邵乐平

邵乐平

博士

教授

博士生导师

院所：

医药学院

办公电话：

18661808738

电子邮箱：

lepingshao@163.com

联系地址：

山东省青岛市东海中路5号青岛市市立医院肾病科

研究方向：

1. 遗传性肾病；

2. 剪切调控机制与原发性肾小管疾病；

3.海洋药物在肾脏疾病中的应用及机制研究；

个人简介

从事原发性肾小管疾病以及电解质和酸碱平衡紊乱的诊治研究。国内首次诊断并报道常染色显性遗传性远端肾小管酸中毒（RTA）、常染色体隐性遗传性远端RTA、3型原发性高草酸尿症、假性醛固酮减少症2E型、成人果糖1,6-二磷酸酶缺陷以及家族性低血镁高尿钙肾钙质沉积症等多种疾病，病人来自全国20多个省、直辖市或自治区。国内最早成立了肾脏罕见病网站（www.shenzanghanjianbing.com）。以首位获山东省科技进步奖二等奖；发表论文70余篇，以首位或通讯作者发表SCI收录论文35篇，SCI收录论文影响因子累计130余分，他引200余次；主持国家自然科学基金面上项目3项和省优秀中青年科学家科研奖励基金1项。

教育背景

2004年8月至2007年6月

上海交通大学医学院

内科学

博士

2001年9月至2004年6月

青岛大学医学院

眼科学

硕士

工作经历

2018年8月至今

青岛市市立医院

主任医师

2007年8月至2018年8月

青岛大学医学院附属医院

副主任医师

学术兼职

青岛市肾病质控中心主任，山东省医学会肾病分会委员，山东省医师协会肾病分会副主任委员，华东六省一市肾脏协作委员会委员，山东省研究型医院协会肾病分会副主任委员，中国康复医学会肾病分会委员。

荣誉奖励

1.      2019年青岛市优秀学科带头人

2.      2015年山东省有突出贡献的中青年专家，

3.      2014年山东省十佳青年医师，

4.      2013年青岛市青年科技奖获得者

研究进展

反义寡核苷酸治疗单基因病正引起越来越多关注。巴特综合征(BS)是肾单位髓袢升支粗段NaCl重吸收障碍造成的罕见的失盐性肾小管疾病。1型BS(BS1)由基因SLC12A1(MIM600839)突变导致。本团队前期发现患者携带SLC12A1基因11号外显子(E11)深部单个核苷酸替代变异(c.1435C>G)，推测为错义变异，但体外功能研究证实该错义变异存在正常的活性，与表型不符。进一步的研究证实该变异实际为剪切突变，导致E11的剪切跳过(ΔE11)。c.1435C>G可能导致了外显子剪接增强子破坏并伴随沉默子产生，E11存在较弱的5’剪接位点(5’ss)，且下游内含子存在强力的剪接抑制基序，该特点决定了ΔE11的易感性。本研究拟从体外剪接实验和人源化基因敲入小鼠模型研究E11的剪接调控网络，探讨c.1435C>G的发病机制，设计并研究靶向反义寡核苷酸在细胞和动物模型中的治疗作用。

代表性成果

代表性论文(第一或通讯作者)：

1.      Guo W, Song Q, Zhang R, Xin Q, Liu Z, Lang Y, Zhao X, Shao L. Mutation analysis and Investigation of Phenotype in 51 patients with primary distal renal tubular acidosis. Clin Genet. 2021 Jun 23. doi: 10.1111/cge.14011. (SCI, IF=4.438)

2.      Zhang R, Chen Z, Song Q, Wang S, Liu Z, Zhao X, Shi X, Guo W, Lang Y, Bottillo I, Shao L. Identification of seven exonic variants in the SLC4A1, ATP6V1B1, and ATP6V0A4 genes that alter RNA splicing by minigene assay. Hum Mutat. 2021 Jun 22. doi: 10.1002/humu.24246. (SCI, IF=4.878)

3.      Miao Z, Gao Y, Bindels RJ, Yu W, Lang Y, Chen N, Ren H, Sun F, Li Y, Wang X, Shao L. Coexistence of normotensive primary aldosteronism in two patients with Gitelman's syndrome and novel thiazide-sensitive Na-Cl cotransporter mutations. Eur J Endocrinol. 2009 Aug;161(2):275-83.（SCI, IF=6.664）

4.      Yue Han, Hai Cheng, Shihong Shao, Yanhua Lang, Xiangzhong Zhao, Yi Lin, Sai Wang, Xiaomeng Shi, Zhiying Liu, LepingShao . Thirteen novel CLCNKB variants and genotype/phenotype association study in 42 Chinese patients with Bartter syndrome type 3.  Endocrine.  2020 Apr;68(1):192-202.  (SCI, IF=3.633)

5.      Luan H, Wang C, Xing X, Shao L. Cast nephropathy associated with monoclonal immunoglobulin M-secreting mucosa-associated lymphoid tissue B-cell lymphoma. Clin Nephrol.  2019 Jun;91(6):380-385. （SCI, IF=1.7）

6.      Han Y, Zhao X, Wang S, Wang C, Tian D, Lang Y, Bottillo I, Wang X, Shao L. Eleven novel SLC12A1 variants and an exonic mutation cause exon skipping in Bartter syndrome type I. Endocrine. 2019 Jun;64(3):708-718. （SCI, IF=3.633）

7.      Wang S, Zhao X, Zhang R, Wang C, Han Y, Shao L. Identification of ten novel SLC5A2 mutations and determination of the renal threshold for glucose excretion in Chinese patients with familial renal glucosuria. Clin Chim Acta. 2019 Mar;490:102-106. （SCI, IF=3.786）

8.      Zhao X, Lu J, Gao Y, Wang X, Lang Y, Shao L . Novel compound heterozygous ATP6V1B1 mutations in a Chinese child patient with primary distal renal tubular acidosis: a case report. BMC Nephrol. 2018 Dec 17;19(1):364. （SCI, IF=2.388）

9.      Zhang R, Wang C, Lang Y, Gao Y, Chen Z, Lu J, Zhao X, Shao L. Five Novel Mutations in Chinese Children with Primary Distal Renal Tubular Acidosis. Genet Test Mol Biomarkers. 2018 Oct;22(10):599-606. （SCI, IF=1.795）

10.  Zhang R, Wang J, Wang Q, Han Y, Liu X, Bottillo I, Lang Y, Shao L. Identification of a novel TSC2 c.3610G>A, p.G1204R mutation contribute to aberrant splicing in a patient with classical tuberous sclerosis complex: a case report. BMC Med Genet. 2018 Sep 20;19(1):173. （SCI, IF=2.103）

11.  Shao L, Cui L, Lu J, Lang Y, Bottillo I, Zhao X. A novel mutation in exon 9 of Cullin 3 gene contributes to aberrant splicing in pseudohypoaldosteronism type II. FEBS Open Bio. 2018 Feb 10;8(3):461-469. （SCI, IF=2.693）

12.  Jing-Ru Lu, Cui Wang, Le-Ping Shao. A Chinese Adult Patient with Fructose 1,6-bisphosphatase Deficiency. CHINESE MED J. 2017, 130, 2009-2010. （SCI, IF=2.628）

13.  Zhao X, Cui L, Lang Y, Liu T, Lu J, Wang C, Tuffery-Giraud S, Bottillo I, Wang X, Shao L. A recurrent deletion in the SLC5A2 gene including the intron 7 branch site responsible for familial renal glucosuria. Sci Rep. 2016 Sep 26;6:33920. （SCI, IF=5.228）

14.  Wang C, Lu J, Lang Y, Liu T, Wang X, Zhao X, Shao L. Two novel AGXT mutations identified in primary hyperoxaluria type-1 and distinct morphological and structural difference in kidney stones. Sci Rep. 2016 Sep 20;6:33652. （SCI, IF=5.228）

15.  Liu T, Wang C, Lu J, Zhao X, Lang Y, Shao L. Genotype/Phenotype Analysis in 67 Chinese Patients with Gitelman's Syndrome. Am J Nephrol. 2016;44(2):159-68. （SCI, IF=3.754）

16.  Wang X, Zhao X, Wang X, Yao J, Zhang F, Lang Y, Tuffery-Giraud S, Bottillo I, Shao L. Two Novel HOGA1 Splicing Mutations Identified in a Chinese Patient with Primary Hyperoxaluria Type 3. Am J Nephrol. 2015;42(1):78-84. （SCI, IF=3.754）

17.  Gao Y, Xu Y, Li Q, Lang Y, Dong Q, Shao L. Mutation analysis and audiologic assessment in six Chinese children with primary distal renal tubular acidosis. Ren Fail. 2014 Sep;36(8):1226-32. （SCI, IF=2.606）

18.  Shao L, Gao Y, Xu Y, Lang Y. Percutaneous Transluminal Revascularization following an Angiotensin Receptor Blocker: Successful Treatment for Flash Pulmonary Edema and Hyponatremic Hypertensive Syndrome. Cardiorenal Med. 2012 Aug;2(3):184-189. （SCI, IF=2.041）

19.  Shao L, Lang Y, Wang Y, Gao Y, Zhang W, Niu H, Liu S, Chen N. High-frequency variant p.T60M in NaCl cotransporter and blood pressure variability in Han Chinese. Am J Nephrol. 2012;35(6):515-9.（SCI, IF=3.754）

20.  Shao L, Xu Y, Dong Q, Lang Y, Yue S, Miao Z.A novel SLC4A1 variant in an autosomal dominant distal renal tubular acidosis family with a severe phenotype. Endocrine. 2010 Jun;37(3):473-8. （SCI, IF=3.633）

21.  Qin L, Shao L, Ren H, Wang W, Pan X, Zhang W, Wang Z, Shen P, Chen N. Identification of five novel variants in the thiazide-sensitive NaCl co-transporter gene in Chinese patients with Gitelman syndrome. Nephrology (Carlton). 2009 Feb;14(1):52-8. （SCI, IF=2.506）

22.  Shao L, Liu L, Miao Z, Ren H, Wang W, Lang Y, Yue S, Chen N. A novel SLC12A3 splicing mutation skipping of two exons and preliminary screening for alternative splice variants in human kidney. Am J Nephrol. 2008;28(6):900-7.（SCI, IF=3.754）

23.  Shao L, Ren H, Wang W, Zhang W, Feng X, Li X, Chen N. Novel SLC12A3 mutations in Chinese patients with Gitelman's syndrome. Nephron Physiol. 2008;108(3):p29-36.（SCI, IF=3.455）

24.  Yue Han, Yi Lin, Qing Sun, Shujuan Wang, Yanxia Gao, Leping Shao. Mutation spectrum of Chinese patients with Bartter Syndrome. Oncotarget. 2017 Sep 27;8(60):101614-101622. （SCI, IF=5.2）

25.  Wei Zhang, Feng Xue,Leping Shao. Clinical Features and Prognostic Factors of Ten Patients with Renal Failure Caused by IgG4-related Retroperitoneal Fibrosis. Oncotarget. 2017 Dec 7;9(2):2858-2865. （SCI, IF=5.2）

26.  Lu J, Zhao X, Paiardini A, Lang Y, Bottillo I, Shao L. Familial hypomagnesaemia, Hypercalciuria and Nephrocalcinosis associated with a novel mutation of the highly conserved leucine residue 116 of Claudin 16 in a Chinese patient with a delayed diagnosis: a case report. BMC Nephrol. 2018 Jul 13;19(1):181. （SCI, IF=2.388）

27.  Zhang R, Chen Z, Lang Y, Shao S, Cai Y, You Q, Sun Y, Wang S, Shi X, Liu Z, Guo W, Han Y, Shao L. Sudden onset of nephrotic syndrome in an asymptomatic Fabry patient: a case report. Ren Fail. 2020 Nov;42(1):958-965. （SCI, IF=2.606）

28.  Zuo J, Guo W, Wang S, Lang Y, Wang S, Shi X, Zhang R, Zhao X, Han Y, Shao L. Eight novel KCNJ1 variants and parathyroid hormone overaction or resistance in 5 probands with Bartter syndrome type 2. Clin Chim Acta. 2020 Dec;511:248-254. (SCI, IF=3.786)

29.  Shao L, Jiang W, Wang W, Cai Y, Sun Y, Zhang R, Bian L, Fu H, Zhang S, Mou C, Du H, You Q, Hua J, Fan X, Gao Y, Guo W. Concurrent non-crystalline light chain proximal tubulopathy and light chain deposition disease: a case report. Nephrology (Carlton). 2021 May;26(5):485-486. (SCI, IF=2.506)

30.  Wang S, Wang Y, Wang J, Liu Z, Zhang R, Shi X, Han Y, Guo W, Bottillo I, Shao L. Six Exonic Variants in the SLC5A2 Gene Cause Exon Skipping in a Minigene Assay. Front Genet. 2020 Nov 5;11:585064. (SCI, IF=4.599)

31.  Wang S, Dong B, Wang C, Lu J, Shao L. From Bartter's syndrome to renal tubular acidosis in a patient with Hashimoto's thyroiditis: A case report. Clin Nephrol. 2020 Sep;94(3):150-154. (SCI, IF=0.975)

32.  Shao L.  A novel compound heterozygous variant of the SLC12A3 gene in Gitelman syndrome with diabetes and the choices of the appropriate hypoglycemic drugs.  BMC Medical Genomics. 2021 Aug 4;14(1):198.. (SCI, IF=2.57) .

33.  Liu Z, Zhang H, Zhao S, Zhang Q, Zhang R, Han Y, Shao L, Zhao X. Novel gain-of-function mutation of TRPC6 Q134P contributes to late onset focal segmental glomerulosclerosis in a Chinese pedigree. Nephrology (Carlton). 2021 Aug 13. doi: 10.1111/nep.13963. （SCI, IF=2.5）

项目课题（承担在研）

1. 国家自然科学基金面上项目（82170717），1型Bartter综合征致病基因SLC12A1变异c.1435C>G发病机制暨个体化反义寡核苷酸治疗初步研究，55万，起止：202201-202512

2. 国家自然科学基金面上项目（81873594），家族性高血钾高血压致病基因CUL3突变c.1221A>G的发病机制和剪接调控寡核苷酸的治疗干预研究，60万，起止：201901-202212