Nuclear Dynamics and Cancer

The mission of the Nuclear Dynamics and Cancer (NDC) program is to tackle mechanistic problems controlling nuclear function, while devising strategies to translate basic science findings into biomarker studies and/or clinical trials. The NDC program faculty members address key concepts about how proper packaging and regulation of DNA impacts genome integrity, gene regulation and epigenetic mechanisms in normal and cancer cells, while establishing how these insights are impacting therapeutic opportunities.

NDC members are addressing three main themes: Genome Integrity, Gene Regulation and Epigenetic Mechanisms and Therapeutic Response:

1. Genome Integrity. Genome instability and mutations are hallmarks of cancer. NDC faculty are studying key germline and somatic DNA Damage Response (DDR) mutations promoting cancer and altered therapeutic response. Furthermore, investigators are assessing the interplay that DNA structure and epigenetics has on genome integrity. These efforts are complimented by efforts to identify how DDR and epigenetic factors are impacting cancer cell vulnerabilities. These studies are conducted at the most basic science level, while being assessed in a translational context so that treatment and novel therapeutic options are developed.
2. Gene Regulation. Gene regulation plays a fundamental role in cell fate, division, immune function, DNA damage regulation and genome stability. Understanding how key genes involved in therapeutic response and resistance as well as DDR has important consequences in understanding tumorigenesis and in properly therapeutically targeting cancer. NDC faculty interrogate how gene regulation plays a role in normal and cancer cells with the goal of understanding tumorigenesis and establishing the link to therapeutic opportunities. These studies are conducted in both the laboratory and clinical settings in order to better impact our catchment area.
3. Epigenetics and Therapeutic Response. Modulating genome organization and the epigenome are critical in regulating gene expression, genome stability, and DNA repair. Epigenetic mis-regulation is a cancer hallmark and provides a unique opportunity to therapeutically target tumors. NDC members investigate epigenetic mechanisms regulating the DNA modifications and/or chromatin modification states impacting tumorigenesis and therapeutic response with the goal of identifying candidate epigenetic biomarkers that can be used to guide conventional and novel therapeutic strategies. NDC members leverage novel epigenetic therapies individually and/or in combination with other therapies in order to target cancer in our catchment area.

While laboratory research in the program is mechanistically focused, the program is active in outreach to extend the highlights of research finding to other patients, caregivers, and legislatures. We have embedded community members into the program. The community education and advocacy also help build relationships with individuals with diverse backgrounds and experiences with our Community Outreach and Engagement office. Our efforts aim to enhance the bi-directional interactions and education and science that will impact Pennsylvania legislation in regard to firefighter risk, screening and treatment. These efforts are actively underway and have included the PA Cancer Coalition Leadership. The scientific studies related to these efforts are fostered by the incorporation of faculty studying genome integrity, gene regulation and epigenetics. Therefore, the science and community impact are integrated into the themes and research efforts in the program.