DNA double-strand breaks (DSBs) are caused by either endogenous agents or exogenous ionizing radiation and chemicals. Incorrect DSB repair can lead to undesired genome rearrangements. Homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways are two major DNA repair pathways that repair DSBs and maintain genome integrity. When homologous DNA is...
Glioblastoma multiforme (GBM) is the most prevalent primary central nervous system tumor, characterized by resistance to therapeutic intervention, inevitable recurrence, and ultimately patient death. The dismal prognosis is due in part to underlying molecular factors that promote an intratumoral cellular state heterogeneity and protect tumor cells from cell death pathways....
Mitochondria-derived reactive oxygen species (mROS) are required for the survival, proliferation, and metastasis of cancer cells. The mechanism by which mitochondrial metabolism regulates mROS levels to support cancer cells is not fully understood. To address this, we conducted a metabolism-focused CRISPR/Cas9 genetic screen and uncovered that loss of genes encoding...
Gene regulatory networks contain multiple components including microRNAs (miRNAs) that coordinate regulation of genes to produce higher level cell functions. miRNAs are small non-coding RNA molecules that modulate gene expression post-transcriptionally by binding to short target motifs on mRNA transcripts to down-regulate target genes. Because miRNA regulation of genes is...
Immune checkpoint inhibitors have not been effective for immunologically “cold” tumors, such as prostate cancer, which contain scarce tumor infiltrating lymphocytes. We hypothesized that select tissue-specific and immunostimulatory bacteria can potentiate these immunotherapies. Here we show that a patient-derived prostate-specific microbe, CP1, in combination with anti-PD-1 immunotherapy, increased survival and...
Post-transcriptional gene silencing (PTGS) and, more specifically, RNA interference (RNAi) include the processes by which a small double-stranded RNA, 19 to 22 nucleotides (nts) long, negatively regulates the expression and/or translatability of a target RNA, which harbors reverse complementarity to that small RNA, by recruiting the so-called RNA-Induced Silencing Complex...
DNA methylation in repetitive elements (RE) suppresses their mobility and maintains genomic stability, and decreases in it are frequently observed in tumor and/or surrogate tissues. Averaging methylation across RE in the genome is widely used to quantify global methylation. Methylation of RE in humans is considered a surrogate for global...
SIRT3 is a mitochondrial-localized, NAD+-dependent deacetylase, tumor suppressor protein that functions to direct mitochondrial energy sensing and antioxidant proteins, increasing the efficiency of energy utilization, providing a redox balanced environment, and preventing aging-related diseases. One SIRT3 deacetylation target is NADP+-dependent isocitrate dehydrogenase 2 (IDH2), a key Krebs Cycle enzyme that...
Spherical Nucleic Acids (SNAs) are nanoparticle bioconjugates that have found use in a wide-range of diagnostic and therapeutic applications. These nanomaterials are composed from inorganic or organic core nanoparticle scaffolds that are functionalized with a dense surface layer of nucleic acids (typically DNA or RNA) that are oriented in a...
Over the course of tumor growth, cancer cells interact with normal cells via processes that are difficult to understand by experiment alone. This challenge is particularly pronounced at early stages of tumor formation, when experimental observation is most limited. Eluci-dating such interactions could inform both understanding of cancer and clinical... and Tumor growth involves a dynamic interplay between cancer cells and host cells, which col-lectively form a tumor microenvironmental network that either suppresses or promotes tumor growth under different conditions. The transition from tumor suppression to tumor pro-motion is mediated by a tumor-induced shift in the local immune state, and despite...