Gates Institute Awards $1.5 Million from Gates Grubstake Fund to CU Researchers

The Gates Institute at University of Colorado Anschutz, in partnership with CU Anschutz Innovations, is pleased to announce the recipients of its 2025 Grubstake Awards. The Institute, dedicated to advancing innovation in the growing field of cell and gene therapies and regenerative medicine, makes the awards to advance innovation in health care delivery. The newest awards support four cutting-edge projects spanning diagnostics, therapeutic platform development, and novel delivery technologies, with the potential to impact a range of serious diseases, including Alzheimer’s disease, ovarian cancer, age-related macular degeneration and rare genetic diseases.

“This year’s funded projects highlight the breadth of innovation happening across our campus,” said Gates Institute Executive Director Terry Fry, MD. “These awards support interdisciplinary work with the potential to change how we treat complex diseases. The awardees exemplify the creativity and rigor needed to advance the next generation of cell and gene therapies, and we are proud to support their work.”

The funded projects are:

• Christina Coughlan, PhD: AD-Exo as a Plasmid-Based Diagnostic for Alzheimer’s Disease
  

The onset of neuropathology in Alzheimer’s disease (AD) can precede clinical symptoms by 20 years. One of the major roadblocks in developing new interventions and understandings of AD pathology is the lack of sensitive, specific, and minimally invasive biomarkers for diagnosing, monitoring, and treating this disease. Since this devastating neurodegenerative disorder affects approximately 7 million people in the U.S. with no cure and limited therapeutic options, there is a critical need for accessible and accurate AD testing platforms. CU Anschutz Assistant Professor of Neurology Christina Coughlan, PhD, and her team, including Professor of Neurology Huntington Potter, PhD,  and Kristyn Masters, PhD, Professor and Chair in the Department of Bioengineering, have developed an Exosome-based diagnostic test (AD-Exo) that can distinguish AD patients from controls with an accuracy matching that of AD PET imaging. Notably, AD-Exo can also reliably detect sex differences in those with mild-cognitive impairment and AD; important for our understanding of the two-fold higher risks for women developing AD. The Grubstake Award will fund experiments that expand disease knowledge through increased patient monitoring enabling this team to move forward with the FDA IND application process.

• Jay Hesselberth, PhD: Universal ASO Platform for Cryptic Exon Correction Across Genetic Diseases

Antisense oligonucleotide (ASO) therapies have demonstrated remarkable clinical success for genetic diseases, but the cost of required toxicology studies remains a critical economic barrier limiting their development for rare diseases. CU Anschutz Professor Jay Hesselberth, PhD, in collaboration with Suja Jugannathan, PhD, and Scott Demarest, MD, have developed a therapeutic platform that focuses on mutation-agnostic ASO therapies targeting cryptic exon splicing defects in rare diseases. Cryptic exons arise when intronic mutations activate normally inactive splice sites, leading to inclusion of exons containing premature stop codons. The team has developed a unique approach to systematically identify clinically relevant cryptic exons across the genome. This systematic approach has generated a database of clinically actionable cryptic exon targets, providing a strategic advantage in therapeutic candidate selection compared to ad hoc target discovery approaches.  Gates Grubstake funding will enable the team to complete critical proof-of-concept validation that will transform promising laboratory discoveries into foundation-ready therapeutic candidates.

• Wyatt Shields, PhD, and Benjamin Bitler, PhD: Macrophage Backpacks for Delivering Olaparib to High-Grade Serous Carcinomas

High-grade serous carcinoma (HGSC) remains the most lethal ovarian cancer subtype. Drugs known as poly(ADP-ribose) polymerase inhibitors (PARPi), including olaparib (OLAP), are commonly used as maintenance therapy following response to platinum chemotherapy. Although OLAP provides an increased benefit for BRCA-mutated tumors, it is limited by systemic toxicities and a rare but serious risk of developing blood cancers such as myelodysplastic syndrome and acute myelogenous leukemia. Dr. Wyatt Shields, Assistant Professor in the CU Boulder Department of Chemical and Biological Engineering, in collaboration with Dr. Benjamin Bitler, Associate Professor in the CU Anschutz Division of Reproductive Sciences, and CU PhD student Courtney Bailey, addressed these barriers with a targeted delivery system utilizing a macrophage-bound discoidal particle (“backpack”; Mac-BP). Backpacks are fabricated from a biodegradable polymer that enables controlled drug release. Their discoidal geometry prevents phagocytosis, allowing stable attachment to macrophages and subsequent trafficking and delivery to tumors, thereby reducing undesirable side effects. The Gates Grubstake funding will help support readiness for IND-directed development to enable clinical translation of Mac-BPs.

• Natalia Vergara, PhD: Development of a Novel Therapy to Prevent Vision Loss in Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in adults over 60, impacting over 200 million people worldwide. Dry-AMD is the most common form of AMD, accounting for 90% of cases, for which there is currently no cure. Existing treatments can modestly slow lesion growth but fail to preserve vision. Dr. Natalia Vergara, Assistant Professor in the Department of Ophthalmology, along with Dr. Mi-Hyun Nam and Dr. Ram Nagaraj, both previous Grubstake Award recipients, and Dr. Marc Mathias, have developed a gene therapy that delivers a multifunctional peptide designed to target several of the cellular mechanisms driving dysfunction and cell death in AMD. By addressing multiple disease pathways simultaneously, this approach has the potential to limit retinal degeneration more effectively than single-target therapies. The Grubstake Award will support critical preclinical and human retinal organoid studies, positioning the team for an initial FDA INTERACT meeting and advancing this promising therapy toward clinical trials.

To learn more about the Gates Institute and its mission to bring curative therapies to patients through innovation, collaboration, and clinical translation, visit gates.cuanschutz.edu. To learn more about the Gates Grubstake Fund, click here.