The Dr. Ralph and Marian Falk Medical Research Trust provides staged funding through their Catalyst and Transformational Award Programs that supports high-risk, high-reward projects that address critical scientific and therapeutic roadblocks. If successful, these projects will have high impact outcomes that open new avenues for treating, curing, and improving the lives of individuals suffering from disease. Projects must be responsive to the following areas of research focus: identification of biological markers or disease activity and progression, identification of targets for therapeutic interventions, and development of therapeutic agents that will disrupt, arrest, or prevent the disease process.
Learn about the 14 outstanding researchers who will receive research funding that has the potential to open new avenues for treating, curing, and improving the lives of individuals suffering from disease.
Awardee information: Catalyst Award
Moitrayee Bhattacharyya, PhD
INSTITUTE:
Yale University
Rational Design of Kinetoneurins to Uncouple TrkA Neurotrophic and Nociceptive Signaling
The project aims to uncover if it is possible to separate the pain-causing and nerve-protecting functions of the TrkA:NGF signaling pathway, to treat chronic pain in some patients and protect against neurodegeneration or combat nerve injury in others. This matters because achieving selectivity in TrkA:NGF signaling could deliver a powerful non-opioid pain medicine and the first nerve-protective and nerve-regenerative therapy for neurodegenerative diseases and nerve injuries, addressing two of the largest unmet needs in medicine today. By using the molecular blueprint of a rare variant of human NGF found in people who feel little or no pain, NGFpainless, the team will engineer and test a new class of drugs, kinetoneurins, which are designed to achieve two goals: either to block pain without harming nerves or to protect and regenerate nerves without triggering pain.
Kevin Black, MD & Jan Kubanek, PhD
INSTITUTE:
Washington University in St. Louis
Low-Intensity Focused Ultrasound in Tourette Syndrome: Within-Subject, Multi-Target Pilot RCT
The project aims to provide better treatment for the unwanted movements or sounds called tics caused by Tourette syndrome by using non-invasive brain stimulation with low-intensity focused ultrasound (LIFU). This research matters because many people with Tourette syndrome do not receive sufficient relief from current treatments, and progress depends on obtaining a clearer understanding of where to intervene in the brain and in which patients. The team will provide the first test of this non-surgical brain stimulation treatment in adults with Tourette syndrome, comparing several likely brain targets to determine which are most likely to reduce tic symptoms. These results will be essential for designing any future, larger study of LIFU for Tourette syndrome.
June Goto, PhD & Francesco Mangano, DO
INSTITUTE:
Cincinnati Children’s Hospital Medical Center
Development of AAV5-rapaCasp9: A Novel Gene Therapy for Minimally Invasive Choroid Plexus Ablation in Pediatric Hydrocephalus
The project addresses the question of whether pediatric hydrocephalus, a condition in which excess fluid builds up in the brain, can be safely and effectively treated with a one-time therapy that reduces the brain’s fluid production instead of relying on repeated surgeries. This matters because current treatments often fail and require many surgeries, placing a heavy physical, emotional, and financial burden on children and their families. The investigative team will answer this by testing a new gene-based therapy in two large animal models to measure how well it reduces fluid buildup in the brain and whether it is safe for future use in patients.
Stacey Halum, MD, FACS and Sherry Voytik-Harbin, PhD
INSTITUTE:
Indiana University
Mechanobiological Scaffold and Neuromuscular Signaling to Restore Structure and Function Following Volumetric Muscle Loss
The project addresses the question of whether a clinically deployable restorative scaffold can restore functional skeletal muscle after large-volume muscle loss, and if localized delivery of neuromuscular signaling factors can further improve nerve integration and muscle function during healing. This question matters because no clinically available treatment reliably restores skeletal muscle structure and function after major muscle loss, which can leave patients with persistent weakness, impaired movement, and long-term disability. The question will be addressed through integrated biomaterial engineering, scaffold characterization, localized neuromuscular signaling studies, and preclinical animal models that evaluate muscle regeneration, nerve integration, and functional restoration following volumetric muscle loss.
Scott Harper, PhD
INSTITUTE:
The Research Institute at Nationwide Children’s Hospital
AAV Capsid Engineering Targeting Schwann Cells of the Peripheral Nervous System
This project aims to improve gene delivery tools to safely and effectively target Schwann cells in peripheral nerves, with the ultimate goal of treating Schwann cell disorders of the peripheral nervous system. This matters because the current AAV-based gene therapies used to deliver gene therapies to Schwann cells are inefficient, and developing next-generation AAV vectors could improve delivery to more Schwann cells, enable lower doses and make treatments more effective and safer for peripheral neuropathies. To do this, the investigative team will create new gene delivery tools and test them in living models to identify those that most effectively reach Schwann cells in peripheral nerves.
Jan Kitajewski, PhD
INSTITUTE:
University of Illinois
Engineering Tumor Vasculature to Promote Immune Infiltration: Notch Peptibody-Driven Induction of Tumor-Associated High Endothelial Venules in Triple Negative Breast Cancer
The project aims to improve breast cancer treatments by inducing blood vessels to form specialized structures called high endothelial venules (HEVs), which act to facilitate immune cell infiltration into the tumor, promoting anti-tumor immune attack and suppressing breast cancer growth. Breast cancer generally shows low levels of immune cell infiltration, and increasing the number of infiltrating immune cells could dramatically increase the effectiveness of existing immune-activating (ICB) therapies, improving breast cancer outcomes and saving patient lives. The investigative team will test whether combining ICB therapy with two newly developed antibody-like proteins synergistically reduces tumor growth, induces HEV formation, and increases immune cell attack in mouse models of breast cancer and determine which breast cancer patients might benefit from these treatments.
Richard Lang, PhD
INSTITUTE:
Cincinnati Children’s Hospital Medical Center
Spectral Lighting for the Prevention of Myopia
This work asks whether redesigned indoor lighting can prevent myopia, commonly known as nearsightedness, before it starts, thereby reducing a global disease burden projected to affect 4.8 billion people by 2050, including 18.5 million people who will be blind. This question matters because myopia is extremely common, compromises daily visual function, burdens healthcare systems, and can progress to severe disease that causes permanent vision loss. To answer this question, the team will build a practical Spectral Lighting system, verify that it delivers the relevant wavelengths in real daycare rooms, test it in an established animal model of myopia, and install it in daycare centers to prepare for a future prevention study in children.
Wexin Tang, PhD
INSTITUTE:
University of Chicago
Context-Specific Genome-Editing Strategies for Monogenic Primary Immunodeficiencies
The project aims to address whether precise gene editing can provide curative treatments for inherited immune disorders. This research matters because it could provide a safe, curative treatment for children with inherited immune disorders who currently have few or no curative treatment options. To answer this question, the research team will develop precise gene-editing tools to repair disease-causing DNA changes and determine whether corrected patient stem cells can be used for safe, curative autologous transplantation.
Dereck Wainwright, PhD
INSTITUTE:
Loyola University of Chicago
Antisense Oligonucleotide Therapy for Patients With Glioblastoma
The project will address whether neutralizing immunosuppressive human indoleamine 2,3 dioxygenase 1 (IDO; IDO1) with therapeutic anti-sense oligonucleotides (ASOs) will re-enable the immune system to eradicate human glioblastoma. This problem is significant since IDO potently inhibits the anti-glioblastoma immune response, is present at high levels in human patient-resected glioblastoma, and glioblastoma is incurable. Addressing whether human IDO-targeting ASOs lead to immune system-mediated destruction of human glioblastoma in preclinical models will generate the necessary rationale for translating these novel therapeutics into a near-future clinical trial for human patients with glioblastoma.
Charles Williams, PhD
INSTITUTE:
Michigan State University
Optimization of Novel GPR68 Antagonists for Glioblastoma: A First-in-Class Chemocentric Approach to Overcoming Therapeutic Resistance
The project aims to determine whether blocking a specific acid-sensing switch on the surface of brain cancer cells can bypass treatment resistance and force deadly tumors to undergo a highly visible, immune-activating cell death. This matters because glioblastoma outcomes have not improved in over twenty years, and finding a way to exploit the tumor’s own acidity could yield a highly selective, first-in-class therapy that effectively destroys tumor tissue while sparing the healthy brain. The investigative team will synthesize optimized drug-like molecules that penetrate the brain, test their therapeutic power in patient-derived animal models, and detail the internal cellular pathways that dictate tumor destruction.
Awardee information: Transformational Award
Milan Chheda, MD
INSTITUTE:
Washington University in St. Louis
Safety and Feasibility of Genetically Engineered Zika Virus for Patients With High Grade Glioma
This work asks whether a genetically engineered Zika virus can be safely used to treat patients with high-grade glioma and ignite an immune response in the tumor. This question matters because high-grade gliomas remain uniformly lethal despite current therapies, largely due to treatment-resistant stem-like cells and an immunosuppressive tumor microenvironment. The project addresses this question through a first-in-human intratumoral Δ10 3′-UTR ZIKV dose-escalation trial with deep correlative tissue and blood profiling, paired with mechanistic mouse studies of next-generation ZIKV strains.
Amanda Garner, PhD
INSTITUTE:
University of Michigan
Development of AR-V7-Selective Modulators for Drug-Resistant Prostate Cancer
This project seeks to target androgen receptor splice variant 7 (AR-V7) for the treatment of drug-resistant prostate cancer. This question matters because expression of AR-V7 has been linked to the development of advanced prostate cancers, metastatic disease progression, and therapy resistance in prostate cancers, yet remains a not-yet-drugged and difficult therapeutic target. Through the Catalyst Award, the team identified promising AR-V7-selective inhibitors that will be further developed and tested in mouse models of prostate cancer to support clinical advancement.
Saad Kenderian, MD
INSTITUTE:
Mayo Clinic
CD19-Targeted Chimeric Antigen Receptor-Engineered Mesenchymal Precursor Cells (CAR-MPC19) in Lupus Nephritis (LN)
This project asks whether engineered allogeneic cell therapies answer an unmet clinical need, offer durable disease control, and prevent organ damage with minimal toxicities in autoimmune diseases such as systemic lupus erythematosus (SLE) and accompanying lupus nephritis (LN). SLE is a debilitating chronic autoimmune disease, is increasingly prevalent, is insufficiently treated by current therapies, and has no known cure to date. LN, which is a common and severe effect of SLE, can result in end-stage kidney failure. The investigative team has shown that chimeric antigen receptor (CAR)-engineered mesenchymal stromal cells (MSCs) show enhanced therapeutic effects compared to unmodified MSCs in mouse models of SLE and an established academic-industry partnership will take these CAR-MSCs to a Good Manufacturing Practice (GMP)-grade, translation-ready product to treat LN in patients with refractory SLE.
Francis McCormack, MD
INSTITUTE:
University of Cincinnati
A Biodegradable Particle for Pleurodesis
The project aims to develop a new approach to pleurodesis, a procedure which permanently seals the space between the lung and inside of the chest wall to prevent accumulation of air or fluid. The question the work will answer is whether hydroxyapatite pleurodesis is safer and more effective than talc pleurodesis. This question matters because talc pleurodesis is associated with exposure to lead, acute lung injury, chronic inflammation and pain, and surgical complications with subsequent thoracic procedures. To answer this question, the team will test efficacy and safety of this novel pleurodesis approach in small and large animal species and in clinical trials that will follow.