Hepatocellular Carcinoma (HCC) is one of the main types of liver cancer accounting for 75% of cases and is the second deadliest cancer worldwide. Chronic Hepatitis B (HBV) and Hepatitis C (HCV) remain one of the most important global risk factors and account for 80% of all HCC cases. HCC also exhibits sex-differences with significantly higher incidence and worse prognosis in males. The mechanistic basis of these sex-differences is poorly understood. To identify genes and pathways that are sex-differentially expressed in viral-mediated HCC, we performed differential expression analysis on tumor vs. tumor adjacent samples that were stratified based on sex, viral etiology, and both. The differentially expressed genes were then used in a pathway enrichment analysis to identify potential pathways of interest. We found differentially expressed genes in both sexes and both etiologies. 65 genes were unique to females and 184 genes unique to males. 381 genes are unique to HBV and 195 genes are unique to HCV. We also found pathways that were significantly enriched by the differentially expressed genes. Ten pathways unique to the female tumor tumor-adjacent comparison and a majority of those pathways were a part of the cell cycle. Four enriched pathways unique to male tumor tumor-adjacent and three of them were a part of the immune system. There were no pathways unique to either etiology, but seven pathways shared by both etiologies. Two were a part of the cell cycle and one involved lipid metabolism. These differentially expressed genes and significant pathways are potential targets for individualized therapeutics and diagnostics for HCC.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the deterioration of upper and lower motor neurons in the brain, brain stem, and spinal cord. Multiple missense mutations have been connected to familial ALS, including those in the Matrin-3 protein. Matrin-3 is an RNA and DNA-binding protein encoded by the MATR3 gene. Normally found in the nuclear matrix, Matrin-3 plays several roles vital to RNA metabolism, including splicing, RNA degradation, mRNA transport, mRNA stability, and transcription. Mutations in MATR3 leading to familial ALS include P154S and S85C, but the mechanisms through which these mutations contribute to ALS pathology remain unknown. This makes mouse models particularly useful in elucidating pathology mechanisms, ultimately having the potential to serve as preclinical models for therapeutic drugs. Because of the importance of animal models, we worked to create ALS mouse models for the MATR3 P154S and S85C mutations. We specifically generated two CRISPR/Cas9 mediated knock-in mouse models containing the MATR3 P154S or S85C mutation expressed under the control of the endogenous promoter. Both the homozygous and heterozygous P154S mice developed no physical or motor defects or shortening of lifespan compared to the wildtype mice. They also exhibited no ALS-like pathology in either the muscle or spinal cord up to 24 months. In contrast, the homozygous S85C mice exhibited significant physical and motor differences, including smaller weight, impaired gait, and shortening of lifespan. Some ALS-like pathology was observed in the muscle, but pathology remained limited in the spinal cord of the homozygous mice up to 12 months. In conclusion, our data suggests that the MATR3 P154S mutation alone does not cause ALS in vivo, while the MATR3 S85C mutation induces significant motor deficits, with pathology in the spinal cord potentially beginning at older ages not examined in our study.

The Human Leukocyte Antigen (HLA) is a protein on the surface of cells that is a large component of the adaptive immune response as it helps recognize foreign pathogenic material. We wonder if a set of primers designed for each HLA type could be used to amplify a wide spectrum of HLA to improve sequencing of HLA to improve HLA-typing access. We propose the use of an HLA allele panel to determine the pulldown capacity of the primers followed by MinION sequencing and also offer a multiplexing design for running 96 patients at once. Our results show that primers can capture Class I HLA alleles and typing was successful with an average alignment accuracy of 91.7%. In conclusion this method for HLA capture could be utilized for HLA-typing with material costs of under $3.00 per sample within 3 days.