IVACS Student Oral Presentation Competition 2025

The student, Shae C. Valko, introduced the contestants during the competition.

First Place

Discovery and Initial Characterization of a Diverse Family of Microproteins Derived from Alternative Open Reading Frames in SCN(NaV) Genes

Microproteins (MPs) are a growing class of short peptides that can arise from upstream open reading frames. Recent advances in ribosome profiling have uncovered a myriad of MPs that serve vital functions in ion channel modulation, cell signaling and energetics, and more. However, there remains a need to continue characterizing novel MPs to determine their expression, function, and disease relevance. The SCN(NaV) gene family encodes voltage gated sodium channels that control sodium ion influx and trigger action potentials in excitable cells (e.g. cardiomyocytes and neurons). Our lab recently discovered a MP encoded by SCN5A (SCN5A-MP) that is generated by translation of an alternative open reading frame (altORF). We find that overexpressed SCN5A-MP can be detected in mouse hearts by western blot. In addition, a peptide matching SCN5A-MP sequence has been reported in human heart proteomics data, and western blot on human cardiac tissue lysates reveals bands co-migrating with transgene-derived SCN5A-MP. We subsequently identified several other SCN(NaV) family genes that may also encode MPs via putative altORFs. In follow-up studies, we used C-terminal V5-tagged reporter constructs to demonstrate that these altORFs are indeed translated and to assess where these altORF-derived MPs reside within cells, revealing diverse localizations. Notably, immunoblotting using custom antibodies generated against several of these altORF-derived MPs demonstrates that these are generally unstable. This reiterates the need for in vivo characterizations, particularly since peptide fragments matching these MPs have been identified in prior proteomics investigations done in human tissues. Overall, this work has uncovered the potential for several SCN(NaV) gene family members to encode a diverse panel of MPs, and future studies are needed to further characterize these and assess their potential relevance to a breadth of diseases that have been associated with this important gene family, including arrhythmias, epilepsy, neuropathy, neuromuscular disorders, and sudden death syndromes.

Jasmyn Hoeger, Department of Internal Medicine, Abboud Cardiovascular Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA. Abstract Presentation: A-1000

Second Place

Characterization of Lipid Nanoparticles for Intracranial Gene Editing

Neurological disorders like Alzheimer’s disease, Parkinson’s disease, and Rett syndrome severely diminish patients’ quality of life and place significant burdens on caregivers and healthcare systems. These disorders often stem from genetic mutations impairing neuronal function, making efficient gene editing in neurons critical for therapeutic development. Lipid nanoparticles (LNPs), with their high biocompatibility and large payload capacity, offer a promising non-viral delivery method for gene editing systems. This project optimized LNPs for the delivery of Cre/loxP mRNA to achieve efficient neuronal editing in the mouse brain. An LNP library varying in lipid ratios was screened in vitro to identify those with high transfection efficiency in Neuro-2a (neuroblastoma) and HepG2 (liver cancer) cells. Top-performing clusters, consisting of three formulations each, were further tested in vivo via intracranial injection into Ai9 reporter mouse brains. Signal colocalization quantification revealed strong neuronal editing preference in certain LNP clusters. Cluster 4 achieved up to the highest neuronal editing efficiency at 95%, followed by cluster 9 at 73% and cluster 10 at 69%, demonstrating consistency between in vitro preferences and in vivo results. While further studies are necessary to elucidate specific factors influencing neuronal transfection and editing efficiency, these findings highlight the potential of LNPs as an effective delivery method for mRNA-based therapies targeting neurons to treat neurological diseases.

Aileen Qi, Department of Biomedical Engineering, Columbia University, Bronx, NY. Abstract Presentation: A-1002

Second Place

The Diagnostic and Prognostic Utility of HSP27 in Oral Cancer

Objective: Oral Squamous Cell Carcinoma (OSCC) makes up the majority of oral cancer cases. Despite its prevalence, the five-year survival rate remains relatively low. OSCC is currently diagnosed based on histological morphology alone, which may be subjective. Identifying diagnostic molecular biomarkers such as Heat Shock Protein-27 (HSP27) could lead to earlier detection and more accurate diagnosis of oral cancer lesions. HSP27 is a chaperone that is protective against stress-induced cellular damage. Previous studies have shown conflicting trends in the overall expression of HSP27 in OSCC patients. We aim to establish HSP27 expression in oral cancer as a diagnostic biomarker. Methods: Immunohistochemistry was performed on human tissue microarray samples representing normal oral mucosa and OSCC biopsies. High-resolution images were acquired and evaluated using computer-assisted analysis. A histo-score (H-score) was calculated based on the staining intensity and the percentage of positive cells in each tissue sample. Differences in the mean H-scores were compared between normal mucosa and OSCC samples using a two-tailed unpaired T-test with P-value ≤ 0.05 set as the level of significance. Results: We found HSP27 expression to be elevated in OSCC compared to the normal oral mucosa. The differences in the mean H-scores between the two groups were statistically significant. Conclusion: The significant increase in HSP27 expression in OSCC compared to normal oral mucosa paves the way to establishing its clinical diagnostic utility. The next phase of our investigation is focused on the prognostic applications of HSP27 in oral cancer as it relates to crucial clinicopathological parameters, such as the histopathological grades/differentiation status and TNM clinical staging.

Katy Flannery, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL. Abstract Presentation: A-1003

Third Place

Panobinostat HDAC Inhibition and Its Impact on Tumor Growth in Malignant Peripheral Nerve Sheath Tumor

Malignant peripheral nerve sheath tumors (MPNSTs) are one of the most prevalent types of cancer associated with neurofibromatosis type 1 (NF-1), a common hereditary cancer predisposition condition. MPNSTs are unresponsive to typical chemotherapies, radiation, and surgical resection, leaving patients with a survival rate of 5 years or less. This experiment aims to examine the impact of Panobinostat, an extremely potent HDAC inhibitor, on the proliferation and apoptosis of polycomb-repressive complex 2 (PRC2) loss MPNST cell lines compared to PRC2 retained MPNST cell lines. Previous research has identified that loss of function alterations in PRC2, through SUZ12 or embryonic ectoderm development (EED) mutations, cause a decrease in H3K27me3, leading to excessive proliferation. To combat this decrease in methylation, Panobinostat was used to decrease proliferation and increase apoptosis of both sets of mutated PRC2 loss cell lines. The cell lines were cultured using basic cell culturing techniques in Dulbecco’s Modified Eagle Medium (DMEM) and Primocin growth media. An Incucyte machine was used for quantitative live-cell imaging and analysis every two hours for five days. Each 96-well plate consisted of a DMSO control and different concentrations of Panobinostat. After five days of treatment, the 24.3nM Panobinostat solution is the smallest concentration where impact occurred on the growth curve. While all cell lines illustrated that Panobinostat significantly reduced survival, SUZ12 and EED mutated cell lines graphically showed a decrease in proliferation compared to the wildtype retained cell line. However, the IC50 calculation did not show a significant difference between the PRC2 retained cell lines compared to the PRC2 lost cell lines. Panobinostat could be a promising drug for both patients with a SUZ12 mutation or EED mutation if research continues.

Samantha Taylor, Washington University School of Medicine, Department of Internal Medicine, Division of Oncology, St. Louis, MO and Washington University in St. Louis, CRISPr: Cancer Research Inspiring Future Scientists Program, St. Louis, MO. Abstract Presentation: A-1004