Two Johns Hopkins research teams received competitive translational funding awards totaling approximately $200,000 through the Louis B. Thalheimer Fund for Translational Research.
Established through a generous $5.4 million gift from businessman and philanthropist Louis B. Thalheimer, the award provides seed funding for vital proof-of-concept and validation studies of groundbreaking Johns Hopkins technologies with promising potential to impact human health and society. In late May, finalists presented their proposals to an external panel of independent investors and researchers, innovation executives, and venture investors.
Since its inception in 2016, the Thalheimer Fund has awarded over $2 million to more than 25 projects at Johns Hopkins, with grants ranging from $25,000 to $100,000. All recipients formally reported their inventions to JHTV. Last year’s winners included a new biosensor technology to identify drugs to treat cardiac arrhythmias, a scalable and cost-effective method to extract lithium from seawater for battery production, and a DNA-barcoded platform to select cell lines in biopharmaceutical manufacturing.
This year’s awardees further exemplify the outstanding spirit of innovation across departments at Johns Hopkins University. Read on to learn about the newly funded projects making strides from laboratory discoveries toward real-world applications.
Preclinical Feasibility Study for Gene Therapy-Powered Cardiac Pacing
Principal investigator:
Hee Cheol Cho, PhD
Associate Professor of Surgery, Pediatrics, Biomedical Engineering, and Anesthesia & Critical Care Medicine
Co-Director, Blalock Taussig Thomas Pediatric and Congenital Heart Center
The pitch: Transforming ordinary heart cells into pacemaker cells through gene therapy for a device-free, minimally invasive solution.
Electronic pacemakers are a vital lifeline for individuals with cardiac rhythm disorders, but their use comes with significant challenges—including repeated surgeries, infection risk, device malfunctions, and complications arising from lifelong hardware within the body. This is even more critical in pediatric populations, where patients may require multiple device replacements and face a lifetime of related morbidity.
Cho and his multidisciplinary team are developing an innovative, non-device-based alternative: a biological pacemaker created using gene therapy. Their approach utilizes lipid nanoparticle (LNP)-encapsulated modified messenger RNA (mRNA) to deliver TBX18, a cardiac transcription factor that can reprogram ordinary heart cells to function as pacemaker cells. Thus far, the team has established robust preclinical models to evaluate the feasibility and effectiveness of this therapy, demonstrating that biological pacing enables the heart to regulate its rhythm without reliance on mechanical devices.
The team plans to use the Thalheimer funding to optimize gene-therapy delivery technologies, collaborating with clinical experts to refine their approach for real-world patient and clinician needs. If successful, the solution could offer a less invasive, longer-lasting, and safer alternative to implanted pacemakers.
Inhibiting Nonsense-Mediated Decay Generates Neoantigens That Stimulate a Potent Anti-Cancer Immune Response
Principal investigator:
Kenneth Kinzler, PhD
The Barry Family Professor of Oncology
Professor of Genetic Medicine
Director, Ludwig Center at Johns Hopkins University
The pitch: Making cancer more visible to the immune system for better treatment outcomes and enhancement of cancer immunotherapy.
For many patients with cancer, immunotherapy has offered new hope, but it remains ineffective for many cases, as tumors are often able to hide from the body’s natural defenses. This challenge is particularly pronounced in cancers that evade recognition by not producing enough markers—or “neoantigens”—that alert the immune system to their presence.
Kinzler and his team are developing a groundbreaking approach to overcome this problem by making tumor cells more visible to the immune system. Their strategy targets a quality-control process inside cells called nonsense-mediated mRNA decay (NMD), which normally prevents faulty genetic messages from producing abnormal proteins. By temporarily blocking this process with new small-molecule drugs, the team can increase the number of unique neoantigens on cancer cells, helping the immune system detect and attack tumors that would otherwise go unnoticed.
Kinzler said, “Translating a discovery from an academic lab to real-world applications, particularly for therapeutics, is a complex and challenging process. JHTV and The Thalheimer Fund have been instrumental in providing critical guidance and funding to bridge this gap. The insights from their advisors have proven nearly as valuable as the financial support, empowering us to take meaningful steps forward on our journey.”
With support from the Thalheimer Fund, the team will focus on designing and testing improved NMD-inhibiting compounds, ensuring both safety and effectiveness in early studies. Their goal is to optimize this innovative treatment so it can eventually move toward clinical trials and offer a promising new option for patients whose cancers currently resist immunotherapy. If successful, this therapy could transform how doctors harness the immune system to fight cancer, opening the door to more personalized and effective treatments.