Qi-En Wang Lab
Research over the past several years has provided ample evidence that genome instability is one of the main forces driving the onset and progression of carcinogenesis. Eukaryotic cells have developed a wide range of DNA-repair pathways to maintain genomic stability and cell viability when exposed to environmental and endogenous metabolic DNA-damaging agents. Different kinds of DNA damage need different DNA-repair pathways, which function to remove and fix the DNA lesions in a timely manner to prevent the conversion of lesions into permanent mutations in the genome. Dysfunction of components involved in these processes contributes to genomic instability, which in turn leads to tumorigenesis. Therefore, activation of DNA repair pathways is very important for maintaining genomic stability, while turning off DNA repair pathways might also be important, in particular, for chemotherapy with DNA-damaging agents such as cisplatin.
The focus of our research is on the regulation of nucleotide excision repair (NER) in the context of chromatin, and the connection of DNA repair to cancer therapy. Most recently our work has come to focus on DNA damage response in human cancer stem cells (CSCs) and their contribution to the development of chemotherapy resistance.
Cisplatin has been widely used for more than a generation to treat various malignant tumors, including ovarian, testicular, head and neck, and lung cancers. Chemotherapy with cisplatin is initially effective for most patients. However, the majority of cases eventually become refractory to cisplatin treatment. Indeed, 90 percent of deaths from ovarian cancer can be attributed to drug resistance. Poor understanding of the underlying mechanisms of this acquired drug resistance poses a critical cancer research challenge.
Our research explores the mechanisms underlying acquired cisplatin resistance. We focus on DDB2-mediated apoptosis and the role of CSCs and their genomic instability in the development of acquired cisplatin resistance.
Qi-En Wang, MD, PhD
Division of Radiobiology
Department of Radiology
1014 Biomedical Research Tower
460 W. 12th Ave.
Columbus, OH 43210
Ran Zhao, PhD, Research Associate 2
Amit Kumar Srivastava, PhD, Research Associate 1
Tiantian Cui, PhD, MD, Postdoctoral Researcher