When Ying Xu examines images of a failing heart, the data in front of her become deeply personal.
She sees a heart that is enlarged and struggling to pump. She thinks not only about the patients represented by those images, but also about members of her own family who have experienced cardiovascular disease and hypertension.
“It really makes me more determined to work harder,” Xu said.
For Xu, a Ph.D. candidate in Pharmaceutical Sciences at the University of Houston College of Pharmacy (UHCOP), cardiovascular research is more than an academic pursuit. It is an opportunity to address a group of diseases she has witnessed throughout her life.
“On my father’s side of the family, cardiovascular disease and hypertension are very common, and witnessing their long-term impact has strongly shaped how I think about health and disease,” Xu said.
That personal connection, combined with her experiences as a first-generation college student, helped lead Xu to the laboratory of UHCOP Professor Bradley K. McConnell, Ph.D., FCVS, FAHA. There, she is investigating how disrupted molecular communication inside heart muscle cells may contribute to arrhythmia and heart failure.
The American Heart Association (AHA) recently awarded Xu a predoctoral fellowship to support her research into two proteins that may play important roles in the development of cardiac dysfunction.
Xu also has received recognition for presenting her findings to the scientific community. She earned first place among graduate student oral presenters at the 2025 UHCOP Department of Pharmacological and Pharmaceutical Sciences Symposium. She later received a Basic Cardiovascular Sciences New Investigator Travel Award to present her research, “Compartmentalized cAMP Dysregulation by the AKAP12-PDE8A Axis Drives Electrical Remodeling and Heart Failure,” at the AHA Basic Cardiovascular Sciences Scientific Sessions in Boston in July.
Decoding the Heart’s Signals
Xu studies cardiomyocytes, the specialized muscle cells responsible for the heart’s rhythmic contraction. These cells depend on a carefully coordinated network of molecular signals to ensure the heart contracts and relaxes properly.
One of those signals is cyclic adenosine monophosphate, or cAMP, which helps regulate cardiac contraction. Xu is examining how two proteins — A Kinase Anchoring Protein 12, known as AKAP12, and Phosphodiesterase 8A, or PDE8A — may disrupt that process.
AKAP12 normally acts as a scaffold or “information hub,” bringing proteins together so signals reach the right location at the proper time. However, AKAP12 levels increase in failing hearts, particularly during advanced disease.
Xu’s research explores whether excess AKAP12 recruits PDE8A, an enzyme that breaks down cAMP, and causes signals essential to healthy heart function to disappear too quickly. Beta-adrenergic receptors rely on cAMP signaling to help regulate how strongly and quickly the heart beats, particularly in response to stress or increased demand.
“My hypothesis is that AKAP12 and PDE8A form a dynamic axis downstream of the beta-adrenergic receptor,” Xu said. “What we’re trying to do is block this signaling and stop the heart from progressing into those diseases.”
Although PDE8A is found in relatively small amounts in the heart, Xu said its effect may be disproportionately powerful. Previous work in the laboratory found that PDE8A has a particularly strong ability to break down cAMP.
“Even though the amount is small, the function plays a big role,” Xu said.
Searching for Greater Precision
Treatments such as beta-blockers can improve survival and slow the progression of heart failure, but they do not fully restore normal cardiac function. Because beta-adrenergic receptors influence numerous pathways throughout the heart, broadly targeting them may affect many downstream signals.
Xu’s work is focused on a more narrowly defined molecular pathway.
“What makes PDE8 particularly different is that it works very precisely downstream of AKAP12,” Xu said. “Because it is more precise, it might bring fewer side effects and possibly even better effects. That is our hypothesis.”
Rather than affecting an entire signaling network, a treatment aimed specifically at the AKAP12-PDE8A axis could potentially interrupt harmful activity while preserving other functions the heart needs.
Through cell studies and advanced murine models, Xu is examining how this pathway affects calcium handling, electrical activity and cardiac contraction. She is now testing whether inhibiting PDE8A can protect against arrhythmia and heart failure.
Early findings are encouraging. Xu’s preliminary data suggest that PDE8A inhibition may improve contractile signaling and reduce the rate of arrhythmia associated with AKAP12 overexpression. Additional research will be necessary to determine the extent of that protective effect and whether the approach could ultimately contribute to a new therapy.
Keeping Patients in Mind
Even when her work centers on a single cell or a complex molecular pathway, Xu remains motivated by the people who could one day benefit from the results.
Behind every image, every measurement and every irregular heartbeat, she sees a patient, and sometimes, a member of her own family.