Prostate cancer (PCa) is the most frequently diagnosed malignancies among men worldwide and the second leading cause of cancer related deaths in the United States. Cancer is a multifaceted condition in which a cell begins dividing in an irregular manner due to various factors including mutations in genes. Our lab recently demonstrated that JunD plays an essential role in the proliferation of PCa cells and genes involved in cell cycle progression. In this study, utilizing genomic and proteomic analyses, we identified several JunD dependent genes involved in cell proliferation with c-MYC as the key downstream regulator. We further investigated whether c-MYC is required for JunD-mediated proliferation by targeting c-MYC protein in cells overexpressing JunD (D1). DU145 and D1 cells were treated in the presence or absence of JQ1, a c-MYC inhibitor, at specific time points. c-MYC inhibition by JQ1 resulted in a decrease in cell proliferation, cell cycle arrest in the G1 phase concomitant with a decrease in several JunD dependent genes. Our data suggests there is an effective approach to block prostate carcinogenesis by inhibiting JunD dependent cell cycle genes.

Bacterial biofilms are aggregates of bacteria engulfed in a matrix that display a strong resistance to external insults. Using commensal Neisseria species,  N. elongata, N. cinerea, and N. mucosa, we tested their ability to form biofilms in the presence of physiologically relevant concentrations of spermidine. Our hypothesis is that spermidine will impair biofilm formation by commensal Neisseria, as it was shown for N. gonorrhoeae. We performed static model biofilm assays on commensal Neisseria species and measured biofilm formation at various concentrations of spermidine (0 mM, 0.5 mM, and 4mM). Our results show that N. elongata increased biofilm formation as spermidine concentration increased. N. mucosa formed a stronger biofilm at 0.5 mM spermidine compared to the other two concentrations. N. cinerea showed minimal biofilm formation compared to the other species, however, it displayed increased biofilm formation at 4 mM spermidine. In conclusion, commensal Neisseria behave differently than N. gonorrhoeae, a closely related species, which displays impaired biofilm formation in the presence of spermidine (4 mM). Next, we will focus on this discrepancy, and identify what genes are involved in biofilm formation for commensal Neisseria, and how they differ from pathogenic Neisseria.
 

Neisseria gonorrhoeae is an obligate human pathogen that causes gonorrhea, a sexually transmitted disease in humans that is becoming untreatable given high levels of antibiotic resistance expressed by N. gonorrhoeae. N. gonorrhoeae was shown to form biofilms in vivo and in vitro. Biofilms are aggregates of one or more types of microorganisms growing on different surfaces. Biofilms are important because they increase bacteria’s resistance to antibiotics and host defenses. Here, we analyze whether the commensal (non-pathogenic) species N. lactamica, a relative of N. gonorrhoeae, can provide insight on biofilm formation by Neisseria species. Our hypothesis is that N. lactamica will produce a biofilm, similarly to N. gonorrhoeae. We performed static model biofilm assays and measured biofilm formation, as previously described. Our results show that N. lactamica can form a stable biofilm in vitro. In conclusion, our hypothesis can be accepted. To further this research, the biofilms can be tested in the presence of polyamines since polyamines impair biofilm formation of N. gonorrhoeae. This would help understand whether related species behave similarly in the presence of this physiologically relevant compound.