The broad goal of the GSP is to gain new insights into the molecular pathways that maintain genome integrity, and how these processes are altered in cancer cells. The ultimate goal is to translate this information into new prevention and treatment strategies.
- Define the molecular mechanisms of genome instability leading to cancer.
- Identify novel therapeutic opportunities created by mutations in DNA repair genes.
- Examine functional interactions in telomere maintenance, cellular senescence, and cell death in the processes of cancer and aging.
- Develop strategies to sensitize and mitigate responses to ionizing radiation, genotoxic therapeutics and oxidative stress.
- Define the functional interactions between DNA damage responses with innate and adaptive immunity.
- Work with other programs to develop and support Phase 1 and Phase 2 clinical trials.
Because these subjects are overlapping and intimately linked, program members generally work in more than one of these sub-areas. By collaboration and communication, research areas within GSP work synergistically with other UPMC Hillman Cancer Center programs for translation of novel basic insights into development of new targets, drug discovery, and recognition of biomarkers – and ultimately, clinical application to specific cancer types.
Aging and Cancer
Researchers participating in this research theme aim to better understand functional interactions between telomere biology, chemotherapeutic-induced aging, cellular senescence and cell death pathways.
Genotoxic Stress Responses
The research within this theme seeks to define the functional interactions between DNA damage responses and genotoxic stress during replication, cell cycle checkpoints, inflammation, and immune responses.
Mechanisms of Genome Stability
A major focus of this research theme is to understand the molecule mechanisms of DNA repair and factors that dictate pathway choice. This fundamental knowledge could lead to novel therapeutic opportunities given the importance of genome instability in cancer.
This theme focuses on DNA repair pathways dedicated to removing oxidative DNA damage stemming from ionizing radiation, genotoxic therapeutics and oxidative stress, with the overall aim of developing strategies to sensitize or mitigate cellular responses to this oxidant injury.