Peiwen Fei, MD, PhD

Peiwen Fei, MD, PhD

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Full Member, Cancer Biology Program, University of Hawaiʻi Cancer Center

Academic Appointment(s):
Professor (Researcher), University of Hawaiʻi Cancer Center, University of Hawaiʻi at Mānoa
Graduate Faculty, Cell and Molecular Biology (CMB); Molecular Biosciences & Bioengineering (MBBE), John A. Burns School of Medicine, University of Hawaiʻi at Mānoa

MD, Xu Zhou Medical College, Xu Zhou, China
PhD, Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, PA
Fellowship, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA
Fellowship, National Institute on Aging, National Institutes of Health, Baltimore, MD

Research Focus

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

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 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.

FA is a rare human genetic disease with an extremely high cancer incidence, suggesting that a FA signaling pathway is a tumor suppressor pathway. With discoveries that breast cancer susceptibility gene products, 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 ten years, 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 we 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. Furthermore, Dr. Fei and her team members showed two faces of aberrant FA signaling, not only losing the tumor suppressor activities performed by the activated form of FANCD2, the inactivated form of FANCD2 also gains new properties of up-regulating ΔNp63 - an oncogenic factor. All of these known studies together with the ongoing center on unraveling cancer mechanisms and resulting implications in cancer prevention, etiology & treatment.

Selected Publications

Hokutan, K. et al and Fei, P*. (2020). TFG-Maintaining Stability of Overlooked FANCD2-V2 Confers Early DNA-Damage Response. Aging (Albany NY); Oct 24;12(20):20268-20284. doi: 10.18632/aging.103782. Epub 2020 Oct 24.PMID: 33099537.

Che R, et al, Fei P*. (2018). Multifaceted Fanconi Anemia Signaling. Trends Genet; Mar;34(3):171-183.

Han B, et al and Fei, P*. (2017). HDBR1 Modulates U2 snRNP Function to Maintain RNA Populations, Contributing to P53 Tumor Suppressor Activity. Oncogene; Sep 21;36(38):5382-5391.

Jayabal P, et al and Fei P*. (2017). Involvement of FANCD2 in Energy Metabolism via ATP5 alpha. Scientific Report, Jul 7;7(1):4921. doi: 10.1038/s41598-017-05150-1. PMID:28687786

Zhao D, et al and Fei P*. (2010). FAVL Disrupts Fanconi Anemia Pathway and Promotes Chromosomal Instability and Tumor Development. J Clin Invest;120,1524 (May 3, 2010). PMID: 20407210.

Publication list via PubMed

Active Grants

P. Fei, Contact PI
2U54CA143727 (Pilot Project)
"New insights into the Gastrointestinal (GI) Pathobiology for Native Hawaiians/Pacific Islanders"
09/01/2021 – 08/30/2022