郑红花 教授/博导 研究方向：小胶质细胞与衰老和神经退行性变 所在系部：基础医学部/神经科学研究所 办公电话：0592-2880582 邮 箱：honghua@xmu.edu.cn 系部网址：http://neuro.xmu.edu.cn/ |  |
研究领域
小胶质细胞（Microglia）是中枢神经系统（Central Nervous System，CNS）内特有的免疫效应细胞，大约占成年脑细胞群的5%～10%，占胶质细胞总数的10%～20%。课题组多年来致力于研究中枢神经系统中小胶质细胞上特异性表达的集落刺激因子1受体（CSF1R）导致神经退行性疾病发生的分子机制，并寻找预防和治疗策略。目前实验室主要研究工作包括：1. 揭示CSF1R生理切割产物的生理功能和生物学意义；2. 阐明CSF1R突变或功能异常参与神经退行性疾病发生的分子机制；3. 探索调控小胶质细胞功能的神经系统疾病防治靶点。主持4项国家自然科学基金项目和7项省厅级自然科学基金项目。在Cell Rep Med，Sci Transl Med，Ann Neurol，J Neurosci，FASEB J等SCI杂志上发表四十余篇研究论文，授权国家专利2项。热忱欢迎感兴趣的本科生、研究生和博士后加入本课题组。
学习经历
1993.09~1998.06 湖北省咸宁医学院临床医学专业 医学学士；
2002.09~2005.12 华中科技大学同济医学院生物化学与分子生物学专业 理学硕士；
2006.09~2009.07 华中科技大学同济医学院人体解剖与组织胚胎学专业 医学博士；
2013.09~2014.10美国Mayo Clinic神经科学 博士后
工作经历
1998.09~2009.07 历任湖北省咸宁医学院助教、讲师；
2009.08~2012.07 厦门大学医学院 助理教授；
2012.08~2020.07 厦门大学医学院 副教授；
2020.08~至今 厦门大学医学院 教授
代表性成果（近五年）
1.Li X, Hu B, Wu C, Wang Z, Fan H, Guan X, Xie S, Chen D, Huang X, Sun H, Li Y, Zhang X, Bu G, Wang Z, Zhang YW*, Zhong L*, Zhang Z*, Zheng H*. A strategy of microglia replacement alleviates microgliopathy in a CSF1R I794T hotspot mutation mouse model of CSF1R-related disorder. Cell Rep Med. 2026 Feb 27 DOI: 10.1016/j.xcrm.2026.102641
2.Zhou Y, Hu B, Luo J, Wang X, Huang X, Li Y, Zhang X, Bu G, Zhang H, Zhang YW*, Zheng H*. Soluble CSF1R alleviates microgliopathy in a CSF1R-related leukoencephalopathy (CRL) mouse model. J Neuroinflammation. 2025 Dec 5; 23(1):12. DOI: 10.1186/s12974-025-03648-4
3.Chen D, Wang C, Chen X, Li J, Chen S, Li Y, Ma F, Li T, Zou M, Li X, Huang X, Zhang YW, Zhao Y, Bu G, Zheng H*, Chen XF*, Zhang J*, Zhong L*. Brain-wide microglia replacement using a nonconditioning strategy ameliorates pathology in mouse models of neurological disorders. Sci Transl Med. 2025 Apr 30;17(796):eads6111.
4.Hu B, Zhou Y, Wu C, Xiao N, Li J, Li X, Li Y, Zhang X, Huang X, Song Y, Wang Z, Zhang YW*, Zhang Z*, Zheng H*. Evaluation of Soluble Colony Stimulating Factor 1 Receptor (CSF1R) in Peripheral Blood as a Diagnostic Marker of CSF1R-Related Disorder (CSF1R-RD) in a Murine Model and CSF1R-RD Patients. Ann Neurol. 2025 Feb;97(2):397-403.
5. Li X, Hu B, Guan X, Wang Z, Zhou Y, Sun H, Zhang X, Li Y, Huang X, Zhao Y, Wang X, Xu H, Zhang YW, Wang Z*, Zheng H*. Minocycline protects against microgliopathy in a Csf1r haplo-insufficient mouse model of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). J Neuroinflammation. 2023 May 31;20(1):134.
主持过的重要课题
1.国家自然科学基金面上项目，NO. 82271219，CSF1R突变导致认知功能损害的分子机制，52万元，2023/01-2026/12，在研，主持。
2.国家自然科学基金重大研究计划培育项目，NO. 91949129，小胶质细胞介导的天然免疫在脑衰老和神经退行性变中的作用，2020/01-2022/12，已结题，主持。
3.国家自然科学基金面上项目，NO.81771164，TREM2的功能效应及其突变体参与阿尔茨海默病发生的分子机制研究， 2018/01-2021/12，已结题，主持。
4.国家自然科学基金青年基金项目，NO. 81100842，Menin通过IGFs信号通路调控胚胎神经系统发育的组蛋白甲基化修饰机制，2012/01-2014/12，已结题，主持；
5.福建省自然科学基金面上项目，NO. 2020J01014，TREM2与CSF1R相互作用介导的小胶质细胞存活状态参与AD进程的机制，2020/11-2023/11，已结题，主持。
6.福建省高校青年自然基金重点项目（福建省教育厅科技项目），NO.JZ160403，TREM2调控小胶质细胞迁移和吞噬功能的分子机制， 2017/01-2019/12，已结题，主持。
7.福建省自然科学基金项目，NO.2016J01411，TREM2介导的小胶质细胞功能异常在AD发病中的作用及机制， 2016/04-2019/04，已结题，主持。
8.福建省自然科学基金项目，NO.2012J01418，神经管缺陷形成中Men1调控靶基因转录的机制，2012/01-2014/12，已结题，主持。
9.广东省自然科学基金项目，NO.2017A030313604，TREM2调控阿尔茨海默病（AD）病程中小胶质细胞对淀粉样斑清除功能的分子机制， 2017/05-2020/05，已结题，主持。
10.广东省自然科学基金项目，NO. 2016A030313821，miRNAs及其靶基因网络调控癫痫神经元异常放电的分子机制， 2016/06-2019/06，已结题，主持。
11. 横向课题（厦门大学附属妇女儿童医院合作课题），NO. XDHT2020366A，有机酸血症相关性疾病早期快速诊断技术体系研究及其在临床诊疗中的应用，4.5万元，2020/09-2021/03，已结题，主持。
12. 横向课题（复旦大学附属中山医院厦门医院合作课题），校合20243160A0125，《TPPU抗癫痫作用的机制研究》，11万元，2024-2025，已结题，主持。
已申请的专利
1.郑红花，郑维红，唐荣，计志林，张云武。microRNA219在制备抗癫痫药物中的应用。专利号ZL2014 1 0011211.5； 专利授权日期：2016年1月13日。
2.金光辉，张秀丽，朱铉，刘祖国，郑红花。人纤溶酶原Kringle 5短肽、其药物组合物、用途和编码该短肽的多核苷酸。专利号ZL 201010179925.9；专利授权日期：2014年5月28日
获奖情况
1. 2025年指导本科生（张乘嘉、马加良、吴歆若、蔡怀乐、余晗羽）参加“第十一届全国大学生基础医学创新论坛暨实验设计大赛”获得中南赛区（复赛）一等奖，总决赛银奖；
2. 2024年指导本科生（赵睿霖、原朴、李梦雅、邓哲）参加“第十届全国大学生基础医学创新论坛暨实验设计大赛”获得中南赛区（复赛）一等奖，总决赛铜奖；
3. 2023年指导本科生（罗奥翔、安熙怡、余高毅、赵睿霖、杨琪翔）参加“第九届全国大学生基础医学创新论坛暨实验设计大赛”获得中南赛区（复赛）一等奖，总决赛银奖；
4. 2022年指导本科生（刘桂杉、郭翰翔、冯于崇）参加“第八届全国大学生基础医学创新论坛暨实验设计大赛”获得中南赛区（复赛）三等奖；
5. 2020年指导本科生（马蒙慧、林晟、魏玥）参加“第六届全国大学生基础医学创新论坛暨实验设计大赛”获得国家级二等奖；
6. 2018年指导本科生（阮泽松、金兆星、姬翔）参加“第五届全国大学生基础医学创新论坛暨实验设计大赛”获得国家级一等奖；
7. 微课作品“肥从口入——物质代谢调节与科学合理减肥”获2017年全国高校（医学类）微课教学比赛三等奖；
8. 厦门大学“2018年度本科生科创竞赛优秀指导教师暨德贞社会课堂基金优秀指导教师” ；
9. 多次获评厦门大学医学院大学生创新创业训练计划“优秀指导教师”。
所有论文列表
1.Li X, Hu B, Wu C, Wang Z, Fan H, Guan X, Xie S, Chen D, Huang X, Sun H, Li Y, Zhang X, Bu G, Wang Z, Zhang YW, Zhong L, Zhang Z, Zheng H. A strategy of microglia replacement alleviates microgliopathy in a CSF1R I794T hotspot mutation mouse model of CSF1R-related disorder. Cell Rep Med. 2026 Feb 27.
2.Zhou Y, Hu B, Luo J, Wang X, Huang X, Li Y, Zhang X, Bu G, Zhang H, Zhang YW*, Zheng H. Soluble CSF1R alleviates microgliopathy in a CSF1R-related leukoencephalopathy (CRL) mouse model. J Neuroinflammation. 2025 Dec 5; 23(1):12.
3.Chen D, Wang C, Chen X, Li J, Chen S, Li Y, Ma F, Li T, Zou M, Li X, Huang X, Zhang YW, Zhao Y, Bu G, Zheng H*, Chen XF*, Zhang J*, Zhong L*. Brain-wide microglia replacement using a nonconditioning strategy ameliorates pathology in mouse models of neurological disorders. Sci Transl Med. 2025 Apr 30;17(796):eads6111.
4.Hu B, Zhou Y, Wu C, Xiao N, Li J, Li X, Li Y, Zhang X, Huang X, Song Y, Wang Z, Zhang YW*, Zhang Z*, Zheng H*. Evaluation of Soluble Colony Stimulating Factor 1 Receptor (CSF1R) in Peripheral Blood as a Diagnostic Marker of CSF1R-Related Disorder (CSF1R-RD) in a Murine Model and CSF1R-RD Patients. Ann Neurol. 2025 Feb;97(2):397-403.
5.Sun X, Pan S, Li D, Su M, Zheng H, Zhang YW, Li Y. Cell Adhesion Molecule Protocadherin-γC5 Ameliorates Aβ Plaque Pathogenesis by Modulating Astrocyte Function in Alzheimer's Disease. J Neurosci. 2025 Mar 5.
6.Zhang L, Huang L, Zhou Y, Meng J, Zhang L, Zhou Y, Zheng N, Guo T, Zhao S, Wang Z, Huo Y, Zhao Y, Chen XF, Zheng H, Holtzman DM, Zhang YW. Microglial CD2AP deficiency exerts protection in an Alzheimer's disease model of amyloidosis. Mol Neurodegener. 2024 Dec 18.
7. Wang N, Cai L, Pei X, Lin Z, Huang L, Liang C, Wei M, Shao L, Guo T, Huang F, Luo H, Zheng H, Chen XF, Leng L, Zhang YW, Wang X, Zhang J, Guo K, Wang Z, Zhang H, Zhao Y, Xu H. Microglial apolipoprotein E particles contribute to neuronal senescence and synaptotoxicity. iScience. 2024 May 16;27(6):110006.
8.Su M, Xuan E, Sun X, Pan G, Li D, Zheng H, Zhang YW, Li Y. Synaptic adhesion molecule protocadherin-γC5 mediates β-amyloid-induced neuronal hyperactivity and cognitive deficits in Alzheimer's disease. J Neurochem. 2024 Jun;168(6):1060-1079.
9.Li M, Hu B, Wu Z, Wang Z, Weng J, Zheng H*, Sun L*. Sporopollenin exine capsules modulate the function of microglial cells. Biomater Sci. 2024 Jan 30;12(3):710-724.
10.Li X, Hu B, Guan X, Wang Z, Zhou Y, Sun H, Zhang X, Li Y, Huang X, Zhao Y, Wang X, Xu H, Zhang YW, Wang Z*, Zheng H*. Minocycline protects against microgliopathy in a Csf1r haplo-insufficient mouse model of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). J Neuroinflammation. 2023 May 31;20(1):134.
11.Wang W, Li Y, Ma F, Sheng X, Chen K, Zhuo R, Wang C, Zheng H, Zhang YW, Bu G, Chen XF, Zhong L. Microglial repopulation reverses cognitive and synaptic deficits in an Alzheimer's disease model by restoring BDNF signaling. Brain Behav Immun. 2023 Oct;113:275-288.
12.Zhang C, Zheng H, Li X, Li S, Li W, Wang Z, Niu S, Wang X, Zhang Z. Novel mutations in HTRA1-related cerebral small vessel disease and comparison with CADASIL. Ann Clin Transl Neurol. 2022 Oct; 9(10):1586-1595.
13.Hu B, Duan S, Wang Z, Li X, Zhou Y, Zhang X, Zhang YW*, Xu H*, Zheng H*. Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders. Front Aging Neurosci. 2021 Nov 15;13:789834.
14.Lu P, Wang F, Zhou S, Huang X, Sun H, Zhang YW, Yao Y, Zheng H*. A Novel CNTNAP2 Mutation Results in Abnormal Neuronal E/I Balance. Front Neurol. 2021 Oct 19;12:712773.
15.Cheng B, Li X, Dai K, Duan S, Rong Z, Chen Y, Lü L, Liu Z, Huang X, Xu H, Zhang YW*, Zheng H*. Triggering receptor expressed on myeloid cells-2 (TREM2) interacts with colony-stimulating factor 1 receptor (CSF1R) but is not necessary for CSF1/CSF1R-mediated microglia survival. Front Immunol. 2021;12:633796.
16.Wei Y, Ma M, Lin S, Li X, Shu Y, Wang Z, Zhou Y, Hu B, Cheng B, Duan S, Huang X, Xu H, Zhang YW, Zheng H*. Proteolytic Shedding of Human Colony-Stimulating Factor 1 Receptor and its implication. J Cell Mol Med. 2021. Mar 30.
17.Liu Z, Ning J, Zheng X, Meng J, Han L, Zheng H, Zhong L, Chen XF, Zhang X, Luo H, Can D, Xu H, Zhang YW. TMEM59 interacts with TREM2 and modulates TREM2-dependent microglial activities. Cell Death Dis. 2020 Aug 13;11(8):678.
18.Rong Z, Cheng B, Zhong L, Ye X, Li X, Jia L, Li Y, Shue F, Wang N, Cheng Y, Huang X, Liu CC, Fryer JD, Wang X, Zhang YW, Zheng H*. Activation of FAK/Rac1/Cdc42-GTPase signaling ameliorates impaired microglial migration response to Aβ42 in triggering receptor expressed on myeloid cells 2 loss-of-function murine models. FASEB J. 2020; 34(8):10984-10997.
19.Lin JZ, Zheng HH, Ma QL, Wang C, Fan LP, Wu HM, Wang DN, Zhang JX, Zhan YH. Cortical Damage Associated With Cognitive and Motor Impairment in Hereditary Spastic Paraplegia: Evidence of a Novel SPAST Mutation. Front Neurol. 2020 May 27;11:399.
20.Sun L, Cheng B, Zhou Y, Fan Y, Li W, Qiu Q, Fang Y, Xiao S*, Zheng H*, Li X*. ErbB4 Mutation that Decreased NRG1-ErbB4 Signaling Involved in the Pathogenesis of Amyotrophic Lateral Sclerosis/Frontotemporal Dementia. J Alzheimers Dis. 2020 Feb 11; 74(2):535-544.
21.Zhao S, Li Z, Zhang M, Zhang L, Zheng H, Ning J, Wang Y, Wang F, Zhang X, Gan H, Wang Y, Zhang X, Luo H, Bu G, Xu H, Yao Y, Zhang YW. A brain somatic RHEB doublet mutation causes focal cortical dysplasia type II. Exp Mol Med. 2019 Jul 23; 51(7):84.
22.Fu H, Cheng Y, Luo H, Rong Z, Li Y, Lu P, Ye X, Huang W, Qi Z, Li X, Cheng B, Wang X, Yao Y, Zhang YW, Zheng W, Zheng H*. Silencing MicroRNA-155 Attenuates Kainic Acid-Induced Seizure by Inhibiting Microglia Activation. Neuroimmunomodulation. 2019 Mar 29:1-10.
23.Zheng H*, Cheng B, Li Y, Li X, Chen X, Zhang YW*. TREM2 in Alzheimer's Disease: Microglial Survival and Energy Metabolism. Front Aging Neurosci. 2018 Nov 23;10:395.
24.Zhuang K, Huang C, Leng L, Zheng H, Gao Y, Chen G, Ji Z, Sun H, Hu Y, Wu D, Shi M, Li H, Zhao Y, Zhang Y, Xue M, Bu G, Huang TY, Xu H, Zhang J*. Neuron-specific menin deletion leads to synaptic dysfunction and cognitive impairment by modulating p35 expression. 2018; Cell reports. 2018 Jul 17; 24(3):701-712.
25.Ye X, Rong Z, Li Y, Wang X, Cheng B, Cheng Y, Luo H, Ti Y, Huang X, Liu Z, Zhang Yw, Zheng W‡, Zheng H‡. Protective role of L-3-n-butylphthalide in cognitive function and dysthymic disorders in mouse with chronic epilepsy. Frontiers in Pharmacology. 2018; 9:734.
26.Pan G, Chen Z, Zheng H, Zhang Yw, Xu H, Bu G, Zheng H, Li Y. Compensatory mechanisms modulate the neuronal excitability in a kainic acid-induced epilepsy mouse model. Frontiers in Neural Circuits. 2018; 12:48.
27.Sun L, Rong Z, Li W, Zheng H*, Xiao S*, Li X*. Identification of a Novel Hemizygous SQSTM1 Nonsense Mutation in Atypical Behavioral Variant Frontotemporal Dementia. Front Aging Neurosci. 2018 Feb 6;10:26. doi: 10.3389/fnagi.2018.00026. eCollection 2018.
28.Zheng H*, Jia L, Liu CC, Rong Z, Zhong L, Yang L, Chen XF, Fryer JD, Wang X, Zhang YW, Xu H, Bu G*. TREM2 Promotes Microglial Survival by Activating Wnt/β-Catenin Pathway. J Neurosci. 2017; 37(7): 1772-1784.
29.Li Y, Chen Z, Gao Y, Pan G, Zheng H, Zhang Y, Xu H, Bu G, Zheng H. Synaptic Adhesion Molecule Pcdh-γC5 Mediates Synaptic Dysfunction in Alzheimer's Disease. J Neurosci. 2017; 37(38): 9259-9268.
30.Zhan Y, Zheng H*, Wang C, Rong Z, Xiao N, Ma Q*, Zhang YW*. A novel presenilin 1 mutation (F388L) identified in a Chinese family with early-onset Alzheimer's disease. Neurobiol Aging. 2017; 50: 168.e1-168.e4.
31.Zhan L, Yao Y, Fu H, Li Z, Wang F, Zhang X, He W, Zheng W, Zhang Y, Zheng H*. Protective role of miR-23b-3p in kainic acid-induced seizure. Neuroreport. 2016; 27(10):764-8.
32.Wang F, Zheng H, Zhang X, Li Y, Gao Z, Wang Y, Liu X, Yao Y*. Successful surgery in lesional epilepsy secondary to posterior quandrant ulegyria coexisting with benign childhood focal epilepsy: A case report. Clin Neurol Neurosurg. 2016; 149:94-7.
33.Zheng H, Liu CC, Atagi Y, Chen XF, Jia L, Yang L, He W, Zhang X, Kang SS, Rosenberry TL, Fryer JD, Zhang YW, Xu H, Bu G*. Opposing roles of the triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells-like transcript 2 in microglia activation. Neurobiol Aging. 2016; 42:132-141.
34.Yang L, Liu CC, Zheng H, Kanekiyo T, Atagi Y, Jia L, Wang D, N'songo A, Can D, Xu H, Chen XF, Bu G. LRP1 modulates the microglial immune response via regulation of JNK and NF-κB signaling pathways. J Neuroinflammation. 2016; 13(1):304.
35.Zhong L, Chen XF, Wang T, Wang Z, Liao C, Wang Z, Huang R, Wang D, Li X, Wu L, Jia L, Zheng H, Painter M, Atagi Y, Liu CC, Zhang YW, Fryer JD, Xu H, Bu G. Soluble TREM2 induces inflammatory responses and enhances microglial survival. J Exp Med. 2017; 214(3):597-607.
36.Ye X, Zhang Y, Xu Q, Zheng H, Wu X, Qiu J, Zhang Z, Wang W, Shao Y, Xing HQ. HIV-1 Tat inhibits EAAT-2 through AEG-1 upregulation in models of HIV-associated neurocognitive disorder. 2017; 8(24):39922-39934.
37.Wang J, Zhang Y, Xu Q, Qiu J, Zheng H, Ye X, Xue Y, Yin Y, Zhang Z, Liu Y, Hao Y, Wei Q, Wang W, Mori K, Izumo S, Kubota R, Shao Y, Xing HQ. Menin mediates Tat-induced neuronal apoptosis in brain frontal cortex of SIV-infected macaques and in Tat-treated cells. Oncotarget. 2017; 8(11):18082-18094.
38.Fu Y, Zhao J, Atagi Y, Nielsen HM, Liu CC, Zheng H, Shinohara M, Kanekiyo T, Bu G*. Apolipoprotein E lipoprotein particles inhibit amyloid-β uptake through cell surface heparan sulphate proteoglycan. Mol Neurodegener. 2016; 11(1):37.
39.Atagi Y, Liu CC, Painter MM, Chen XF, Verbeeck C, Zheng H, Li X, Rademakers R, Kang SS, Xu H, Younkin S, Das P, Fryer JD, Bu G*. Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2). J Biol Chem. 2015; 290(43):26043-50.
40.Zheng H, Tang R, Yao Y, Ji Z, Cao Y, Liu Z, Peng F, Wang W, Can D, Xing H, Bu G, Xu H, Zhang YW*, Zheng W*. MiR-219 Protects Against Seizure in the Kainic Acid Model of Epilepsy. Mol Neurobiol. 53(1):1-7. 2016.
41.Zheng H, Wang X, Tang Z, Zheng W, Li Z*. The PI3K/Akt and ERK1/2 signaling pathways mediate the erythropoietin-modulated calcium influx in kainic acid-induced epilepsy. Neuroreport. 24(6):335-41.2013.
42.Zhu W, Zheng H, Shao X, Wang W, Yao Q, Li Z*. Excitotoxicity of TNFalpha derived from KA activated microglia on hippocampal neurons in vitro and in vivo. J Neurochem. 114(2):386-96. 2010.
43.Zheng H, Zhu W, Zhao H, Wang X, Wang W, Li Z*. Kainic acid-activated microglia mediate increased excitability of rat hippocampal neurons in vitro and in vivo: crucial role of interleukin-1beta. Neuroimmunomodulation. 17(1):31-38. 2010.
44.Wang X, Zheng H, Liu C, Zhu C, Wang W, Li Z*. Ciliary neurotrophic factor-treated astrocyte conditioned medium regulates the L-type calcium channel activity in rat cortical neurons. Neurochem Res. 33: 826-832. 2008.
45.Chen Y, Li D, Liu H, Xu H, Zheng H, Feng Q, Li W, Zhao C, Wang Z, Wang X*. Notch-1 signaling facilitates survivin expression in human non-small cell lung cancer cells. Cancer Biol Ther. 11(1): 14-21. 2011.
46.Gao SB, Feng ZJ, Xu B, Chen Y, Zheng HH, Yin P, Hua X*, Jin GH*. Menin represses malignant phenotypes of melanoma through regulating multiple pathways. J Cell Mol Med. 15（11）：2353-63. 2011.
