Male infertility is an important disease that threatens human health. Our group systematically studied the pathogenesis of male infertility related to spermiogenesis, meiosis and somatic-germ cell interaction with multiple approaches. Recently, we have made a series of accomplishments in these fileds, which not only provide new insight into the regulation of gametogenesis but also might provide new way of diagnosis and even the therapy of human sterility and reproductive related diseases. For example, our studies revealed that SUN5 and PMFBP1 are essential for the integration of the sperm head to the tail, confirming that SUN5 and PMFBP1 are the main causes of the acephalic spermatozoa syndrome. We also showed that RNF20-mediated H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation and suggest an old drug may provide a new way to treat some oligoor azoospermia patients with chromatin relaxation disorders.

“To be or not to be” is the eternal theme for all creatures. Thus, reproduction and aging are the most fundamental issues of biology. According to my research experience, our long-term goal is to study the general mechanisms of protein modification and their roles in reproduction and aging.

In the immediate future, we would like to address the following questions:

1. Posttranslational modification regulation of gametogenesis, especially for meiosis.

2. The functional role of histone modifications on meiosis, stem cell reprogramming, self-renew and differentiation.

3. Posttranslational regulation basis of reproductive and aging related diseases.

Selected Publications

1. Gao F^#, Li G^#, Liu C^#, Gao H^#, Wang H, Liu W, Chen M, Shang Y, Wang L, Shi J, Xia W, Jiao J, Gao F, Li J, Chen L^*, Li W^*. (2018). Autophagy regulates testosterone synthesis by facilitating cholesterol uptake in the Leydig cells. J Cell Biol. 217(6).

2. Wang L^#, Tu Z^#, Liu C^#, Liu H, Kaldis P, Chen Z^*, Li W^*. (2018). Dual roles of TRF1 in tethering telomeres to the nuclear envelope and protecting them from fusion during meiosis. Cell Death Differ. 25:1174-1188.

3. Shang Y, Zhu F, Wang L, Ouyang YC, Dong MZ, Liu C, Zhao H, Cui X, Ma D, Zhang Z, Yang X, Guo Y, Liu F, Yuan L, Gao F^*, Guo X^*, Sun QY^*, Cao Y^*, Li W^*. (2017). Essential role for SUN5 in anchoring sperm head to the tail. Elife. 6:e28199.

4. Liu C, Liu W, Ye Y, Li W^*. (2017). Ufd2p synthesizes branched ubiquitin chains to promote the degradation of proteins modified with atypical ubiquitin chains. Nat Commun. 8:14274.

5. Xu Z, Song Z, Li G, Tu H, Liu W, Liu Y, Wang P, Wang Y, Cui X, Liu C, Shang Y, de Rooij DG, Gao F, Li W^*. (2016). H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation. Nucleic Acids Res. 44(20):9681-9697.

6. Shang YL, Wang HN, Jia PF, Zhao HC, Liu C, Liu WX, Song ZH, Xu ZL, Yang L, Wang YF, Li W^*. (2016). Autophagy regulates spermatid differentiation via degradation of PDLIM1. Autophagy. 12(9):1575-1592.

7. Wen FP, Guo YS, Hu Y, Wang YT, Wang Q, Yu HY, Tang CM, Yang J, Zhou T, Sha JH, Guo XJ^*, Li W^*. (2016). Distinct temporal requirements for autophagy and proteasome in yeast meiosis. Autophagy. 12(4):671-688.

8. Liu C，Wang HN, Shang YL, Liu WX, Song ZH, Zhao HC, Wang LN, Jia PF, Gao FY, Xu ZL, Yang L, Gao F, Li W^*. (2016). Autophagy is required for ectoplasmic specialization assembly in Sertoli cells. Autophagy. 12(5):814-832.

9. Wang HN, Wan HF, Li XX, Liu WX, Chen Q, Wang YQ, Yang L, Duan EK, Tang HM, Zhang XJ, Zhao XY, Gao F^*, Li W^*. (2014). Atg7 is required for acrosome biogenesis during spermatogenesis in mice. Cell Res. 24(7):852-869.

10. Liu WX, Shang YL, Zeng Y, Liu C, Li YC, Zhai LH, Wang P, Lou JZ, Xu P, Ye Y^*, Li W^*. (2014). Dimeric Ube2g2 simultaneously engages donor and acceptor ubiquitins to form Lys48-linked ubiquitin chains. EMBO J. 33(1):46-61.

11. Li W^#, Tu D^#, Li LY, Wollert T, Ghirlando R, Brunger AT, Ye Y. (2009). Mechanism of ubiquitin chain assembly on the active site cysteine of the ubiquitin conjugating enzyme Ube2g2. Proc Natl Acad Sci U S A. 106(10):3722-3727.

12. Li W, Tu D, Brunger A, Ye Y. (2007). An ubiquitin ligase transfers preformed polyqubiquitin chains from a conjugating enzyme to substrate. Nature. 446(7133):333-337.