国家卫健委重点室科研骨干，人类分子遗传团队负责人；

国家重点研发计划科研骨干，黑龙江头雁计划科研骨干；

黑龙江省头雁计划引进人才，哈医大第四医院引进人才；

黑龙江省教育厅新质生产力智库专家，中国博士后科学基金评审专家库专家；

黑龙江省科协优秀青年科技人才库专家，黑龙江省科技厅人类遗传资源管理专家；

临床罕见病和常见疾病中，致病和风险变异的综合鉴定和评估，探索分子诊疗策略；

神经系统单基因和复杂疾病，及重度肥胖和胆汁淤积性肝病等代谢疾病的分子遗传，病生免疫机制，和管理策略。

1）主要依托于科技部国家重点研发计划（儿童神经发育异常的遗传调控研究）和黑龙江省头雁计划（疾病基因及分子靶点创新研究），近四年来独立和合作收集了神经发育异常病例约350例，重度肥胖约150例，胆汁淤积约60例，初步建立了临床队列，完成了常规的致病基因和变异筛查工作，共鉴定出约80个基因上的未知或已知致病变异，为后续病生免疫机制和临床干预策略的研究提供了分子基础。2）深度参与华中科大刘静宇教授和协和医大张学教授共同领衔的原发性家族性脑钙化（PFBC）致病基因鉴定项目，在国际上首次报道SLC20A2（PIT

2）的无机磷摄取功能缺陷是导致PFBC的主要原因，建立和全面描绘了Slc20a2（Pit2）纯合敲除小鼠中的脑钙化分布和行为学异常，为后续病生免疫机制和临床干预策略的研究奠定基础。深度参与北大医院杨勇教授和协和医大张学教授共同领衔的遗传性皮肤病致病基因的鉴定项目，该研究首次报道了HOXC13失去功能变异可导致纯发-甲型外胚叶发育不良。

3）长期聚焦于临床罕见病致病变异的鉴定工作，积极探索基因变异导致疾病的分子遗传和病生免疫机制，并致力开发管理策略。已在神经（神经发育和退行疾病，精神疾病），代谢（肥胖症、二型糖尿病、胆汁淤积疾病、炎症性肠炎），皮-眼-骨（外胚层发育不良、色素失禁症、先天性白内障、骨化性肌炎），血管（关节和动脉钙化），肿瘤（头颈肿瘤）等疾病的遗传研究中积累了广泛经验。

01, Li Y†, Wang X†, Zhang Z, Shi L*, Cheng L*, Zhang X*. Effect of the gut microbiome, plasma metabolome, peripheral cells, and inflammatory cytokines on obesity: a bidirectional two-sample Mendelian randomization study and mediation analysis. Front Immunol. 2024 Mar 15:15:1348347.

02, Zhang S†, Wang P†, Shi L†, Wang C, Zhu Z, Qi C, Xie Y, Yuan S, Cheng L*, Yin X*, Zhang X*. Exploring COVID-19 causal genes through disease-specific Cis-eQTLs. Virus Res. 2024 Apr:342:199341.

03, Wang P†, Zhang S†, Qi C, Wang C, Zhu Z, Shi L*, Cheng L*, Zhang X*. Blood microbial analyses reveal long-term effects of SARS-CoV-2 infection on patients who recovered from COVID-19. Comput Biol Med. 2024 Jan:168:107721.

04, Zhu Z†, Chen X†, Wang C, Zhang S, Yu R, Xie Y, Yuan S, Cheng L*, Shi L*, Zhang X*. An integrated strategy to identify COVID-19 causal genes and characteristics represented by LRRC37A2. J Med Virol. 2023 Feb;95(2):e28585.

05, Zhang Y†, Ren Y†, Zhang Y, Li Y, Xu C, Peng Z, Jia Y, Qiao S, Zhang Z, Shi L*. T-cell infiltration in the central nervous system and their association with brain calcification in Slc20a2-deficient mice. Front Mol Neurosci. 2023 Jan 20;16:1073723.

06, Qi C†, Cai Y†, Qian K†, Li X, Ren J, Wang P, Fu T, Zhao T, Cheng L*, Shi L*, Zhang X*. gutMDisorder v2.0: a comprehensive database for dysbiosis of gut microbiota in phenotypes and interventions. Nucleic Acids Res. 2023 Jan 6;51(D1):D717-D722.

07, Wang P†, Zhang S†, He G†, Du M, Qi C, Liu R, Zhang S, Cheng L*, Shi L*, Zhang X*. microbioTA: an atlas of the microbiome in multiple disease tissues of Homo sapiens and Mus musculus. Nucleic Acids Res. 2023 Jan 6;51(D1):D1345-D1352.

08, Zhang YH†, He YF, Yue H, Zhang YN, Shi L*, Jin B, Dong P. Solitary hyoid plasmacytoma with unicentric Castleman disease: A case report and review of literature. World J Clin Cases. 2022 Dec 26;10(36):13364-13372.

09, Shen Y†, Shu S†, Ren Y†, Xia W, Chen J, Dong L, Ge H, Fan S, Shi L*, Peng B*, Zhang X. Case Report: Two Novel Frameshift Mutations in SLC20A2 and One Novel Splice Donor Mutation in PDGFB Associated with Primary Familial Brain Calcification. Front Genet. 2021 May 7;12:643452.

10, Ren Y†, Shen Y, Si N, Fan S, Zhang Y, Xu W, Shi L*, Zhang X*. Slc20a2-Deficient Mice Exhibit Multisystem Abnormalities and Impaired Spatial Learning Memory and Sensorimotor Gating but Normal Motor Coordination Abilities. Front Genet. 2021 Apr 6;12:639935.

11, Yuan F†, Yuan R, Ren D, Bi Y, Niu W, Guo Z, Wu X, Xu F, Sun Q, Ma G, Yang F, Zhu Y, Yu T, Li X, He L, Shi L*, He G*. A novel NR3C2 polymorphism and the increased thyroid-stimulating hormone concentration are associated with venlafaxine treatment outcome in Chinese Han MDD patients. Psychiatry Res. 2020 Feb;284:112690.

12, Lin Z†, Chen Q†, Shi L, Lee M, Giehl KA, Tang Z, Wang H, Zhang J, Yin J, Wu L, Xiao R, Liu X, Dai L, Zhu X, Li R, Betz RC, Zhang X*, Yang Y*. Loss-of-function mutations in HOXC13 cause pure hair and nail ectodermal dysplasia. Am J Hum Genet. 2012 Nov 2;91(5):906-11.

13, Wang C†, Li Y†, Shi L†, Ren J, Patti M, Wang T, de Oliveira JR, Sobrido MJ, Quintáns B, Baquero M, Cui X, Zhang XY, Wang L, Xu H, Wang J, Yao J, Dai X, Liu J, Zhang L, Ma H, Gao Y, Ma X, Feng S, Liu M, Wang QK, Forster IC, Zhang X*, Liu JY*. Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet. 2012 Feb 12;44(3):254-6.

14, Liu Q†, Qi Z, Wan XH, Li JY, Shi L, Lu Q, Zhou XQ, Qiao L, Wu LW, Liu XQ, Yang W, Liu Y, Cui LY*, Zhang X*. Mutations in PRRT2 result in paroxysmal dyskinesias with marked variability in clinical expression. J Med Genet. 2012 Feb;49(2):79-82.