatment. In HER2-positive breast cancer, the immune system is a key player in a person’s response to anti-HER2 drugs. Important cells in the body’s immune system include B-cells, which create antibodies that neutralize cancer cells and infections. Also, T-cells directly fight cancers and infections.

This past year, UNC Lineberger Comprehensive Cancer Center researchers found that measuring activation of immune-system B cells may be better than measuring either T-cell activation or the total number of immune cells in and around a tumor, leading to a better prediction of whether HER2-positive breast cancer responds to treatment. The findings, published in JAMA Oncology, may allow doctors to be more precise in choosing which drugs, and how many drugs, to use in treating HER2-positive breast cancer. Lisa Carey, MD, deputy director of clinical science and the L. Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, led this study.

Lisa Carey, MD

A Smarter Way to Treat Brain Tumors

Aggressive brain tumors are notoriously tough to treat. Many tumors are difficult to reach because they grow deep into the brain. Also, a protective capillary system surrounding the brain can weaken a drug’s ability to kill the tumor cells it’s meant to target. And the complexity of different brain tumor mutations can render some genetic analyses ineffective. These and other factors can make choosing a best course treatment difficult.

UNC Lineberger scientists have developed a tool called a “slice platform” that may help make those decisions easier. This process offers a unique way to keep tumor cells alive outside of a cancer patient. Researchers can simultaneously test up to a dozen different drugs to see which ones most effectively kill the live tumor cells. This highly complex process takes just four days in the UNC Lineberger lab of Shawn Hingtgen, PhD.

Slice technology has been previously used to successfully study stroke and neurodegenerative disease, and around 2016, researchers such as UNC Lineberger’s Al Baldwin, PhD, began exploring it to study cancer. But putting live patient tumor tissue onto the brain slices so they can grow is a novel idea, and the research team’s excitement about the possibilities is palpable.

A New Clinician’s Tool to Screen for Eating Disorders

Christina Peat, PhD

Christine Peat, PhD, director of the National Center of Excellence for Eating Disorders at UNC-Chapel Hill, led the creation of an asy-to-use, digital screening tool that is free and available to all primary care clinicians to help expand care for patients with eating disorders. The tool lets providers quickly and easily administer an evidence-based screener to patients. If an individual screens positive for a possible eating disorder, providers can use conversation guides and resources from the tool to speak to the individual about next steps to address the condition.

The challenge with eating disorders is that many individuals do not have obvious signs or symptoms..."

More than 28 million Americans will have an eating disorder in their lifetime and eating disorders lead to 10,200 deaths every year in the United States. Research shows that eating disorders are getting worse or have been exacerbated during the COVID-19 pandemic. Because early diagnosis and treatment leads to better outcomes for patients, there is an urgent need for a more comprehensive approach to identify and help people who have eating disorders.

“We know that primary care clinicians are well-versed in screening for various mental health conditions, and they feel comfortable in this role,” said Peat, associate professor of psychiatry. “The challenge with eating disorders is that many individuals do not have obvious signs or symptoms so these conditions can go undetected without routine screening. Our tool addresses that challenge by equipping clinicians with a tool that is brief, easy to use, and geared toward their scope of practice.”

Surprise Anticancer Properties of Common Lab Molecule

Experiments from the UNC School of Medicine lab of Nobel Prize-winning scientist Aziz Sancar, MD, PhD, show how a common molecular tool for DNA labeling in lab work also has anticancer properties worthy of further investigation, especially for brain cancers. The molecule is called EdU. And Sancar’s lab found that human cells recognize EdU as DNA damage, triggering a runaway process of DNA repair that is eventually fatal to affected cells, including cancer cells.

The discovery, published in the Proceedings of the National Academy of Sciences, points to the possibility of using EdU as the basis for a cancer treatment, given its toxicity and its selectivity for cells that divide fast.

“We want to stress that this is a basic but important scientific discovery,” said Sancar, the Sarah Graham Kenan Professor of Biochemistry and Biophysics. “The scientific community has much work ahead to figure out if EdU could actually become a weapon against cancer.”

Aziz Sancar, MD, PhD

A New Map of the Developing Cerebral Cortex

These results provide an important reference for exploring and understanding the dynamics of early brain development..."

What’s the undiscovered country of biology? Some say our genome. But it might be the brain. We still don’t know so much about the human brain. For the first time, this year, scientists at the UNC School of Medicine used high resolution MRI data to map the surface of the cerebral cortex of the young human brain with unprecedented resolution, revealing the development of key functional regions from two months before birth to two years after.

The new cortical development mapping, reported online in the Proceedings of the National Academy of Sciences, represents a valuable resource for further research on brain development and offers a powerful new approach to the study of brain-development conditions such as autism and schizophrenia.

“These results provide an important reference for exploring and understanding the dynamics of early brain development,” said study senior author Gang Li, PhD, associate professor of radiology at the UNC School of Medicine. The study’s first author was Ying Huang, a PhD candidate in Li’s laboratory.

A New Kind of TB Drug Delivery

In 2020, more than 1.5 million people around the world died of tuberculosis, marking the first time in more than a decade that annual TB deaths had increased and demonstrating the global need for better access to treatments. To address that problem, scientists at the UNC School of Medicine, the UNC Institute for Global Health and Infectious Diseases, and the International Center for the Advancement of Translational Science developed a long-acting injectable formulation of the anti-TB drug rifabutin.

Published in the journal Nature Communications, research in animal models showed the potential of delivering a TB drug with one injection that lasts at least four months, in lieu of the current standard treatment requiring constant adherence to a daily drug regimen.

The research was led by Carolina researchers Martina Kovarova, PhD, Miriam Braunstein, PhD, and J. Victor Garcia, PhD.

“We think our approach could dramatically change TB treatment,” said Kovarova, associate professor of medicine. “Affordable long-acting formulations with generic anti-TB drugs would help ease the burden of this disease on low-income communities around the world where better access to treatment is most needed.”

A Non-Psychedelic Compound with Anti-depressant Effect

These results provide an important reference for exploring and understanding the dynamics of early brain development..."

While illegal for recreational use, psychedelic drugs are showing great promise as treatments for severe depression and anxiety, as well as alcohol addiction and other conditions. Some advocates and scientists believe the actual psychedelic trip – hallucinations and profound emotional experiences– is what leads to long-lasting therapeutic effects. Other scientists speculate that if the ‘trip’ could be eliminated from such drugs, then only the therapeutic effects might remain.

Researchers at UNC-Chapel Hill, UC San Francisco, Yale, Duke, and Stanford have taken a major step toward answering that question.

Published in Nature, this research in animal models show it’s possible to create a compound that hits the same exact target that psychedelic drugs hit – the 5-HT2A serotonin receptors on the surface of specific neurons – but does not cause the same psychedelic effects when given to mice. The new compound triggers the same anti-depressant action that researchers have long observed in mice treated with SSRI drugs over the past two decades, with just two differences: the anti-depressant action of the new compound was immediate and long-lasting after just one dose.

“We were very surprised the compound had any anti-depressant activity similar to ketamine and psilocybin, both rapidly acting antidepressant psychedelic drugs,” said co-senior author Bryan L. Roth, MD, PhD, the Michael Hooker Distinguished Professor of Pharmacology at the UNC School of Medicine and director of the NIMH Psychoactive Drug Screening Program. “We were basically running a chemistry experiment to see if we could create a compound to activate 5-HT2A. Once we achieved that, we decided to run experiments in mice.”

Building Better Pain Medications

Also out of the Roth lab comes research led by former UNC graduate student Jeff DiBerto, PhD, who used cryoEM technology to solve the detailed structures of the entire family of opioid receptors bound to their naturally occurring string of amino acids in brain cells. The lab also conducted biochemical studies to better understand how drugs bind to brain cells.

This work, published in top journal Cell, provides a comprehensive structural framework that should help drug developers design safer drugs to relieve severe pain.

Former Roth lab graduate student Jeff DiBerto, PhD, led the pharmacological experiments to understand the detailed mechanism inside cells when drugs bind to neurons to relieve pain. The idea is to target only the bits of cells that lead to pain relief, while avoiding nasty side effects. DiBerto is now working for a company spun out of the Roth lab to take this research to the next level.

The Best of Diabetes Drugs

John Buse, MD, PhD

People with well-controlled diabetes generally have a high quality of life and have a much lower risk of disability and early death, and they generally respond well to changes in diet and exercise, though most people need medications to manage their blood glucose levels and avoid complications.

“There is general agreement among doctors that metformin, the most common first-line medication for treating type 2 diabetes, combined with diet and exercise is the best early approach in diabetes care,” said John Buse, MD, PhD, the Verne S. Caviness Distinguished Professor of Medicine. “However, most people with diabetes will require more than one medicine to control their condition over time.”

The nationwide GRADE study, with leadership and participation from UNC School of Medicine researchers, compared four different second-line therapies on the background of metformin and their ability to maintain blood glucose levels in a healthy range over time. The trial found that two of the treatments, glargine and liraglutide, worked better than the other drugs, sitagliptin and glimepiride, to maintain blood glucose levels.

Their results were published in a pair of papers in the New England Journal of Medicine. Sue Kirkman, MD, a professor of medicine in the division of endocrinology and metabolism, was a principal investigator on the study and co-chair of the outcomes adjudication committee.

Excellence in Autism Research

The National Institutes of Health awarded $100 million over the next five years to support nine Autism Centers of Excellence (ACEs), which lead multi-institutional research projects to understand and develop interventions for autism spectrum disorder (ASD).

Created in 2007, the ACE program is renewed every five years. The UNC-Chapel Hill ACE, led by Joe Piven, MD, director of the Carolina Institute for Developmental Disabilities, is the only one of the nine to have been funded for four consecutive grant cycles. Prior to the ACE program, UNC-Chapel Hill received a STAART (Studies to Advance Autism Research and Treatment) Center grant from the NIH in 2003.

With this new 5-year, $12-million ACE grant, the Infant Brain Imaging Study (IBIS) Network will examine brain and behavior development in a group of 400 children (300 of whom are at high familial likelihood of ASD). The children entered this study as infants, before the typical age of onset of ASD and are now entering adolescence, which is the time of onset for most adult psychiatric disorders. The researchers will continue documenting the trajectories of brain and behavior development, from infancy through adolescence, in those with ASD as well as those at high likelihood for ASD who develop other psychiatric conditions that are genetically related to ASD.

Funding awarded over the next five years for autism research

Joe Piven, MD

Focused Ultrasound for Parkinson’s

Vibhor Krishna, MD

Researchers at the UNC School of Medicine led a pivotal multicenter, double-blinded, randomized clinical trial to show that unilateral focused ultrasound ablation reduced dyskinesia and motor impairment in patients with Parkinson’s disease. UNC neurosurgeon Vibhor Krishna, MD, co-led the study, which was published in the New England Journal of Medicine.

Parkinson’s disease is a common neurological disorder characterized by the loss of dopamine neurons in the brain. Patients with Parkinson’s disease can be effectively treated with medications. However, some patients develop dyskinesia – involuntary movements – and motor impairment. At the same time, motor impairment is characterized by the return of debilitating Parkinsonian symptoms as medication effectiveness declines.

Patients who receive focused ultrasound treatment can go home the same day after surgery. This treatment was FDA-approved for patients with essential tremor in 2016, and now this pivotal trial has led to FDA-approval of focused ultrasound ablation to treat dyskinesia and motor impairment in Parkinson’ disease.

Scientists Make Stunning Chromosome Discovery

Once thought incapable of encoding proteins due to their simple monotonous repetitions of DNA, tiny telomeres at the tips of our chromosomes seem to hold a potent biological function that’s potentially relevant to our understanding of cancer and aging.

Reporting in the Proceedings of the National Academy of Science, UNC researchers Taghreed Al-Turki, PhD, and Jack Griffith, PhD, made the stunning discovery that telomeres contain genetic information to produce two small proteins, one of which they found is elevated in some human cancer cells, as well as cells from patients suffering from telomere-related defects.

“Based on our research, we think simple blood tests for these proteins could provide a valuable screen for certain cancers and other human diseases,” said Griffith, the Kenan Distinguished Professor of Microbiology and Immunology and member of the UNC Lineberger Comprehensive Cancer Center. “These tests also could provide a measure of ‘telomere health,’ because we know telomeres shorten with age.”

Griffith, who was featured nationally on Science Friday, has applied for a patent on a new blood test to help with cancer diagnostics.