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Biology subjects

Nguyen, L. L.

Publications and source records attributed to Nguyen, L. L..

2 recordsLinked to original sources

TO BE OR NOT TO BE A PI: ADVICE FOR TRAINEES IN THE BIOMEDICAL/BASIC SCIENCES

When a biomedical or basic science doctoral (PhD) student considers whether or not to become a Principal Investigator (PI), they typically base their decisions on anecdotal data from a limited number of faculty mentors. Alternatively, they may look online for guidance and be met with biased opinions rather than unbiased, comprehensive data. We sought to address this gap by anonymously surveying active faculty at the University of Colorado Anschutz Medical Campus (CU Anschutz) to gain more clarity on the daily life of a PI, the decisions they made as they navigated their career path, and which skills were valuable for securing a faculty position. We also identified important factors in choosing a postdoctoral lab. We found that the majority of PIs would recommend becoming a PI and thought positively of the career path, with most feeling content. But attitudes differed between faculty of different ranks. Further, in addition to scientific vision, hard work, and publications, luck was also deemed as an important factor in becoming and succeeding as a PI. We present our findings so that they may serve as a resource for graduate trainees who are considering a PI/academic research career path. In addition, the information may guide future training plans to optimize achievement of their dream career.

scientific communication and education↗

Combinatory EHMT and PARP inhibition induces an interferon response and a CD8 T cell-dependent tumor regression in PARP inhibitor-resistant models

Euchromatic histone lysine methyltransferases 1 and 2 (EHMT1/2), which catalyze demethylation of histone H3 lysine 9 (H3K9me2), contribute to tumorigenesis and therapy resistance through unknown mechanisms of action. In ovarian cancer, EHMT1/2 and H3K9me2 are directly linked to acquired resistance to poly-ADP-ribose polymerase (PARP) inhibitors and are correlated with poor clinical outcomes. Using a combination of experimental and bioinformatic analyses in several PARP inhibitor resistant ovarian cancer models, we demonstrate that combinatory inhibition of EHMT and PARP is effective in treating PARP inhibitor resistant ovarian cancers. Our in vitro studies show that combinatory therapy reactivates transposable elements, increases immunostimulatory dsRNA formation, and elicits several immune signaling pathways. Our in vivo studies show that both single inhibition of EHMT and combinatory inhibition of EHMT and PARP reduces tumor burden, and that this reduction is dependent on CD8 T cells. Together, our results uncover a direct mechanism by which EHMT inhibition helps to overcome PARP inhibitor resistance and shows how an epigenetic therapy can be used to enhance anti-tumor immunity and address therapy resistance.

cancer biology↗