Li, Xiaodong, Ph.D.

College of Life Sciences, WuHan University, Hubei Province, 430072

xiaodli@whu.edu.cn

1993/9-1997/7: Peking Univ., B.S. in Biochemistry and Molecular Biology;

1997/9- 2002/9: Northeastern Univ., MA, USA. Ph.D. in Cell Biology;

2002/10-2004/10:Harvard Medical School, postdoc in Neurology;

2004/12 –： WuHan Univ., College of Life Sciences (Physiology).

Publications:

1.Kramer A, Yang FC, Snodgrass P, Li X, Scammell TE, Davis FC, Weitz CJ. Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling. Science. 294:2511-5（2001）.
2．Li X, Sankrithi N, Davis FC. Transforming growth factor-alpha is expressed in astrocytes of the suprachiasmatic nucleus in hamster: role of glial cells in circadian clocks. NeuroReport. 13(16):2143-7（2002）.
3．Li X, Gilbert J, Davis FC. Disruption of masking by hypothalamic lesions in Syrian hamsters. J Comp Physiol. 191(1):23-30（2005）.
4．Li X, Davis FC. Developmental expression of 3 clock genes in the Syrian hamster. Dev Brain Res.158(1-2):31-40 (2005).
5．Ding Q, Li X^*. Neural pathway for fever generation. Neurosci Bulletin. 22（6）：350-354 (2006).
6. Ji Y, Li X*. Cloning and developmental expression analysis of PK2 and PKR2 in the suprachiasmatic nucleus of the Syrian hamster. Brain Res. 1271: 18-26 (2009).

7. Yoshida K, Li X, Cano G, Lazarus M,Saper CB. Parallel preoptic pathways for the inhibition of thermogenesis. J Neurosci. 29(38):11954-64 (2009).

8. Ji Y, Qin Y, Shu HB, Li X. Methylation analyses on promoters of mPer1, mPer2 and mCry1 during perinatal development. Biochem Biophys Res Commun. 391(4): 1742-7 (2010).

9.Li C, Yu S, Zhong X, Wu J, Li X. Circadian Rhythms of Fetal Liver Transcription Persist in the Absence of Canonical Circadian Clock Gene Expression Rhythms in vivo. PLoS One. 7(2): e30781 (2012).

10. Li C, Yu S, Zhong X, Wu J, Li X. Transcriptome Comparison between Fetal and Adult Mouse Livers: Implications for Circadian Clock Mechanisms. PLoS One. 7(2): e31292 (2012).

11. Li C, Gong C, Yu S, Wu J, Li X. Epigenetic control of circadian clock operation during development. Genetics Res International 845429 (2012).

12. Li X, Li C, Gong C, Yu S. Epigenetic Control of Circadian Clock Operation. In “DNA methylation: principles, mechanisms and challenges”. Nova Science Pub Inc.(2013).

13. Wu S, Lv Z, Zhu J, Dong P, Zhou F, Li X, Cai Z. Somatic mutation of the androgen receptor gene is not associated with transitional cell carcinoma: a “negative” study by whole-exome sequencing analysis. Eur Urol. 64(6): 1018-9 (2013).

14. Avp-iCre转基因小鼠的鉴定。 李娟(#); 李晓东(*)湖北师范学院学报(自然科学版), 2015.6.25, (02): 39-43。

15.视交叉上核在昼夜节律中的作用。 程满,余爽,李娟,李晓东。《生命科学》2015年11期。

16. Gong C, Li C, Qi X, Song Z, Wu J, Hughes, ME, Li X. The daily rhythms of mitochondrial gene expression and oxidative stress regulation are altered by aging in the mouse liver. Chronobiol Int.32(9):1254-63 (2015).

17. Hughes ME, Abruzzi KC, Allada R, Anafi R, Arpat AB, Asher G, Baldi P, de Bekker C, Bell-Pedersen D, Blau J, Brown S, Ceriani MF, Chen Z, Chiu JC, Cox J, Crowell AM, DeBruyne JP, Dijk DJ, DiTacchio L, Doyle FJ, Duffield GE, Dunlap JC, Eckel-Mahan K, Esser KA, FitzGerald GA, Forger DB, Francey LJ, Fu YH, Gachon F, Gatfield D, de Goede P, Golden SS, Green C, Harer J, Harmer S, Haspel J, Hastings MH, Herzel H, Herzog ED, Hoffmann C, Hong C, Hughey JJ, Hurley JM, de la Iglesia HO, Johnson C, Kay SA, Koike N, Kornacker K, Kramer A, Lamia K, Leise T, Lewis SA, Li J, Li X, Liu AC, Loros JJ, Martino TA, Menet JS, Merrow M, Millar AJ, Mockler T, Naef F, Nagoshi E, Nitabach MN, Olmedo M, Nusinow DA, Ptáček LJ, Rand D, Reddy AB, Robles MS, Roenneberg T, Rosbash M, Ruben MD, Rund SSC, Sancar A, Sassone-Corsi P, Sehgal A, Sherrill-Mix S, Skene DJ, Storch KF, Takahashi JS, Ueda HR, Wang H, Weitz C, Westermark PO, Wijnen H, Xu Y, Wu G, Yoo SH, Young M, Zhang EE, Zielinski T, Hogenesch JB. Guidelines for Genome-Scale Analysis of Biological Rhythms. J Biol Rhythms.

32(5):380-393 (2017).

18. Zhu J, Li C, Gong C, Li X. Regulation of Pol II Pausing Is Involved in Daily Gene Transcription in the Mouse Liver. J Biol Rhythms. 33(4):350-362 (2018).

Fundings：
1.Distinguished Young Scientist Fund, Hubei Province (PI）.
2.NSFC30700212(PI，2008/1-2010/12）.
3.State Key Research Project: “Establishment and Application of Mouse Models for Human diseases”（participating）.
4.China MOE New Scholar Fund（PI，2008/1-2009/12）.

5. NSFC Key project 30830112 （2009/1-2012/12）（participating）.

6.China MOST Key Research Project: “Proteomics and Peptidomics Research on Depression(2009/1-2012/12, participating）.

7. NSFC30700212（PI）.

8. NSFC30970953（PI）.

9. NSFC31471124（PI）.

10. NSFC81271464（PI）.

Research

The lab in the past has focused on the neurobiological mechanism(s) underlying circadian rhythms generation at the systems neuroscience level, using mouse and Syrian hamster as experimental animals. Viral-vector mediated RNAi, tract tracing and behavioral and physiological telemetry recording techniques are applied. Cre transgenic and conditional knockout mice were also used to characterize the potential roles of different cell types in the SCN in circadian rhythm generation. We also studied the possible epigenetic mechanism(s) involved in the developmental onset of clock functions in central and peripheral oscillators, with an initial focus on promoter DNA methylation of clock genes.

The lab is currently investigating two fundamental questions in circadian rhythm research using mouse liver as the experimental model.

1. Transcriptional basis of circadian rhythm generation.

The circadian clock orchestrates gene expression rhythms. Regulation at the level of gene transcription is essential for molecular and cellular rhythms. We recently performed Pol II ChIP-seq across the day in the mouse liver, and quantitatively analyzed binding signals within the transcription start site (TSS) region and the gene body. We frequently found discordant changes between Pol II near the TSS ([Pol II]_TSS, paused Pol II) and that within the gene body ([Pol II]_GB, transcribing Pol II) across the genome, with only [Pol II]_GB always reflecting transcription of clock and clock-controlled genes. Pol II traveling ratios of more than 7000 genes showed significant daily changes (> 1.5 fold). Therefore, there is widespread regulation of Pol II pausing in the mouse liver. Interestingly, gene transcription rhythms exhibited a bimodal phase distribution, peaking near ZT0 and ZT12, respectively, while a genomewide increase in [Pol II]_TSS and TR was found near ZT0. ChIP-seq against Tbp, a pre-initiation complex (PIC) component, revealed that Pol II recruitment mainly played an indirect role in transcriptional output, with transcriptional termination and pause release functioning prominently in determining the fate of initiated Pol II and its pausing status. We are currently investigating on the critical, albeit complex role of Pol II pausing control in regulating the temporal output of gene transcription, as well as how the global pattern of pausing regulation is established.

2. Mechanism(s) for the disruption of mitochondrial rhythms in livers of old mice.

Mitochondria play essential roles in metabolism, and are the major sites of reactive oxygen species (ROS) production in the cell. Previously, it was shown that the clock regulates mitochondrial functions via driving daily changes in mitochondrial NAD⁺ level and Sirt3 activity. We recently found that, besides this control route, the expression of some mitochondrial genes and the regulation of mitochondrial oxidative stress were also rhythmic in the liver. Because those rhythms were altered by the Clock^Δ19 mutation in young mice, a role of the clock in regulating those rhythms was suggested. However, the expression rhythms of some mitochondrial genes in the liver were altered during aging, and the temporal regulation over the dynamics of mitochondrial oxidative stress was disrupted, despite normal expression of clock genes. Our results thus suggested that mitochondrial functions are combinatorily regulated by the clock and age-dependent mechanism(s), and aging disrupts mitochondrial rhythms through mechanisms downstream of the clock. Currently, we are using RNA-seq and ChIP-seq and metabolic monitoring to systematically

characterize the mechanisms for altered mitochondrial gene expression and functions during aging.