Loning Fu, Ph.D.
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Loning Fu, Ph.D.
Associate Professor
Positions
- Associate Professor
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Medicine/MCB
Baylor College of Medicine
Houston, Texas United States
- Member
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Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
Education
- Post-Doctoral Fellowship at Ontario Cancer Institute
- Toronto, Ontario Canada
- PhD from University Of Calgary
- Calgary, Alberta Canada
- MSc from Academia Sinica
- Beijing, China
- Post-Doctoral Fellowship at Baylor College Of Medicine
- Houston, Texas United States
- BSc from Beijing University
- Beijing, China
Websites
THE ROLE OF CIRCDIAN HOMEOSTASIS IN CANCER PREVENTION AND THERAPY
Evolutionary adaptation dictates that most physiological processes in mammals follow a circadian rhythm, which in all species studied is generated by an endogenous circadian clock. The circadian clock constantly couples internal physiology with external environmental cues to provide the best fitness. Recent studies have demonstrated that the prevalence of chronic circadian disruption in industrialized societies due to lifestyle changes significantly increases the risk of various modern-day diseases including metabolic syndromes and cancers.
We have discovered that disruption of the mammalian circadian clock increases the risk of various types of cancer. Our current studies are focused on the role of circadian homeostasis in the prevention and treatment of obesity and metabolic syndromes as well as obesity-related cancers, such as spontaneous hepatocellular carcinoma (HCC), which is previously considered a rare type of cancer in the Western countries but is expected to become a common cancer in the 21st century due to the prevalence of obesity and obesity-related liver metabolic disorders.
Our studies intend to define 1) the role of clock-controlled neuroendocrine homeostasis in prevention of obesity and obesity-related metabolic disorders, 2) the role of liver metabolic disorders and neuroendocrine dysfunction in spontaneous HCC development and progression, and 3) the role of nuclear receptors in spontaneous HCC prevention and treatment. These studies are expected to elucidate the mechanism of cancer as a consequence of chronic malfunction in mammalian physiology and contribute to the development of novel therapeutic strategies for obesity and cancer prevention and treatment.
Selected Publications
- Fu L, Pelicano H, Liu J, Huang P, Lee C "The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo.." Cell. 2002 Oct 4;111(1):41-50. Pubmed PMID: 12372299
- Fu L, Patel MS, Bradley A, Wagner EF, Karsenty G "The molecular clock mediates leptin-regulated bone formation.." Cell. 2005 Sep 9;122(5):803-15. Pubmed PMID: 16143109
- Kettner NM. Mayo SA, Huan J, Lee C, Moore DD, Fu L "Circadian Dysfunction Induces Leptin Resistance in Mice.." Cell Metabolism. 2015 Jul 9; Pubmed PMID: 26166747
- Stashi E, Lanz RB, Mao J, Reineke L C, Kettner N, Stevenson C, Dasgupta S, Dean A, Sivasubramanian N, Reineke EL, York B, DeMayo F, Fu L, and O’Malley BW "SRC-2 is an essential coactivator for BMAL1:CLOCK in orchestrating circadian rhythm and metabolism." Cell Rep. 2014 Feb;6(4):633-45. Pubmed PMID: 24529706
- Wu N, Ho Kim K, Zhou Y, Man Lee J, Kettner NM, Mamrosh JL, Choi S, Fu L and Moore DD "Small Heterodimer Partner (NR0B2) Coordinates Nutrient Signaling and the Circadian Clock in Mice." Mol Endocrinol. 2016 Sep;30(9):988-995. Pubmed PMID: 27427832
- Fu, L & Lee CC "The circadian clock: pacemaker and tumor suppressor." Nature Rev. Cancer. 2003 May;3(350–361) Pubmed PMID: 12724733
- Ma, K., Xiao, R., Tseng, H., Shan, L., Fu, L and Moore DD "Circadian dysregulation disrupts bile acid homeostasis." PLoS One. 2009;4(e6843) Pubmed PMID: 1971844
- Fleet T, Stashi E, Zhu B, Rajapakshe K, Marcelo KL, Kettner NM, Gorman BK, Coarfa C, Fu L, O'Malley BW and York B "Genetic and Environmental Models of Circadian Disruption Link SRC-2 Function to Hepatic Pathology." J Biol Rhythm. 2016 Jul 17;[Epub ahead of print] Pubmed PMID: 27432117
- Lee J, Kim MS, Li R, Liu VY, Fu L, Moore DD, Ma K and Yechoor VK "Loss of Bmal1 leads to uncoupling and impaired glucose-stimulated insulin secretion in β-cells." Islets. 2011 Dec;3(6):381-388. Pubmed PMID: 22045262
- Fu L, Kettner NM "The Circadian Clock in Cancer Development and Therapy." Prog Mol Biol Transl Sci. 2013;119:221-282. Pubmed PMID: 23899600
- Kettner NM, Voicu H, Finegold MJ, Coarfa C, Sreekumar A, Putluri N, Katchy CA, Lee C, Moore DD, Fu L "Circadian homeostasis of liver metabolism suppresses hepatocarcinogenesis." Cancer Cell. 2016 Dec 12;30(6):909-924. Pubmed PMID: 27889186
- Kettner NM, Katchy CA, Fu L "Circadian gene variants in cancer.." Ann Med. 2014 Jun;46(4):208-220. Pubmed PMID: 24901356
- Lee S, Donehower LA, Herron AJ, Moore DD, Fu L "Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice." PLoS One. 2010 Jun 7;5(6):e10995. Pubmed PMID: 20539819
- Jennifer Padilla, Noha M. Osman, Beatrice Bissig-Choisat, Sandra M. Grimm, Xuan Qin, Angela M. Major, Li Yang, Dolores Lopez-Terrada, Cristian Coarfa, Feng Li, Karl-Dimiter Bissig, David D Moore and Loning Fu "Circadian Dysfunction Induces NAFLD-related Human Liver Cancer in a Mouse Model.." J Hepatol. 2023 Oct; Pubmed PMID: 37890720
- Alexandrou AT, Duan Y, Fan M, Tepper CG, Tang J, Berg JJ, Basheer W, Valicenti T, Wilson PF, Coleman MA, Vaughan AT, Fu L, Grdina DJ, Murley J, Woloschak G, Li JJ. "Circadian Protein PERIOD 2 Regulates Adaptive Radioprotection via PER2/pGSK3β/β-Catenin/Per2 Loop." iScinece. 2022; Pubmed PMID: 9708791
Funding
- The Study of the Circadian Rhythm in p53 Signaling/The Role of Leptin in Diet-Induced Obesity Grant funding from NIH/NCI, CPRIT and USDA
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