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 follow a circadian rhythm generated by an endogenous circadian clock. Recent studies have shown that disruption of circadian rhythms increases the risk of cancer development, accelerates tumor progression and impedes anticancer treatment in both humans and animal models. These findings indicate that the circadian clock plays an active role in tumor suppression and anticancer therapy.
The mammalian circadian clock is composed of circadian input and output 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 the key steps of diverse cellular processes including cell proliferation and metabolism. Since loss of homeostasis in cell proliferation and metabolism plays a key role in cancer development and progression as well as the resistance to anticancer treatment, understanding the mechanism of circadian control of cell proliferation and metabolism is important for cancer prevention and therapy. Our laboratory studies the role of circadian homeostasis in cancer prevention and treatment using molecular, cellular and genetic approaches. Especially, we focus on studying 1) how the circadian rhythm in cell proliferation and DNA-damage response is generated in vivo, 2) how the circadian clock couples cell proliferation and metabolism in vivo, 3) how disruption of circadian rhythm in cell proliferation and metabolism synergistically promotes tumor development, and 4) how circadian dysfunction impedes anticancer treatment. Our studies will lead to developing novel strategies for cancer prevention and treatment.
Baylor College of Medicine
1100 Bates Street, Rm. 5074
Houston, TX 77030
- 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.