RIOK3, an Unexplored Therapeutic Target Against Cancer

Overview

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a five-year survival rate of only 13% and no effective treatment options. RIOK3, a kinase implicated in immune modulation and cytoskeletal structure, has emerged as a promising therapeutic tar get due to its overexpression in PDAC and association with tumor invasiveness and metastasis. In this project, I tested the hypothesis that selective pharmacological inhibition of RIOK3 would reduce PDAC cell proliferation and viability by disrupting its p hosphorylation. This study evaluated the pharmacological inhibition of RIOK3 using two synthesized compounds, DX809 and DX812, designed to selectively target RIOK3 by mimicking ATP to interact with its active site. Caspase - 3, MTS, and LDH assays were utili zed to assess the drug dose response by cells in the form of apoptosis, metabolic activity, and general cell death. At one nanomolar, DX809 significantly decreased cell proliferation and disrupted cytoskeletal integrity, while DX812 effectively induced cell death. The observed morphological changes of cell rounding and detachment, further suggested cytoskeletal disruption as a critical mechanism of action. Notably, the selectivity of these inhibitors implies reduced side effects in chemotherapy by sparing n on-cancerous tissues with low RIOK3 expression. The findings highlight RIOK3's role in sustaining cancer cell viability and its potential as a novel therapeutic target. Future studies should explore combination dosing of DX809 and DX812, their efficacy in vivo, and their potential interactions with other atypical kinases such as RIOK1 and RIOK2. These results offer a promising pathway for developing selective, effective treatments for PDAC and other cancers expressing RIOK3. Reducing Hydrofluorocarbon Emissions: Fine-Tuning Phase Transitions in Two- Dimensional (2D) Perovskites for Solid-State Refrigeration Ian Jake Kim West High School, Salt Lake City, UT Principal Investigator: Dr. Connor Bischak, University of Utah Common refrigerants in cooling systems contain hydrofluorocarbons (HFCs), potent greenhouse gases with global warming potentials 1000x higher than CO 2, which leak into the atmosphere upon disposal of cooling equipment. A solid -state alternative to HFCs, storing thermal energy in a solid-solid phase transition, could prevent harmful climate effects. 2D perovskites are promising solid-state refrigerant candidates due to their molecular tunability and significant enthalpy changes (ΔHtrans): the magnitude of thermal energy absorbed/released when their organic cation layer undergoes an order -to-disorder phase transition upon reaching their phase transition temperature (PTT). This study explored the thermodynamic effects of alloying different molar ratios of halides (Br-,Cl-), organic cations of varying lengths (9,10,11-carbons), and metal cations (Cu2+,Mn2+) in 2D perovskites to provide novel methods in 1) leveraging maximal ΔH trans to maximize perovskite cooling efficiencies 2) exerting control over the PTT to develop perovskites for specific temperature applications, to ultimately find viable solid -state refrigerant alternatives. Through halide and organic cation alloying, the PTT was fine-tuned over a 12℃ and 21℃ range. I found that a 100% Cl- and 100% longer organic cation (10,11-carbons) composition yielded the maximal ΔHtrans. This composition achieved a cooling efficiency half that of conventional HFCs. Findings showed that by further lengthening the organic cation, higher ΔHtrans could be leveraged to reach ΔHtrans of HFCs. Additionally, blending Cu2+ and Mn2+ had minimal effect on the PTT and ΔHtrans. Through halide and organic cation alloying, this study provided novel principles to develop solid-state refrigerants for specific temperature applications, while maintaining comparable cooling efficiencies to HFCs.

Competition history

• JSHS 2025 Category not listed

Resources

• National JSHS abstract book ↗

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