Loning Fu, Ph.D.
Departments of Molecular and Cellular Biology, Pediatrics-Children’s Nutrition Research Center and Dan L. Duncan Cancer Center
Ph.D.: University of Calgary, Calgary, Canada
Postdoctoral training: The University of Toronto, Toronto, Canada
Baylor College of Medicine, Houston
The Role of the Circadian Clock in Cancer Development and Therapy
Most physiological processes in mammals display circadian rhythms. These rhythms are generated by an endogenous time machine: the circadian clock. Recent studies have shown that disruption of circadian rhythms increases cancer development in both humans and rodents. In addition, loss of circadian rhythms is frequently associated with early mortality of patients with metastatic cancers. These findings indicate that the circadian clock could play an active role in tumor suppression and cancer therapy.
The mammalian circadian clock is composed of circadian input and out-put pathways, a central clock located in the suprachiasmatic nucleus of hypothalamus, and peripheral clocks in almost all peripheral tissues studied. Both central and peripheral clocks are operated by the feedback loops of circadian genes that not only operate the molecular clock, but also target non-circadian genes acting in key steps of diverse cellular processes. Recent studies, including our own, have shown that the clock-controlled genes include those acting in the key steps of cell proliferation and DNA-damage response. Since these two processes are involved in cancer development and response to cancer treatment, the study of the circadian rhythm of these processes has become critically important for cancer prevention and therapy. Our laboratory uses mice as models to study the mechanism of the circadian rhythm in cell proliferation and DNA-damage response. We are using molecular, cellular, and genetic approaches to study;
- How the circadian rhythm in cell proliferation and radiation response is generated in vivo
- How the circadian rhythm in radiation response affects key physiological processes that determine patients’ abilities to cooperate with therapy.
These studies will eventually lead to developing novel therapeutic strategies for cancer.
Lee S, Donehower LA, Herron AJ, Moore DD and Fu L. (2010). Disrupting Circadian Homeostasis of Sympathetic Signaling Promotes Tumor Development in Mice. PLoS One, 5, e10995. PMID: 20539819.
Ma K, Xiao R, Tseng H-T, Shan L, Fu L and Moore DD. (2009). Circadian Dysregulation Disrupts Bile Acid Homeostasis. PloS One, 4, e6843. PMID: 19718444.
Fu L, Patel MS, Bradley A, Wagner EF and Karsenty G. (2005). The Molecular Clock and AP1 Mediate the Leptin-dependent Sympathetic Regulation of Bone Formation. Cell 122:803-815. * equal contribution. PMID: 16143109.
Fu L and Lee CC. (2003). The Circadian Clock: Pacemaker and Tumor Suppressor. Nature Reviews Cancer 3:350-361. PMID: 12724733.
Fu L, Pelicano H, Liu J, Huang P and Lee CC. (2002). The Circadian Gene mPer2 Plays an Important Role in DNA-damage Response and Tumor Suppression in vivo. Cell 111:41-50. PMID: 12372299.
Fu L, Ma W and Benchimol S. (1999). A Translation Repressor Element Resides in the 3' Untranslated Region of Human p53 mRNA. Oncogene.18:6419-6424. PMID: 10597243.
Sutcliffe T, Fu L, Abraham J and Benchimol S. (1998). The p53-Mediated G1 Cell Cycle Arrest Pathway Is Retained in Human AML Cell Lines. Blood. 92, 2977-2979 (1998). PMID: 9763589.
Fu L and Benchimol S. (1997). Participation of the Human p53 3'UTR in Translational Repression and Activation following γ-Irradiation. EMBO J. 16:4117-4125. PMID: 9233820.
Fu L, Minden M and Benchimol S. (1996). Translational Regulation of Human p53 Gene Expression. EMBO J. 15:4392-4401. PMID: 8861966
Fu L, Ye R, Browder LW and Johnston RN. (1991). Translational Potentiation of mRNA with Stable Secondary Structure in Xenopus. Science 251:807-810. PMID: 1990443.
For more publications, see listing on PubMed.
Baylor College of Medicine
1100 Bates Street, Rm. 5074
Houston, TX 77030