Kelly Banas & Lauren Skelly
ChristianaCare, Gene Editing Institute
ARC – Spatial Analysis of CRISPR Gene Editing Outcomes in Solid Tumors
Cancer remains a leading cause of death and despite treatment advances, durable clinical responses remain limited. Tumors exploit complex mechanisms promoting survival and resistance to therapy. Local drug delivery can help overcome biological barriers associated with systemic administration. CRISPR/Cas gene editing enables precise targeting of disease-causing genes and can be delivered to solid tumors via lipid nanoparticles. However, how CRISPR-induced edits are executed and organized within tumors remains poorly understood. In partnership with Corrixr Therapeutics, we will analyze xenograft tumor samples using spatial transcriptomics and protein imaging, establishing a spatial data analysis pipeline to maximize insight from in vivo studies.
Bruce Boman
Co-PI: Gilberto Schleiniger
ChristianaCare, Helen F. Graham Cancer Center & Research Institute
iHIT – Transforming Precision Oncology: Phase 0 Lead-In Study of an Innovative Drug Combination Guided by Kinetic Modeling
Our Goal is to launch a new treatment for advanced colorectal cancer (CRC) patients based on our research discoveries made in the Center for Translational Cancer Research (CTCR) in collaboration with the University’s Center for Application of Mathematics in Medicine (CAMM). The trial translates bioscience research on simulation treatment kinetics and pre-clinical biological development stages into an innovative treatment for CRC patients. Our multi-disciplinary research team has been working for over 10 years to identify novel anti-cancer targets that can’t be identified using biological experimentation. Indeed, using mathematical modeling we discovered that suppressing WNT signaling sensitizes human CRC to the differentiation-inducing effects of retinoic acid (RA) agents. In biological experiments, we discovered that WNT and RA pathways are functionally linked, and in CRC, APC mutation of the adenomatous polyposis coli (APC) gene generates a WNT:RA imbalance leading to incomplete differentiation and stem cell (SC) overpopulation. In our preclinical experiments, we tested over 10,000 drug combinations of anti-WNT agents (Sulindac) and RA agents (all-trans RA, ATRA). The results reveal WNT:RA-based drug combinations: i) produce additive or synergistic responses in CRC cell lines, ii) decrease in ALDH+ cancer SC numbers, iii) increase neuroendocrine differentiation of SCs, iv) induce anti-tumor activity in organoid cultures, and v) lead to in vivo growth inhibition (50%) of human CRCs in PDX mice. Hypothesis: Therapeutically inhibiting WNT signaling enhances the ability of retinoid agents to induce growth suppression and differentiation in CRC patients. Immediate Objectives: 1) To conduct a Phase 0 lead-in study of oral Sulindac + ATRA for 3rd line advanced disease CRC patients. 2) Use our mathematical model to determine kinetic mechanisms for ATRA metabolism to explain how serum RA levels change in patients during treatment and to guide drug dose administration. Our CAT grant provides support for a phase 0 lead-in study of toxicity and ATRA metabolism kinetics of our novel drug combination at our Center.
Nicole Donofrio
Co-PI: Harsh Bais
University of Delaware
iHIT – Call and Response: The Role of Auxin in a Delaware-Isolated, Growth-Promoting Bacterium and Its Impact on Tomato Growth
Tomato makes significant contributions to a vibrant fresh vegetable market in Delaware. However, tomatoes are plagued by numerous plant disease-causing pathogens, which are exacerbated by the state’s hot, humid climate. We propose to further characterize a Delaware native bacterium that was isolated from agricultural soils, to determine whether it may eventually be used as a soil inoculant for tomato health. We already know this strain inhibits pathogens, and we wish to determine whether it also provides growth benefits. Our strain has potential to help keep Delaware’s tomato industry thriving, and to give growers another tool to combat against multiple pathogens.
Catherine Fromen
Co-PI: Brian Kwee
University of Delaware
ARC – Enhancing NeoDC-ACT Anti-Tumor Immunity through cDC1 Persistence, EV Signaling, and Localized Delivery
Solid tumors remain difficult to treat with current immunotherapies because they suppress immune responses and limit effective activation of cancer-killing T cells. This project aims to improve a promising first-in-human cell therapy, NeoDC-ACT, which uses specialized dendritic cells generated from blood stem cells through defined biological ligands and cytokines. As an adjuvant cell therapy, NeoDC-ACT is designed to restore the abundance of functional conventional dendritic cell type 1 (cDC1s) within the solid tumor microenvironment and enhance the body’s ability to recognize and attack tumors. While these cells can effectively initiate anti-tumor immune responses, their preclinical impact is currently limited by poor survival, loss of function, and insufficient persistence following long-term cryopreservation and after administration into the suppressive tumor microenvironment.
To address this challenge, we will develop two complementary strategies to enhance cDC1 function after delivery. First, we will engineer injectable biomaterial depots that localize cells at the tumor site and provide a supportive microenvironment through controlled release of immunomodulatory signals. Second, we will apply a nanoparticle-based pre-conditioning approach to program cDC1 cells prior to delivery, enhancing survival, activation, and extracellular vesicle (EV)-mediated immune signaling. These EVs represent an additional mechanism for antigen presentation and immune communication that may sustain T cell activation even after cell function declines. We will evaluate these approaches using human cell-based systems, including tumor spheroids and macrophage co-culture models that mimic suppressive tumor microenvironments. Key outcomes will include improved cell viability, retention of activation markers, cytokine production, antigen presentation capacity, and EV signaling profiles. Together, these studies will define how localized delivery and cell-intrinsic programming can be combined to improve the durability and efficacy of cDC1 therapies.
This project is enabled through a partnership between the University of Delaware and Cell BioEngines, supporting translation of this work toward clinical application while contributing to growth of Delaware’s biotechnology sector.
Jung Youn Lee
Co-PI: Chi Keung Lam
University of Delaware
ARC – Orthogonal Analytics-Guided Optimization of Plant-Derived AAV6
Many rare genetic diseases have no conventional drug treatments, but an emerging technology called gene therapy is changing that. Yet current manufacturing platforms remain highly costly, creating a significant barrier to patient access. Professor Jung-Youn Lee’s lab at the University of Delaware has developed a technology to produce gene therapy vectors at low cost by using plants as an alternative bioreactor platform. In this project, a collaborative research team of the Lee lab, Dr. Rui Chen’s group at Waters/Immerse Delaware (the industry partner), and UD professor Chi Keung Lam will establish a data-driven optimization workflow for plant-derived viral vectors. The Lee lab will systematically vary production parameters to identify conditions that optimize vector yield and quality. Waters/Immerse Delaware will perform orthogonal analytical characterization using their state-of-the-art mass spectrometry instruments to quantify critical quality attributes of the plant-produced vectors. These analytical outputs will feed back iteratively into the production design framework, enabling data-driven process refinement rather than empirical trial-and-error. Lam will assess the functional efficacy of the optimized plant-produced vectors in mammalian cell culture and mouse models. By combining a low-cost production platform with rigorous analytical and functional characterization, this project is expected to generate the data needed to evaluate quality and efficacy benchmarks.
Brian Nam
Co-PI: Jennifer Sims-Mourtada
ChristianaCare, Helen F. Graham Cancer Center & Research Institute
ARC – Development of an Early Detection Lung Cancer Marker
Lung cancer remains the number one cancer-related mortality in the US and is responsible for 33% of cancer deaths in Delaware. It is too often found at an advanced stage when treatment options are limited and survival rates are poorest.
Low-dose CT screening has reduced lung cancer mortality by 20%; however, it has also increased the detection of many indeterminate pulmonary nodules. Current diagnostic approaches lack accuracy in distinguishing what is benign from malignant, leading to repeated imaging tests, invasive procedures, and patient anxiety. In the U.S. alone, skin, breast, and lung cancer screening efforts have generated roughly 336K ambiguous biopsy results each year—representing an estimated $906M in unnecessary health care costs. A better test is needed to improve diagnostic accuracy.
This project will validate the first molecular assay to detect lung cancer earlier, by visualizing loss of imprinting (an epigenetic alteration) at the single-cell level. This assay has been evaluated in over 400 patients outside the U.S. and has been published in multiple high-impact journals. The test involves the collection of a simple bronchoalveolar lavage sample which is standard of care when performing routine bronchoscopy.
In partnership with LisenID, a Delaware based biotechnology company, we will generate critical U.S.-based validation data to support regulatory approval and move towards commercialization. The goals are to adapt a machine learning model to optimize accuracy and leverage clinical expertise through the well-established, Lung Health Program at the Helen F. Graham Cancer Center.
Successful completion will improve early detection, reduce unnecessary procedures, and lower healthcare costs. It will also support the growth of Delaware’s biotechnology sector by fostering industry-academic partnerships and creating high-quality jobs in diagnostics development and clinical research.
Sunitha Sadula
Co-PIs: Michael Crossley, David Owens
University of Delaware
EPoC – Advancing Plant-Derived Novel Insecticidal Actives: De-Risking Through Targeted Data Generation for Commercial Potential Evaluation
Chemical pesticides represent a ~$70 billion global market and are essential for agriculture, but they are well-recognized pollutants that threaten biodiversity and ecosystem health. While the global pesticide supply chain remains heavily dependent on foreign imports. Biopesticides offer
a safer alternative but are constrained by limited supply. In UD team’s recent innovation, nextgeneration insecticide active ingredients were synthesized from abundant domestic biomass waste (patent pending technology). With previous DBI-CAT funding (2024), we built a
first‑of‑its‑kind, multiscale model driven product-by-design framework eliminated slow, trial-and error discovery process that typically takes years. Then, the top predicted candidates were synthesized and evaluated against the lesser mealworm beetle (Alphitobius diaperinus), a major
poultry pest. One of the lead compounds with high efficacy was further assessed by Eurofins for contact toxicity to honeybees (Apis mellifera), as a measure of eco-safety. Our compound howed orders-of-magnitude lower toxicity to pollinators than conventional and newer safer insecticides. Collectively, these results showed that our leads meet all three “nice-to-have” criteria of modern pesticides: targeted efficacy, low pollinator toxicity, and preliminary evidence of a new or distinct mode of action (MoA). We successfully achieved previous DBI-CAT objectives. However, engagement with leading agrochemical companies, including FMC (Letter of Support attached) and BASF, we identified that critical commercial potential decision data is still missing. Without this data the proof-of-concept remains incomplete and neither market fit, regulatory viability, nor investment readiness can be reliably assessed. Given the decade long timeline and ~$250 million cost of pesticide development, addressing these critical gaps early is critical. Thus, further funding is necessary to pursue these three industry-informed objectives:
- Perform synthesis scale-up and technoeconomic analysis
- Evaluate toxicity against both Delaware-relevant and globally significant pests
- Establish dose-response and time-to-knockdown survival curves
The success of this project will complete the proof-of-concept data package, form a new company, strengthen SBIR/STTR proposals across USDA, NSF, DOE, and EPA, and position the technology for industry partnerships while benefiting human health and natural resources.
Shuo Wei
Co-PI: Karl Schmitz
University of Delaware
iHIT – Development of Probes and Inhibitors for ADAM9
This multi-PI iHIT application aims to develop probes and inhibitors of a disintegrinand metalloproteinase 9 (ADAM9) for research and clinical applications. ADAM9 is a cell-surface protease that has emerged as a promising biomarker and therapeutic target for multiple human diseases, including solid tumors, inflammation, autoimmune diseases, and severe COVID-19. This application leverages the unique and complementary skill sets of two PIs: Dr. Wei is an experienced researcher specializing in metalloproteinase biochemistry and cell biology, and Dr. Schmitz is a structural biologist and biophysicist ocusing on protease structure-function relationship. The proposed research project is built upon the PIs’ recent ultra-high-throughput cellular DNA-encoded library screen, which yielded 20 candidate hit compounds that selectively bind cell-surface ADAM9. AI-assisted structural modeling predicts that some of these hits may inhibit ADAM9 protease activity. The application has two aims. Aim 1 (led by Dr. Schmitz) will identify lead compounds that selectively bind ADAM9; Aim 2 (led by Dr. Wei) will generate potent and selective inhibitors of ADAM9. We will use highly innovative, state-of-the-art techniques to achieve these goals. At the completion of this project, we expect to identify high-quality ADAM9 binders and inhibitors that can be further developed into biosensors and drugs for research and clinical purposes, and submit a multi-PI R01 application using the data generated from this study to continue and deepen our collaboration. This project will also provide interdisciplinary training opportunities for graduate and undergrad students, generate publications and intellectual properties, and lead to cross-sector collaborations and partnerships with biotech and pharmaceutical companies in the State of Delaware. Therefore, the proposed collaborative research will have a sustained and transformative
impact on Delaware economy and workforce.
