Advances in translational science require innovative solutions, and engagement of productive transdisciplinary teams play a critical role. While various forms of scientific meetings have long provided venues for sharing scientific findings and generating new collaborations, many conferences lack opportunities for active discussions. We describe the use of an Un-Meeting to foster innovative translational science teams through engaged discussions across multidisciplinary groups addressing a shared theme. The Un-Meeting was delivered by the University of Rochester Center for Leading Innovation and Collaboration, the national coordinating center for the National Institutes of Health Clinical and Translational Science Awards (CTSA) program. This pilot CTSA program Un-Meeting focused on engaging translational scientists, policy-makers, community members, advocates, and public health professionals to address the opioid crisis. The participant-driven format leveraged lightning talks, attendee-led idea generation, and extensive breakout discussions to foster multidisciplinary networking. Results indicated participation by a broad set of attendees and a high level of networking during the meeting. These results, coupled with the growth of the Un-Meeting across the CTSA Consortium, provide practices and models to potentially advance team and translational science. While future work will further assess the impact of Un-Meetings, this format presents a promising approach to enhance translational science.

OBJECTIVES/GOALS: Anti-cancer therapies, such as chemotherapy, can induce senescence. Senescent cells may produce factors that can promote tumor progression. In this study, we will investigate the effect of senolytics and anti-cancer treatment on fibroblasts, which are a part of the tumor microenvironment, and patient-derived colorectal cancer organoids. METHODS/STUDY POPULATION: We will induce senescence in fibroblast lines via irradation. Induction of senescence will be confirmed by monitoring SASP production, changes in morphology and proliferation rates, and senescence-associated b-galactosidase activity. To investigate the efficacy of senolytics on senescence-induced fibroblasts and CRC tumor organoids, we will creat a dose response curve and calculate IC50 values for proliferating fibroblast, senescent fibroblasts and CRC organoids. To identify the synergistic effects of anti-cancer and senolytic compounds, including Navitoclax and Dasatinib, on fibroblasts and CRC organoids, we will create dose matrixes using senolytics at concentrations that were shown to have senolytic activity and drugs from an anti-cancer library. RESULTS/ANTICIPATED RESULTS: If senescence is induced in the fibroblast lines, we expect to see no changes in confluency over 4 days, the morphology will change from a thin, spindly shape to a flattened shape, and senescence-associated b-galactosidase activity will be observed. After the fibroblast lines are treated with potential senolytic compounds, we would expect to see decreased viability in the senescence-induced fibroblast lines when compared to proliferating fibroblast lines. We predict that the viability of CRC organoid lines will slightly decrease at high concentrations of the senolytic due to overall toxicity. We expect that the senolytic and anti-cancer compounds will have a synergistic effect. Senolytic activity could reduce the senescent cell population that was developed in response to anti-cancer therapy. DISCUSSION/SIGNIFICANCE: There is an increased interest in identifying compounds that selectively promote apoptosis in senescent cells. This study uses a cell-based approach to validate senolytic activity of compounds with senolytic potential in senescence-induced fibroblast lines and investigates the synergistic effects of senolytics and anti-cancer compounds on CRC.