夏軍

香港科技大學理學院生物化學系副教授，浙江大學醫學院客座教授。2001於約翰·霍普金斯大學獲得博士學位，師從Richard L. Huganir教授，主要從事神經突觸轉導、男性不育的病因學研究，以及學習與記憶的分子機制研究。

Globozoospermia（圓頭精子症，又名round-headed spermatozoa）是一種以精子頂體異常為主要特徵的不育綜合症，是一種罕見的不育疾病。夏軍教授以及其香港科技大學的同事在一項新的研究中以雄性小鼠為研究模型，找出一種與不育有關的蛋白，PICK1，深入研究發現缺乏PICK1的雄性小鼠其臨床上的表徵與人類男性圓頭精子症類似，這一結果可能對研究人類男性圓頭精子症有借鑒意義。

在小鼠模型中，缺乏PICK1蛋白會導致精子計數低，並且有限的精子異型（圓頭），導致精子的遊動能力受到極大的破壞。對這些異常的精子進行深入研究發現，精子的頂體發生畸變，正常來說頂體中含有特殊的蛋白能幫助精子穿透卵子的外層達到受精的作用。研究發現PICK1與頂體細胞結構中的另外兩種蛋白有密切的聯繫，分別是GOPC和CK2-alpha。

這些結果表明，PICK1蛋白是促進精子頂體發育的關鍵蛋白，缺失PICK1蛋白將導致精子受破壞，失去活動能力和受精能力。這一研究成果可能對男性不育的治療有新的意義。

2008年首屆東南亞高等教育協會—史高柏年輕科學家獎

1. Xu, J., Xiao, N., Xia, J.(2010). Thrombospondin 1 Accelerates Synaptogenesis in Hippocampal Neurons through Neuroligin 1. Nat. Neurosci. 13 (1): 22-4 .

2. Xiao, N., Kam, C., Shen, C., Jin, W., Wang, J., Lee, K.M., Jiang, L., and Xia, J.(2009). PICK1 deficiency causes male infertility in mice by disrupting acrosome formation. J. Clin. Invest.119(4): 802-812.

3. Cao, M., Xu, J., Shen, C., Kam, C., Huganir, R.L., and Xia, J.(2007). PICK1-ICA69 heteromeric BAR domain complex regulates synaptic targeting and surface expression of AMPA receptors. J. Neurosci.27(47): 12945-12956 .

4. Pan, L., Wu, H., Shen, C., Shi, Y., Jin, W., Xia, J.,*and Zhang, M.* (2007). Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes. EMBO J. 26(21): 4576-87 . * Co-corresponding authors.

5. Jin, W., Ge, W., Xu, J., Cao, M., Peng, L., Yung, W., Liao, D., Duan, S., Zhang, M., and Xia, J. (2006). Lipid binding regulates PICK1’s synaptic targeting, AMPA receptor trafficking and synaptic plasticity. J. Neurosci.26(9): 2380-2390.

6. Steinberg, J.P., Takamiya, K., Shen, Y., Xia, J.,Rubio, M.E., Yu, S., Jin, W., Thomas, G.M., Linden, D.J., and Huganir, R.L. (2006). Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1Eliminate Cerebellar long-term depression. Neuron 49(6): 845-860.

7. Gardner, S.M., Takamiya, K., Xia, J., Suh, J., Johnson, R., Yu, S., and Huganir, R.L. (2005). Calcium-Permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF. Neuron45(6): 903-915.

8. Long, J.F., Feng, W., Wang, R., Chan, L.N., Ip, F.C., Xia, J., Ip, N.Y., and Zhang, M. (2005). Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem. Nat. Struct. Mol. Biol.12(8): 722-8.

9. Xia, J., Chung, H.J., Wihler, C., Huganir, R.L., and Linden, D.J. (2000). Cerebellar long-term depression requires PKC regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron.28(2): 499-510.

10. Xia, J., Zhang, X., Staudinger, J., and Huganir, R.L. (1999). Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron. 22(1): 179-87.