傅嫈惠
Ying-Hui Fu
- Prof. Department of Neurology, University of California at San Francisco (UCSF)
- [email protected]
Lab Introduction & Major Research Interests
Major Research Interests
My research focus has been using human genetics to identify mutations that contribute to neurological conditions and sleep behaviors and then to characterize the corresponding wild-type and mutant proteins. Animal models including mouse and fly are used to recapitulate human conditions via the generation of mutation-carrying animals. In addition, in vitro experiments using cell culture, cellular biology, biochemistry, and proteomics are applied to gain understanding of new aspects of normal biology as well as molecular mechanisms of diseases and unusual sleep behaviors. Each gene that we identify provides new insights into the overall mechanism of complex pathways involved in each condition. This approach has been extremely fruitful for us in revealing the regulatory pathways of human sleep behaviors. The dominant mutations that we have identified in human repeatedly provide significant and unique insights into these pathways that could not be obtained using other traditional animal modeling approaches. To further deepen our understanding of the regulatory mechanisms of human sleep duration and efficiency at the neuro-circuitry level, we are applying emerging neuroscience technologies in our research. This will significantly expand the potential for reaching our ultimate goal of helping people obtain better health and better aging through better sleep.
Recent Representative Publication ( * corresponding author)
Establishing the field of human circadian rhythm genetics:
1. Toh KL, Jones CR, He Y, Eide EJ, Hinz WA, Virshup DM, Ptáček LJ, Fu Y-H. An hPer2 phosphorylation site mutation in familial advanced sleep-phase syndrome. Science 2001; 291:1040-3.
2. Xu Y, Padiath QS, Shapiro RE, Jones CR, Wu SC, Saigoh N, Saigoh K, Ptáček LJ, Fu Y-H. Functional consequences of a CKIδ mutation causing familial advanced sleep phase syndrome. Nature 2005; 434:640-4.
3. Zhang L, Hirano A, Hsu P-K, Jones CR, Sakai N, Okuro M, McMahon T, Yamazaki M, Xu Y, Saigoh N, Saigoh K, Lin S-T, Kaasik K, Nishino S, Ptáček LJ, Fu Y-H. PERIOD3 contributes to sleep and mood behavioral traits PNAS 2016 March 15;113(11):1536-44.
4. Hirano A, Shi G, Jones CR, Lipzen A, Pennacchio LA, Xu Y, Hallows WC, McMahon T, Yamazaki M, Ptáček LJ, Fu Y-H. A Cryptochrome 2 mutation yields Advanced Sleep Phase in human. Elife 2016 Aug 16;5. pii: e16695. doi: 10.7554/eLife.16695.
Investigating circadian phosphoproteomics and global regulation:
1. Kategaya L, Hilliard A, Zhang L, Asara JM, Ptáček LJ and Fu Y-H. Casein Kinase 1 Temporal Proteomics Reveal Prohibitin 2 Function in Molecular Clock. PLos ONE 2012; 7(2):e31987.
2. Kaasik K, Kivimäe S, Allen JJ, Chalkley RJ, Huang Y, Baer K, Kissel H, Burlingame AL, Shokat KM, Ptáček LJ, Fu Y-H. Glucose Sensor O-GlcNAcylation Coordinates with Phosphorylation to Regulate Circadian Clock. Cell Metab 2013 Feb 5; 17(2):291-302.
3. Lin S-T, Zhang L, Lin X, Zhang LC, Garcia VE, Tsai CW, Ptáček LJ, Fu Y-H. Nuclear envelope protein MAN1 regulates clock through BMAL1. Elife 2014 Sep 2; 3:e02981.
4. Hirano A, Fu Y-H, Ptáček LJ. FAD regulates CRYPTOCHROME protein stability and circadian clock in mice. Cell Report 2017, 19:255–266.
Establishing the field of human efficient sleep genetics:
1. He Y, Jones CR, Fujiki N, Xu Y, Guo B, Holder J, Nishino S, and Fu Y-H. The transcriptional repressor DEC2 regulates sleep length in mammals. Science 2009; 325:866.
2. Hirano A, Hsu P-K, Zhang L, Xing L, McMahon T, Yamazaki M, Ptacek LJ, Fu Y-H. DEC2 modulates orexin expression and regulates sleep Proc Natl Acad Sci U S A. 2018; March 12.