Research Focus

Dr. Fei's research interests focus on how tumor suppressors function and what can be learned from cancer susceptibility syndromes. She has been studying two tumor suppressor-signaling pathways, the p53 and Fanconi Anemia (FA)-BRCA signaling pathways, and their implications in tumor suppression and cancer treatment for more than two decades.

Dr. Fei started to study p53 in 1995, then she was a graduate student of Thomas Jefferson University under the mentorship of Professor Edward Mercer. She continued studying p53 for her postdoctoral research under the mentorship of Professor Wafik El-Deiry at Howard Hughes Medical Institute (HHMI), University of Pennsylvania. The importance of p53 in tumor suppression is illustrated by the fact that more than half of all human cancers have p53 mutations. During tumor development or progression, cell outgrowth generates many stresses that can activate p53 to eliminate the stressed out cells. However, the mechanisms underlying the tumor suppressor activity of p53 initiated by these stresses remain under-investigated. Dr. Fei and colleagues are among the first to study how p53 tumor suppressor activity is triggered by one tumor environment stressor—hypoxia. The goal of Dr. Fei and her colleagues in furthering p53 research is to advance the understanding of the dynamics in tumor environment and provide novel insights into developing improved diagnostic and predictive measures, as well as therapeutic methods.

During her postdoctoral studies, Dr. Fei also had an opportunity to engage in the research on Genome Instability and Chromatin-Remodeling under the mentorship of Senior Investigator, Weidong Wang at the laboratory of Genetics (LG) & Genomics of National Institute on Aging, then LG was led by NIH Distinguished Investigator, David Schlesinger. Her Fanconi Anemia (FA) research was started there (2003). FA is a rare human genetic disease with an extremely high cancer incidence, suggesting that the FA signaling pathway is a tumor suppressor pathway. With discoveries that breast cancer susceptibility gene products, BRCA1, BRCA2, PALB2, and BACH1/BRIP1 are FA proteins, the signaling pathway comprising all FA proteins that is also called the FA-BRCA tumor suppressor pathway, has become an intense area of investigation. Over the last two decades, Dr. Fei's program has provided previously unrecognized facts that can demonstrate roles of abnormal FA signaling in promoting the neoplasm in patients without FA. Their work has revealed new molecular contexts by which FA signaling performs anti-neoplasm activities in general populations. Such molecular contexts include the interactions of the FA pathway with Human Homolog of yeast rad6 (HHR6) pathway under stressed conditions to promptly repair damaged DNA, and the association of the basal-level activated FANCD2 with MCM (Mini-Chromosome Maintenance) helicase complexes for the timely fire of replication origins under non-stressed conditions. Among these novel contexts they revealed, the identification of a new variant of FANCL (FAVL-an oncogenic factor by inactivating FA signaling), was the first to demonstrate tumor-suppressor roles of FA signaling in non-FA human cancers. Dr. Fei and her team members also showed two faces of aberrant FA signaling, not only losing the tumor suppressor activities performed by the activated form of FANCD2, but also the inactivated form of FANCD2 gains new properties of up-regulating ΔNp63 - an oncogenic factor. In addition, they found that two versions of the center protein of the FA signaling, FANCD2, can be a game changer for neoplastic transformation. These studies have established her as a top expert in the field of FA signaling research, as seen in the two invited reviews from Cell Press Journals, Trend in Cancer (TIC) and Trend in Genetics (TIG). Recently, she and her colleagues have started to focus on the roles of biological variations expressed significantly in native Hawaiians in leading to a series of pathobiological alterations relevant to the FA signaling, as compared to other ethnic groups to advance our understanding the pathobiology of Native Hawaiian’s cancer health disparities. To better define cancer health disparities, she and her colleagues have also begun to explore the influences of social determinants.