Yiqiang Cai, PhD, MD
Associate Research Scientist (Nephrology)
Research & Publications
Biography
News
Extensive Research Description
My current research is focused on the study of molecular basis of ADPKD pathogenesis. By establishing cell-based model and BAC-transgenic mouse model, we are trying to answer the following questions: 1) How are polycystin-1 and polycystin-2 trafficking to cilia regulated; 2) What is the consequence that trafficking defect of the polycystins cause in the cystogenesis/PKD pathogenesis; 3) What is the molecular basis underlying the mutations of PKD1 and PKD2 genes, 4) How is the polycystin-2 phosphorylation regulated, and 5) What is the role that regulation of polycystin-2 phosphorylation plays on the PKD pathogenesis.
Coauthors
Research Interests
Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Diseases
Selected Publications
- XBP1 Activation Reduces Severity of Polycystic Kidney Disease due to a Nontruncating Polycystin-1 Mutation in MiceKrappitz M, Bhardwaj R, Dong K, Staudner T, Yilmaz DE, Pioppini C, Westergerling P, Ruemmele D, Hollmann T, Nguyen TA, Cai Y, Gallagher AR, Somlo S, Fedeles S. XBP1 Activation Reduces Severity of Polycystic Kidney Disease due to a Nontruncating Polycystin-1 Mutation in Mice. Journal Of The American Society Of Nephrology 2022, 34: 110-121. PMID: 36270750, PMCID: PMC10101557, DOI: 10.1681/asn.2021091180.
- Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell DeathDecuypere JP, Van Giel D, Janssens P, Dong K, Somlo S, Cai Y, Mekahli D, Vennekens R. Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death. International Journal Of Molecular Sciences 2021, 22: 13511. PMID: 34948309, PMCID: PMC8706473, DOI: 10.3390/ijms222413511.
- Polycystin 2 regulates mitochondrial Ca2+ signaling, bioenergetics, and dynamics through mitofusin 2Kuo IY, Brill AL, Lemos FO, Jiang JY, Falcone JL, Kimmerling EP, Cai Y, Dong K, Kaplan DL, Wallace DP, Hofer AM, Ehrlich BE. Polycystin 2 regulates mitochondrial Ca2+ signaling, bioenergetics, and dynamics through mitofusin 2. Science Signaling 2019, 12 PMID: 31064883, PMCID: PMC6855602, DOI: 10.1126/scisignal.aat7397.
- Polycystic Kidney DiseaseCai Y. Polycystic Kidney Disease. 2016, 3653-3658. DOI: 10.1007/978-3-662-46875-3_4667.
- Altered trafficking and stability of polycystins underlie polycystic kidney diseaseCai Y, Fedeles SV, Dong K, Anyatonwu G, Onoe T, Mitobe M, Gao JD, Okuhara D, Tian X, Gallagher AR, Tang Z, Xie X, Lalioti MD, Lee AH, Ehrlich BE, Somlo S. Altered trafficking and stability of polycystins underlie polycystic kidney disease. Journal Of Clinical Investigation 2014, 124: 5129-5144. PMID: 25365220, PMCID: PMC4348948, DOI: 10.1172/jci67273.
- A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formationFedeles SV, Tian X, Gallagher AR, Mitobe M, Nishio S, Lee SH, Cai Y, Geng L, Crews CM, Somlo S. A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation. Nature Genetics 2011, 43: 639-647. PMID: 21685914, PMCID: PMC3547075, DOI: 10.1038/ng.860.
- Polycystic Kidney DiseaseCai Y. Polycystic Kidney Disease. 2011, 2947-2950. DOI: 10.1007/978-3-642-16483-5_4667.
- Polycystin-2 Activation by Inositol 1,4,5-Trisphosphate-induced Ca2+ Release Requires Its Direct Association with the Inositol 1,4,5-Trisphosphate Receptor in a Signaling Microdomain*Sammels E, Devogelaere B, Mekahli D, Bultynck G, Missiaen L, Parys JB, Cai Y, Somlo S, De Smedt H. Polycystin-2 Activation by Inositol 1,4,5-Trisphosphate-induced Ca2+ Release Requires Its Direct Association with the Inositol 1,4,5-Trisphosphate Receptor in a Signaling Microdomain*. Journal Of Biological Chemistry 2010, 285: 18794-18805. PMID: 20375013, PMCID: PMC2881802, DOI: 10.1074/jbc.m109.090662.
- Regulation of ciliary trafficking of polycystin-2 and the pathogenesis of autosomal dominant polycystic kidney disease.Cai Y, Tang Z. Regulation of ciliary trafficking of polycystin-2 and the pathogenesis of autosomal dominant polycystic kidney disease. Journal Of Central South University. Medical Sciences. 2010, 35: 93-9. PMID: 20197605, DOI: 10.3969/j.issn.1672-7347.2010.02.001.
- Polycystin-1 C-terminal Cleavage Is Modulated by Polycystin-2 Expression*Bertuccio CA, Chapin HC, Cai Y, Mistry K, Chauvet V, Somlo S, Caplan MJ. Polycystin-1 C-terminal Cleavage Is Modulated by Polycystin-2 Expression*. Journal Of Biological Chemistry 2009, 284: 21011-21026. PMID: 19491093, PMCID: PMC2742866, DOI: 10.1074/jbc.m109.017756.
- Arachidonic acid cytochrome P450 4F2 in hypertension: what can we learn from a transgenic mouse model??Cai Y. Arachidonic acid cytochrome P450 4F2 in hypertension: what can we learn from a transgenic mouse model?? Kidney International 2009, 75: 1253-1254. PMID: 19483747, DOI: 10.1038/ki.2009.82.
- Regulation of Polycystin‐1 C terminal cleavage by Polycystin‐2Bertuccio C, Cai Y, Somlo S, Caplan M. Regulation of Polycystin‐1 C terminal cleavage by Polycystin‐2. The FASEB Journal 2008, 22: 942.9-942.9. DOI: 10.1096/fasebj.22.1_supplement.942.9.
- Too Much of a Good Thing: Does Nek8 Link Polycystic Kidney Disease and Nephronophthisis?Cai Y, Somlo S. Too Much of a Good Thing: Does Nek8 Link Polycystic Kidney Disease and Nephronophthisis? Journal Of The American Society Of Nephrology 2008, 19: 418-420. PMID: 18272836, DOI: 10.1681/asn.2008010084.
- Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motifGeng L, Okuhara D, Yu Z, Tian X, Cai Y, Shibazaki S, Somlo S. Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif. Journal Of Cell Science 2006, 119: 1383-1395. PMID: 16537653, DOI: 10.1242/jcs.02818.
- Polycystin-2 Regulates Proliferation and Branching Morphogenesis in Kidney Epithelial Cells*Grimm DH, Karihaloo A, Cai Y, Somlo S, Cantley LG, Caplan MJ. Polycystin-2 Regulates Proliferation and Branching Morphogenesis in Kidney Epithelial Cells*. Journal Of Biological Chemistry 2005, 281: 137-144. PMID: 16278216, DOI: 10.1074/jbc.m507845200.
- Polyductin, the PKHD1 gene product, comprises isoforms expressed in plasma membrane, primary cilium, and cytoplasmMenezes LF, Cai Y, Nagasawa Y, Silva AM, Watkins ML, Da Silva AM, Somlo S, Guay-Woodford LM, Germino GG, Onuchic LF. Polyductin, the PKHD1 gene product, comprises isoforms expressed in plasma membrane, primary cilium, and cytoplasm. Kidney International 2004, 66: 1345-1355. PMID: 15458427, DOI: 10.1111/j.1523-1755.2004.00844.x.
- Mutations in SEC63 cause autosomal dominant polycystic liver diseaseDavila S, Furu L, Gharavi AG, Tian X, Onoe T, Qian Q, Li A, Cai Y, Kamath PS, King BF, Azurmendi PJ, Tahvanainen P, Kääriäinen H, Höckerstedt K, Devuyst O, Pirson Y, Martin RS, Lifton RP, Tahvanainen E, Torres VE, Somlo S. Mutations in SEC63 cause autosomal dominant polycystic liver disease. Nature Genetics 2004, 36: 575-577. PMID: 15133510, DOI: 10.1038/ng1357.
- The N-terminal Extracellular Domain Is Required for Polycystin-1-dependent Channel Activity*Babich V, Zeng WZ, Yeh BI, Ibraghimov-Beskrovnaya O, Cai Y, Somlo S, Huang CL. The N-terminal Extracellular Domain Is Required for Polycystin-1-dependent Channel Activity*. Journal Of Biological Chemistry 2004, 279: 25582-25589. PMID: 15060061, DOI: 10.1074/jbc.m402829200.
- Deficiency of polycystin‐2 reduces Ca2+ channel activity and cell proliferation in ADPKD lymphoblastoid cellsAguiari G, Banzi M, Gessi S, Cai Y, Zeggio E, Manzati E, Piva R, Lambertini E, Ferrari L, Peters DJ, Lanza F, Harris PC, Borea PA, Somlo S, del Senno L. Deficiency of polycystin‐2 reduces Ca2+ channel activity and cell proliferation in ADPKD lymphoblastoid cells. The FASEB Journal 2004, 18: 884-886. PMID: 15001556, DOI: 10.1096/fj.03-0687fje.
- Calcium Dependence of Polycystin-2 Channel Activity Is Modulated by Phosphorylation at Ser812 *Cai Y, Anyatonwu G, Okuhara D, Lee KB, Yu Z, Onoe T, Mei CL, Qian Q, Geng L, Wiztgall R, Ehrlich BE, Somlo S. Calcium Dependence of Polycystin-2 Channel Activity Is Modulated by Phosphorylation at Ser812 *. Journal Of Biological Chemistry 2004, 279: 19987-19995. PMID: 14742446, DOI: 10.1074/jbc.m312031200.
- Analysis of the Polycystins in Aortic Vascular Smooth Muscle CellsQian Q, Li M, Cai Y, Ward CJ, Somlo S, Harris PC, Torres VE. Analysis of the Polycystins in Aortic Vascular Smooth Muscle Cells. Journal Of The American Society Of Nephrology 2003, 14: 2280-2287. PMID: 12937304, DOI: 10.1097/01.asn.0000080185.38113.a3.
- Polycystin-1 Distribution Is Modulated by Polycystin-2 Expression in Mammalian Cells*Grimm DH, Cai Y, Chauvet V, Rajendran V, Zeltner R, Geng L, Avner ED, Sweeney W, Somlo S, Caplan MJ. Polycystin-1 Distribution Is Modulated by Polycystin-2 Expression in Mammalian Cells*. Journal Of Biological Chemistry 2003, 278: 36786-36793. PMID: 12840011, DOI: 10.1074/jbc.m306536200.
- Altered expression pattern of polycystin-2 in acute and chronic renal tubular diseases.Obermüller N, Cai Y, Kränzlin B, Thomson RB, Gretz N, Kriz W, Somlo S, Witzgall R. Altered expression pattern of polycystin-2 in acute and chronic renal tubular diseases. Journal Of The American Society Of Nephrology 2002, 13: 1855-64. PMID: 12089381, DOI: 10.1097/01.asn.0000018402.33620.c7.
- Expression of PKD1 and PKD2 Transcripts and Proteins in Human Embryo and during Normal Kidney DevelopmentChauvet V, Qian F, Boute N, Cai Y, Phakdeekitacharoen B, Onuchic LF, Attié-Bitach T, Guicharnaud L, Devuyst O, Germino GG, Gubler MC. Expression of PKD1 and PKD2 Transcripts and Proteins in Human Embryo and during Normal Kidney Development. American Journal Of Pathology 2002, 160: 973-983. PMID: 11891195, PMCID: PMC1867156, DOI: 10.1016/s0002-9440(10)64919-x.
- Polycystin-2 is an intracellular calcium release channelKoulen P, Cai Y, Geng L, Maeda Y, Nishimura S, Witzgall R, Ehrlich BE, Somlo S. Polycystin-2 is an intracellular calcium release channel. Nature Cell Biology 2002, 4: 191-197. PMID: 11854751, DOI: 10.1038/ncb754.
- Cloning and Characterization of the Murine Pkd2 PromoterPark J, Li L, Cai Y, Hayashi T, Dong F, Maeda Y, Rubin C, Somlo S, Wu G. Cloning and Characterization of the Murine Pkd2 Promoter. Genomics 2000, 66: 305-312. PMID: 10873385, DOI: 10.1006/geno.2000.6197.
- Cardiac defects and renal failure in mice with targeted mutations in Pkd2Wu G, Markowitz G, Li L, D'Agati V, Factor S, Geng L, Tibara S, Tuchman J, Cai Y, Hoon Park J, van Adelsberg J, Hou H, Kucherlapati R, Edelmann W, Somlo S. Cardiac defects and renal failure in mice with targeted mutations in Pkd2. Nature Genetics 2000, 24: 75-78. PMID: 10615132, DOI: 10.1038/71724.
- The rat Pkd2 protein assumes distinct subcellular distributions in different organsObermüller N, Gallagher A, Cai Y, Gassler N, Gretz N, Somlo S, Witzgall R. The rat Pkd2 protein assumes distinct subcellular distributions in different organs. American Journal Of Physiology 1999, 277: f914-f925. PMID: 10600939, DOI: 10.1152/ajprenal.1999.277.6.f914.
- Aberrant splicing in the PKD2 gene as a cause of polycystic kidney disease.Reynolds DM, Hayashi T, Cai Y, Veldhuisen B, Watnick TJ, Lens XM, Mochizuki T, Qian F, Maeda Y, Li L, Fossdal R, Coto E, Wu G, Breuning MH, Germino GG, Peters DJ, Somlo S. Aberrant splicing in the PKD2 gene as a cause of polycystic kidney disease. Journal Of The American Society Of Nephrology 1999, 10: 2342-51. PMID: 10541293, DOI: 10.1681/asn.v10112342.
- Identification and Characterization of Polycystin-2, thePKD2 Gene Product*Cai Y, Maeda Y, Cedzich A, Torres V, Wu G, Hayashi T, Mochizuki T, Park J, Witzgall R, Somlo S. Identification and Characterization of Polycystin-2, thePKD2 Gene Product*. Journal Of Biological Chemistry 1999, 274: 28557-28565. PMID: 10497221, DOI: 10.1074/jbc.274.40.28557.
- Polycystin-2 expression is developmentally regulatedMarkowitz G, Cai Y, Li L, Wu G, Ward L, Somlo S, D’Agati V. Polycystin-2 expression is developmentally regulated. American Journal Of Physiology 1999, 277: f17-f25. PMID: 10409293, DOI: 10.1152/ajprenal.1999.277.1.f17.
- Mutations in autosomal dominant polycystic kidney disease 2 gene: Reduced expression of PKD2 protein in lymphoblastoid cellsAguiari G, Manzati E, Penolazzi L, Micheletti F, Augello G, De Vitali E, Cappelli G, Cai Y, Reynolds D, Somlo S, Piva R, del Senno L. Mutations in autosomal dominant polycystic kidney disease 2 gene: Reduced expression of PKD2 protein in lymphoblastoid cells. American Journal Of Kidney Diseases 1999, 33: 880-885. PMID: 10213643, DOI: 10.1016/s0272-6386(99)70420-8.
- Identification ofPKD2L,a HumanPKD2-Related Gene: Tissue-Specific Expression and Mapping to Chromosome 10q25Wu G, Hayashi T, Park J, Dixit M, Reynolds D, Li L, Maeda Y, Cai Y, Coca-Prados M, Somlo S. Identification ofPKD2L,a HumanPKD2-Related Gene: Tissue-Specific Expression and Mapping to Chromosome 10q25. Genomics 1998, 54: 564-568. PMID: 9878261, DOI: 10.1006/geno.1998.5618.
- Somatic Inactivation of Pkd2 Results in Polycystic Kidney DiseaseWu G, D'Agati V, Cai Y, Markowitz G, Park J, Reynolds D, Maeda Y, Le T, Hou H, Kucherlapati R, Edelmann W, Somlo S. Somatic Inactivation of Pkd2 Results in Polycystic Kidney Disease. Cell 1998, 93: 177-188. PMID: 9568711, DOI: 10.1016/s0092-8674(00)81570-6.
- Molecular Cloning, cDNA Sequence Analysis, and Chromosomal Localization of MousePkd2Wu G, Mochizuki T, Le T, Cai Y, Hayashi T, Reynolds D, Somlo S. Molecular Cloning, cDNA Sequence Analysis, and Chromosomal Localization of MousePkd2. Genomics 1997, 45: 220-223. PMID: 9339380, DOI: 10.1006/geno.1997.4920.
- Characterization of the Exon Structure of the Polycystic Kidney Disease 2 Gene (PKD2)Hayashi T, Mochizuki T, Reynolds D, Wu G, Cai Y, Somlo S. Characterization of the Exon Structure of the Polycystic Kidney Disease 2 Gene (PKD2). Genomics 1997, 44: 131-136. PMID: 9286709, DOI: 10.1006/geno.1997.4851.
- PKD1 interacts with PKD2 through a probable coiled-coil domainQian F, Germino F, Cai Y, Zhang X, Somlo S, Germino G. PKD1 interacts with PKD2 through a probable coiled-coil domain. Nature Genetics 1997, 16: 179-183. PMID: 9171830, DOI: 10.1038/ng0697-179.
- PKD2, a Gene for Polycystic Kidney Disease That Encodes an Integral Membrane ProteinMochizuki T, Wu G, Hayashi T, Xenophontos S, Veldhuisen B, Saris J, Reynolds D, Cai Y, Gabow P, Pierides A, Kimberling W, Breuning M, Deltas C, Peters D, Somlo S. PKD2, a Gene for Polycystic Kidney Disease That Encodes an Integral Membrane Protein. Science 1996, 272: 1339-1342. PMID: 8650545, DOI: 10.1126/science.272.5266.1339.