季斌

放射药学与分子影像学中心, 研究员，博士生导师

姓名	季斌	性别	男
职称	研究员	学位	博士
电话		传真
电子邮件	binji@fudan.edu.cn	个人主页
通讯地址	上海市浦东新区张衡路826号复旦大学药学院

教育经历

1989.09 – 1993.07 上海医科大学药学院，药学专业，学士
1998.04 – 2000.03 日本国立大学千叶大学药学部，临床药学专业，硕士
2000.04 – 2003.03 日本国立大学千叶大学药学部，临床药学专业，博士

工作经历

2003.04 – 2005.03 日本量子科学技术研究开发机构脑功能影像研究部，博士后

2005.04 – 2021.03 日本量子科学技术研究开发机构脑功能影像研究部，主任研究员

2021.04 – 至今复旦大学药学院，研究员

承担科研项目情况

获奖及荣誉

研究方向

1. 开发中枢神经系统疾病（阿尔兹海默病，帕金森综合症，癫痫），肾脏疾病（糖尿病肾病）和肿瘤（乳腺癌）的PET/SPECT/MRI分子探针

2. 利用PET/SPECT/MRI分子探针探讨上述疾病的发生发展的机理机制

主要学术贡献

1. 开发具有临床应用价值的PET/SPECT的分子探针。现已开发成功1. 用于探测阿尔茨海默氏症（AD）的2大病理b-amyloid(Ab)和tau的SPECT用探针AD-DRK（已获得日本专利授权） 2. 用于探测化学遗传学工具DREADD的PET用探针。研究成果发表在核心期刊Nature Neuroscience （2020）,Nature Communications （2016）, the Journal of Neuroscience （2016），Nature Neuroscience （2015）上）。3.用于在体检测认知症患者脑内tau积累的PET探针¹¹C-PBB3的开发（研究成果发表在神经科学的核心期刊Neuron(2013)，Brain(2017)和核医学的核心期刊Journal of Nuclear Medicine(2018)上)。¹¹C-PBB3的后续产品¹⁸F-PMPBB3正在日本和中国同时进行临床研究。

2. 探讨动物模型（特别是AD以及其他的tauopathy等认知症）和患者的病理特点。了解各种动物模型和患者之间病变的区别。这对于药物开发以及发病机理的研究中如何选择合适的动物模型十分重要。通过比较了几种比较常用的AD动物模型和AD患者的脑标本后发现尽管b-amyloid(Ab)的表达没有大的区别，但是Ab聚集后产生的脑内老人斑（senile plaque）却有很大的区别。Amyloid的分子探针更容易检测出AD患者和APP23模型鼠脑内的老人斑。在开发Amyloid的分子探针时APP23模型鼠才是理想的AD动物模型（研究成果发表在the Journal of Neuroscience（2007）上）。另外，和APP23模型鼠相比，在tauopathy的动物模型PS19模型鼠脑中，活化型microglia有着更高的TSPO表达, 这点更像AD患者的脑。这建议在探讨神经炎症时，PS19模型鼠是更好的动物模型（研究成果发表在the Journal of Neuroscience（2011）上）。在此基础上，开发了一个经鼻给药的tau疫苗（已获得日本和美国专利授权）来治疗PS19小鼠的神经机能障碍，并利用分子影像技术在体跟踪PS19小鼠的脑萎缩和神经炎症。发现tau疫苗能有效地改善PS19小鼠的脑萎缩和神经机能，为利用tau疫苗来治疗tauopathy疾病提供了实验证据。并且显示了利用分子影像技术跟踪活体动物模型脑内病理变化在新药开发及循证医学中的巨大的利用价值。研究成果发表在Nature集团出版社的杂志NPJ Vaccines（2020））

3. 开发分子影像生物标志物。通过开发神经炎症的生物标志物TSPO的免疫染色用的高特异性抗体，发现了在脑内，TSPO在能伤害神经细胞的活性化microglia和在能保护神经细胞的活性化astrocyte中都能高表达。这样使用TSPO的分子探针虽然能间接的探测到受损的神经细胞，却无法区别活性化microglia和活性化astrocyte。揭示了开发新的神经炎症生物标志物以及相应的分子探针的必要性（研究成果发表在神经科学的核心期刊the Journal ofNeuroscience(2008)上）。开发的TSPO抗体受到了世界上研究者的欢迎，有超过20个的实验室在使用该TSPO抗体。

代表性论文及专利

1. Zhou, X. Y., Ji, B.(Co-first author), Seki, C., Nagai, Y., Minamimoto, T., Fujinaga, M., Zhang, M. R., Saito, T., Saido, T. C., Suhara, T., Kimura, Y., and Higuchi, M. PET imaging of colony-stimulating factor 1 receptor: a head-to-head comparison of a novel radioligand, 11C-GW2580, and 11C-CPPC, in mouse models of acute and chronic neuroinflammation and a rhesus monkey. J Cereb Blood Flow Metab (in press)
2.Maeda, J., Minamihisamatsu, T., Shimojo, M., Ono, M., Minatohara, K., Takuwa, H., Takado, Y., Ji, B., Zhang, M. R., Suhara, T., Sahara, N., and Higuchi, M. Distinct microglial response against Alzheimer’s pathologies characterized by P2Y12 receptor. Brain Communications (in press)
3.Ji, B.*, Ono, M., Yamasaki, T., Fujinaga, M., Zhang, M. R., Seki, C., Aoki, I., Kito, S., Sawada, M., Suhara, T., Sahara, N., and Higuchi, M. Detection of Alzheimer’s Disease-related Neuroinflammation by a PET Ligand Selective for Glial Versus Vascular Translocator Protein. J Cereb Blood Flow Metab 0, 1-14
4.Tanimoto, Y., Yamasaki, T., Nagoshi, N., Nishiyama, Y., Nori, S., Nishimura, S., Iida, T., Ozaki, M., Tsuji, O., Ji, B., Aoki, I., Jinzaki, M., Matsumoto, M., Fujibayashi, Y., Zhang, M. R., Nakamura, M., and Okano, H. (2020) In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation. Stem Cells Translational Medicine 9, 465-477
5.Takeuchi, H., Imamura, K., Ji, B., Tsukita, K., Enami, T., Takao, K., Miyakawa, T., Hasegawa, M., Sahara, N., Iwata, N., Inoue, M., Hara, H., Tabira, T., Ono, M., Trojanowski, J. Q., Lee, V. M., Takahashi, R., Suhara, T., Higuchi, M., and Inoue, H. (2020) Nasal vaccine delivery attenuates brain pathology and cognitive impairment in tauopathy model mice. NPJ vaccines 5, 28
6.Nagai, Y., Miyakawa, N., Takuwa, H., Hori, Y., Oyama, K., Ji, B., Takahashi, M., Huang, X. P., Slocum, S. T., DiBerto, J. F., Xiong, Y., Urushihata, T., Hirabayashi, T., Fujimoto, A., Mimura, K., English, J. G., Liu, J., Inoue, K. I., Kumata, K., Seki, C., Ono, M., Shimojo, M., Zhang, M. R., Tomita, Y., Nakahara, J., Suhara, T., Takada, M., Higuchi, M., Jin, J., Roth, B. L., and Minamimoto, T. (2020) Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys. Nat Neurosci 23, 1157-1167
7.Barron, A. M., Ji, B., Fujinaga, M., Zhang, M. R., Suhara, T., Sahara, N., Aoki, I., Tsukada, H., and Higuchi, M. (2020) In vivo positron emission tomography imaging of mitochondrial abnormalities in a mouse model of tauopathy. Neurobiology of Aging 94, 140-148
8.Barron, A. M., Higuchi, M., Hattori, S., Kito, S., Suhara, T., and Ji, B.* (2020) Regulation of Anxiety and Depression by Mitochondrial Translocator Protein-Mediated Steroidogenesis: the Role of Neurons. Molecular Neurobiology
9.Lu, Y., Guo, Z., Zhang, Y., Li, C., Zhang, Y., Guo, Q., Chen, Q., Chen, X., He, X., Liu, L., Ruan, C., Sun, T., Ji, B., Lu, W., and Jiang, C. (2019) Microenvironment Remodeling Micelles for Alzheimer's Disease Therapy by Early Modulation of Activated Microglia. Advanced Science 6, 1801586
10.Ni, R., Ji, B.*, Ono, M., Sahara, N., Zhang, M. R., Aoki, I., Nordberg, A., Suhara, T., and Higuchi, M. (2018) Comparative In Vitro and In Vivo Quantifications of Pathologic Tau Deposits and Their Association with Neurodegeneration in Tauopathy Mouse Models. Journal of Nuclear Medicine : 59, 960-966
11.Ishikawa, A., Tokunaga, M., Maeda, J., Minamihisamatsu, T., Shimojo, M., Takuwa, H., Ono, M., Ni, R., Hirano, S., Kuwabara, S., Ji, B., Zhang, M. R., Aoki, I., Suhara, T., Higuchi, M., and Sahara, N. (2018) In Vivo Visualization of Tau Accumulation, Microglial Activation, and Brain Atrophy in a Mouse Model of Tauopathy rTg4510. J Alzheimers Dis 61, 1037-1052
12.Barron, A. M., Ji, B.*, Kito, S., Suhara, T., and Higuchi, M. (2018) Steroidogenic abnormalities in translocator protein knockout mice and significance in the aging male. Biochem J 475, 75-85
13.Ono, M., Sahara, N., Kumata, K., Ji, B., Ni, R., Koga, S., Dickson, D. W., Trojanowski, J. Q., Lee, V. M., Yoshida, M., Hozumi, I., Yoshiyama, Y., van Swieten, J. C., Nordberg, A., Suhara, T., Zhang, M. R., and Higuchi, M. (2017) Distinct binding of PET ligands PBB3 and AV-1451 to tau fibril strains in neurodegenerative tauopathies. Brain 140, 764-780
14.Nagai, Y., Kikuchi, E., Lerchner, W., Inoue, K. I., Ji, B., Eldridge, M. A., Kaneko, H., Kimura, Y., Oh-Nishi, A., Hori, Y., Kato, Y., Hirabayashi, T., Fujimoto, A., Kumata, K., Zhang, M. R., Aoki, I., Suhara, T., Higuchi, M., Takada, M., Richmond, B. J., and Minamimoto, T. (2016) PET imaging-guided chemogenetic silencing reveals a critical role of primate rostromedial caudate in reward evaluation. Nat Commun 7, 13605
15.Liu, Y., An, S., Li, J., Kuang, Y., He, X., Guo, Y., Ma, H., Zhang, Y., Ji, B., and Jiang, C. (2016) Brain-targeted co-delivery of therapeutic gene and peptide by multifunctional nanoparticles in Alzheimer's disease mice. Biomaterials 80, 33-45
16.Ji, B., Kaneko, H., Minamimoto, T., Inoue, H., Takeuchi, H., Kumata, K., Zhang, M. R., Aoki, I., Seki, C., Ono, M., Tokunaga, M., Tsukamoto, S., Tanabe, K., Shin, R. M., Minamihisamatsu, T., Kito, S., Richmond, B. J., Suhara, T., and Higuchi, M. (2016) Multimodal Imaging for DREADD-Expressing Neurons in Living Brain and Their Application to Implantation of iPSC-Derived Neural Progenitors. The Journal of Neuroscience 36, 11544-11558
17.Higuchi, M., B., J., Maeda, J., Sahara, N., and Suhara, T. (2016) In vivo imaging of neuroinflammation in Alzheimer’s disease. Clinical & Experimental Neuroimmunology 7, 139-144
18.Eldridge, M. A., Lerchner, W., Saunders, R. C., Kaneko, H., Krausz, K. W., Gonzalez, F. J., Ji, B., Higuchi, M., Minamimoto, T., and Richmond, B. J. (2016) Chemogenetic disconnection of monkey orbitofrontal and rhinal cortex reversibly disrupts reward value. Nat Neurosci 19, 37-39
19.Barron, A. M., Tokunaga, M., Zhang, M. R., Ji, B., Suhara, T., and Higuchi, M. (2016) Assessment of neuroinflammation in a mouse model of obesity and beta-amyloidosis using PET. J Neuroinflammation 13, 221
20.Tiwari, A. K., Ji, B.(co-first author), Yui, J., Fujinaga, M., Yamasaki, T., Xie, L., Luo, R., Shimoda, Y., Kumata, K., Zhang, Y., Hatori, A., Maeda, J., Higuchi, M., Wang, F., and Zhang, M. R. (2015) [18F]FEBMP: Positron Emission Tomography Imaging of TSPO in a Model of Neuroinflammation in Rats, and in vitro Autoradiograms of the Human Brain. Theranostics 5, 961-969
21.Ji, B.*, Chen, C. J., Bando, K., Ashino, H., Shiraishi, H., Sano, H., Kasahara, H., Minamizawa, T., Yamada, K., Ono, M., Zhang, M. R., Seki, C., Farde, L., Suhara, T., and Higuchi, M. (2015) Distinct binding of amyloid imaging ligands to unique amyloid-beta deposited in the presubiculum of Alzheimer's disease. Journal of Neurochemistry 135, 859-866
22.Chen, C. J., Bando, K., Ashino, H., Taguchi, K., Shiraishi, H., Shima, K., Fujimoto, O., Kitamura, C., Matsushima, S., Uchida, K., Nakahara, Y., Kasahara, H., Minamizawa, T., Jiang, C., Zhang, M. R., Ono, M., Tokunaga, M., Suhara, T., Higuchi, M., Yamada, K., and Ji, B. *(2015) In vivo SPECT imaging of amyloid-beta deposition with radioiodinated imidazo[1,2-a]pyridine derivative DRM106 in a mouse model of Alzheimer's disease. Journal of Nuclear Medicine 56, 120-126