Zhang Lab

Cellular DNA is under constant threat of damage by exogenous and endogenous sources. Exposure to chemotherapeutic agents and ionizing radiation inflicts double-strand breaks (DSBs) on DNA, which are particularly lethal to cancer cells. Additionally, cell-intrinsic factors such as cell metabolism products generate DNA replication barriers that may lead to replication stress-associated DSBs. DNA damage responses (DDR) counteract these threats and are critical for cell survival when faced with genomic instability and DNA damage induced by chemotherapy and radiotherapy or other targeted therapeutic agents. Thus, DDR system protein components have been identified as promising avenues for cancer therapeutics. However, the main challenges are identifying which patients benefit from such treatments, and how to optimize the use of such inhibitors. In addition, compelling evidence now links DDR deficiency/inhibition with the activation of anti-tumor immunity. Thus, the question remains, how can the pharmacological fine-tuning of innate/adaptive immunity responses, by interrupting DDR in cancer cells, improve cancer immune therapy? Also, despite advances in cancer therapy, new cancer treatment options remain limited due to drug resistance, therefore, new targets are desperately required. To this end, my research has focused on biomarkers predicting responses to DDR inhibitors, on cross-talk between DDR and cancer immunotherapies, and on new targets to overcome drug resistance. We are interested in lung, breast, and ovarian cancer models.

My goal is to provide a molecular foundation for instigating precise and bespoke treatment plans for individual patients by studying predictive biomarkers in response to DDR inhibitors. Also, my aim is to identify new approaches and targets for cancer treatments by conducting basic and cutting-edge translational scientific research. I am passionate about my research and hope our research will save lives and improve the quality of life for cancer patients.

The ongoing projects in my laboratory are:

1. The identification of predictive biomarkers in response to inhibitors targeting DDR, with a focus on inhibitors targeting the replication stress response proteins ATR and CHK1.
2. The identification of optimal combinations of DDR inhibitors and radiotherapy/chemotherapy/targeted therapy/immunotherapy.
3. Unraveling the interplay among DDRs, cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation, and anti-tumoral immunity.
4. The identification of new targets overcoming drug resistance by targeting epithelial-mesenchymal transition processes and cancer stem cells.

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