Page 27 - The Hormel Institute 2024 Annual Report

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This past year, our lab developed a new set of compounds that can inactivate a protein involved in regulating the immune
system. This protein, designated as Sts-1, is a negative regulator, meaning that it functions to suppress certain immune responses.
By inactivating this protein, these new compounds effectively stimulate the immune response. This enhanced immune response helps fight off pathogenic bacteria and fungi, and could improve the effectiveness of a number of existing anti-cancer treatments. The University of Minnesota recently filed a provisional patent for these new compounds, and we are planning to launch a start-up company to develop these as a new class of immune-stimulatory anti-infective therapy.
We also continued to work towards the devel- opment of a novel treatment paradigm for liver cancer. We identified that a metabolic protein called phosphoribosylformylglycinamidine synthase (PFAS) supports liver cancer growth. We are using structural biology (Figure) and high-throughput screening to identify small molecules that can inactivate PFAS as a way to slow or stop liver cancer progression.
Using cryoEM we pick millions of particles from the raw data (A), group these particles into classes (B), and use these 2D classes to determine a 3D structure of our protein of interest (C). In this case, the structure of human PFAS (C) is guiding our efforts to identify new liver cancer treatments.
In addition, our lab again led a virtual experiential research program for undergraduate students called the Molecular Interactions Virtual Research Experiences for Undergraduates (MIV-REU) program. This unique program provides authen- tic research experiences for a cohort of under- graduate students that face barriers preventing participation in conventional in-person research programs. Barriers include financial challenges, physical disabilities, caregiver responsibilities, and other logistical challenges such as those faced by student athletes and students with non-standard academic schedules.
During the 10-week summer program, students conduct computational research to understand molecular interactions between small molecules and a target protein, as well as participating in professional development and social activities. Our summative program evaluation, led by an external independent evaluator, has shown
that nearly all of the students experienced substantial improvements in science identity and increased interest in attending graduate or professional school after participating in the MIV-REU program.