The inaugural AACR-Ocular Melanoma Foundation Miriam Counts Innovation and Discovery Grants is a new grant mechanism that seeks to stimulate creative approaches to translate basic research into new treatment options for ocular/uveal melanoma.

2025 Grantees

Scientific Statement of Research

SF3B1 mutations occur in 15–20% of uveal melanomas and drive highly recurrent, nonrandom RNA missplicing events in mutant cells. Dr. Dalton and his research group have developed a nucleic acid therapeutic strategy that exploits mutant SF3B1 missplicing to express an attenuated diphtheria toxin A (aDTA) that poisons mutant cells – an approach called Mutation‑Induced Synthetic Intron Lethality (MISIL). MISIL has shown selective killing of SF3B1‑mutant uveal melanoma cells in vitro when delivered by AAV2, sparing isogenic wild type cells. He will evaluate MISIL in vivo, using AAV to treat mice xenografted with human uveal melanoma by intratumoral and systemic delivery. In parallel, he will test enhancements to MISIL through additional SF3B1‑specific cryptic introns and alternative viral vectors. This work seeks to establish a proof‑of‑concept for exploiting mutant splicing through viral delivery of nucleic acids in uveal melanoma, laying the groundwork for expanded studies in additional models, primary patient samples, and possible future clinical translation.

Biography

Dr. Dalton earned his medical and doctoral degrees from Emory University and trained in Internal Medicine and Medical Oncology at the Johns Hopkins University School of Medicine. Currently, he is an Assistant Professor of Oncology at Johns Hopkins. His lab studies the mechanisms and consequences of genetic aberrations in cancer, and strategies to target them. Much of the lab’s work focuses on the spliceosome gene SF3B1, using functional studies of human cell models, primary cancer samples, and mouse xenografts. He is also an attending oncologist at the Sidney Kimmel Comprehensive Cancer Center.

Acknowledgement of Support

“Receiving the 2025 AACR‑Ocular Melanoma Foundation Miriam Counts Innovation and Discovery Grant provides critical support for me and my laboratory in ocular melanoma research. This funding also enables testing of key next steps in developing a novel therapeutic for SF3B1‑mutant uveal melanoma.”

Scientific Statement of Research

The Siglec (sialic acid-binding immunoglobulin-like lectin) family of glycan-binding immune receptors are emerging as attractive targets for cancer immunotherapy. Regulation of sialic acids has been correlated with poor disease outcome in uveal melanoma, but the role of sialic acid–Siglec axis in this type of melanoma remains understudied. Dr. Riley aims to define the repertoires of Siglec ligands in uveal melanoma, including the protein themselves and their glycosylation states. He anticipates that this work will generate technologies for interrogating glycoprotein-Siglec interactions and will generate actionable targets for therapies that leverage this emerging immunotherapy axis.

Biography

Dr. Riley, originally from Louisville, Kentucky, earned his bachelor’s degree in Chemistry from the University of South Carolina, and his doctoral degree at University of Wisconsin-Madison. His graduate work on mass spectrometry instrumentation and proteomics methodology introduced him to glycoprotein analysis. During his postdoctoral research at Stanford University, he developed tools to characterize mucin-domain glycoproteins and cell-type specific secretomes. Since joining the University of Washington in 2023 as an assistant professor in the Department of Chemistry, his group has been leveraging state-of-the-art mass spectrometry and chemical glycobiology to investigate glycoproteome regulation.

Acknowledgement of Support

“This AACR‑Ocular Melanoma Foundation Miriam Counts Innovation and Discovery grant opens new and exciting directions of study in my group, allowing us to turn our interests in cancer glycobiology to the ocular melanoma field. Now we will be able to establish preliminary work that will generate several lines to study to pursue new axes for therapies for ocular melanoma.”