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Stefan Somlo, MD

C. N. H. Long Professor of Medicine (Nephrology) and Professor of Genetics; Chief, Section of Nephrology

Research & Publications
Biography
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Research Summary

The goal of our laboratory is to understand the human polycystic diseases of the kidney and liver so that specific treatments can be developed. As a group, these diseases result in the progressive disruption of the normal structure and function of the affected organs leading to the symptoms that patients experience. To achieve our goal, we begin by discovering the genes responsible for these diseases in patient families and then proceed to studying the functions of the protein products of these genes in cells and tissues. We have discovered nine genes for the polycystic diseases so far and we are working to understand how they normally work together to prevent disease from occurring. As we understand more and more about the normal functions of these human disease genes, we expect to successfully translate this understanding into specific treatments for patients and families affected by polycystic kidney and liver diseases.

Specialized Terms: Genetic kidney and liver disease; Cilia function; Polycystin function

Extensive Research Description

The primary focus of our laboratory is understand the pathogenesis of polycystic kidney and liver diseases (ADPKD, PCLD, ARPKD). These diseases are the most prominent among a larger group of pleiotropic human genetic diseases which share fibrocystic deterioration of the kidney and liver as a key phenotypic feature and whose pathogenesis is related to the functioning of the primary cilium and basal body complex. Study of these diseases have uncovered the central role of cilia in novel signaling pathways and in establishing and maintaining three dimensional tissue structure. Therefore, understanding the mechanism of polycystic diseases will not only shed light on diseases for which there are no therapies currently but will also uncover general principles of the functioning of cilia in human biology.

We have taken a longitudinal approach to understanding the pathogenesis of polycystic kidney disease beginning with discovery of human disease genes for ADPKD (PKD2), ARPKD (PKHD1) and six genes for isolated dominant polycystic liver disease. While we continue our gene discovery efforts using next generation sequencing approaches (whole exome sequencing), our lab now seeks to define the cellular pathways in which the ADPKD-gene products (PKD1, PKD2) function and to translate these findings to treatments for ADPKD. A central principle of our current approach is need to address disease molecular processes impacting polycystic kidney and liver diseases using novel genetically engineered mouse models. To this end, we have developed a series of conditional and inducible mouse models of the relevant human disease genes and combined them with bacterial artificial chromosome (BAC) transgenic lines modified by recombineering to define the mechanisms of ADPKD, PCLD and ARPKD in vivo. Specific projects include dissection of the molecular pathways of trafficking of PKD1 and PKD2, to cilia, the inter-relationship of cilia function with PKD1 and PKD2 signaling, and the interaction of polycystic diseases with the unfolded protein response. We continue to keep in focus the need to develop principles to guide therapy in ADPKD based on basic science discoveries.

Coauthors

Research Interests

Cilia; Genetics; Kidney Diseases; Liver Diseases; Nephrology; TRPP Cation Channels

Selected Publications

Corrigendum to “WCN23-1242 Genetic interaction between XBP1 and Pkd1 modulates ADPKD progression” [Kidney International Reports Volume 8, Issue 3, Supplement, March 2023, Page S250]Krappitz M, Pioppini C, Bhardwaj R, Duygu E, Hollmann T, Somlo S, Fedeles S. Corrigendum to “WCN23-1242 Genetic interaction between XBP1 and Pkd1 modulates ADPKD progression” [Kidney International Reports Volume 8, Issue 3, Supplement, March 2023, Page S250]. Kidney International Reports 2023, 8: 2182. PMID: 37850015, PMCID: PMC10577355, DOI: 10.1016/j.ekir.2023.08.001.
Metabolic effects of polycystin-1 C-terminal tail (CTT) expression in Pkd1-KO miceOnuchic L, Padovano V, Schena G, Shi X, Dong K, Rajendran V, Rai V, Pandya R, Gresko N, Shen H, Somlo S, Caplan M. Metabolic effects of polycystin-1 C-terminal tail (CTT) expression in Pkd1-KO mice. Physiology 2023, 38: 5731616. DOI: 10.1152/physiol.2023.38.s1.5731616.
The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashionOnuchic L, Padovano V, Schena G, Rajendran V, Dong K, Shi X, Pandya R, Rai V, Gresko N, Ahmed O, Lam T, Wang W, Shen H, Somlo S, Caplan M. The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion. Nature Communications 2023, 14: 1790. PMID: 36997516, PMCID: PMC10063565, DOI: 10.1038/s41467-023-37449-1.
Hypomorphic PKD1 Alleles Impact Disease Variability in Autosomal Dominant Polycystic Kidney DiseaseGulati A, Dahl N, Hartung E, Clark S, Moudgil A, Goodwin J, Somlo S. Hypomorphic PKD1 Alleles Impact Disease Variability in Autosomal Dominant Polycystic Kidney Disease. Kidney360 2023, 4: 387-392. PMID: 36706243, PMCID: PMC10103195, DOI: 10.34067/kid.0000000000000064.
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.
An update on ductal plate malformations and fibropolycystic diseases of the liverMirza H, Besse W, Somlo S, Weinreb J, Kenney B, Jain D. An update on ductal plate malformations and fibropolycystic diseases of the liver. Human Pathology 2022, 132: 102-113. PMID: 35777701, DOI: 10.1016/j.humpath.2022.06.022.
Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies ConferenceParticipants K, Köttgen A, Gall E, Halbritter J, Kiryluk K, Mallett A, Parekh R, Rasouly H, Sampson M, Tin A, Antignac C, Ars E, Bergmann C, Bleyer A, Bockenhauer D, Devuyst O, Florez J, Fowler K, Franceschini N, Fukagawa M, Gale D, Gbadegesin R, Goldstein D, Grams M, Greka A, Gross O, Guay-Woodford L, Harris P, Hoefele J, Hung A, Knoers N, Kopp J, Kretzler M, Lanktree M, Lipska-Ziętkiewicz B, Nicholls K, Nozu K, Ojo A, Parsa A, Pattaro C, Pei Y, Pollak M, Rhee E, Sanna-Cherchi S, Savige J, Sayer J, Scolari F, Sedor J, Sim X, Somlo S, Susztak K, Tayo B, Torra R, van Eerde A, Weinstock A, Winkler C, Wuttke M, Zhang H, King J, Cheung M, Jadoul M, Winkelmayer W, Gharavi A. Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney International 2022, 101: 1126-1141. PMID: 35460632, PMCID: PMC9922534, DOI: 10.1016/j.kint.2022.03.019.
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.
Renal plasticity revealed through reversal of polycystic kidney disease in miceDong K, Zhang C, Tian X, Coman D, Hyder F, Ma M, Somlo S. Renal plasticity revealed through reversal of polycystic kidney disease in mice. Nature Genetics 2021, 53: 1649-1663. PMID: 34635846, PMCID: PMC9278957, DOI: 10.1038/s41588-021-00946-4.
A polycystin-2 protein with modified channel properties leads to an increased diameter of renal tubules and to renal cystsGrosch M, Brunner K, Ilyaskin AV, Schober M, Staudner T, Schmied D, Stumpp T, Schmidt KN, Madej MG, Pessoa TD, Othmen H, Kubitza M, Osten L, de Vries U, Mair MM, Somlo S, Moser M, Kunzelmann K, Ziegler C, Haerteis S, Korbmacher C, Witzgall R. A polycystin-2 protein with modified channel properties leads to an increased diameter of renal tubules and to renal cysts. Journal Of Cell Science 2021, 134: jcs259013. PMID: 34345895, PMCID: PMC8435292, DOI: 10.1242/jcs.259013.
FC 008INTERDEPENDENT REGULATION OF POLYCYSTIN EXPRESSION INFLUENCES STARVATION-INDUCED AUTOPHAGY AND CELL DEATHDecuypere J, Van Giel D, Janssens P, Dong K, Somlo S, Cai Y, Mekahli D, Vennekens R. FC 008INTERDEPENDENT REGULATION OF POLYCYSTIN EXPRESSION INFLUENCES STARVATION-INDUCED AUTOPHAGY AND CELL DEATH. Nephrology Dialysis Transplantation 2021, 36: gfab125.001. DOI: 10.1093/ndt/gfab125.001.
Restoration of proximal tubule flow-activated transport prevents cyst growth in polycystic kidney diseaseDu Z, Tian X, Ma M, Somlo S, Weinstein AM, Wang T. Restoration of proximal tubule flow-activated transport prevents cyst growth in polycystic kidney disease. JCI Insight 2021, 6: e146041. PMID: 33886508, PMCID: PMC8262298, DOI: 10.1172/jci.insight.146041.
Adult Inactivation of the Recessive Polycystic Kidney Disease Gene Causes Polycystic Liver Disease.Besse W, Roosendaal C, Tuccillo L, Roy SG, Gallagher AR, Somlo S. Adult Inactivation of the Recessive Polycystic Kidney Disease Gene Causes Polycystic Liver Disease. Kidney360 2020, 1: 1068-1076. PMID: 33554127, PMCID: PMC7861569, DOI: 10.34067/kid.0002522020.
Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney DiseaseZhang C, Balbo B, Ma M, Zhao J, Tian X, Kluger Y, Somlo S. Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney Disease. Journal Of The American Society Of Nephrology 2020, 32: 41-51. PMID: 33046531, PMCID: PMC7894654, DOI: 10.1681/asn.2020040511.
Loss of Cilia Does Not Slow Liver Disease Progression in Mouse Models of Autosomal Recessive Polycystic Kidney Disease.Gallagher AR, Somlo S. Loss of Cilia Does Not Slow Liver Disease Progression in Mouse Models of Autosomal Recessive Polycystic Kidney Disease. Kidney360 2020, 1: 962-968. PMID: 33829210, PMCID: PMC8023589, DOI: 10.34067/kid.0001022019.
Advancing Nephrology: Division Leaders Advise ASNBraden GL, Chapman A, Ellison DH, Gadegbeku CA, Gurley SB, Igarashi P, Kelepouris E, Moxey-Mims MM, Okusa MD, Plumb TJ, Quaggin SE, Salant DJ, Segal MS, Shankland SJ, Somlo S. Advancing Nephrology: Division Leaders Advise ASN. Clinical Journal Of The American Society Of Nephrology 2020, 16: 319-327. PMID: 32792352, PMCID: PMC7863658, DOI: 10.2215/cjn.01550220.
Large Deletions in GANAB and SEC63 Explain 2 Cases of Polycystic Kidney and Liver DiseaseWilson EM, Choi J, Torres VE, Somlo S, Besse W. Large Deletions in GANAB and SEC63 Explain 2 Cases of Polycystic Kidney and Liver Disease. Kidney International Reports 2020, 5: 727-731. PMID: 32405593, PMCID: PMC7210741, DOI: 10.1016/j.ekir.2020.01.009.
Disrupting polycystin-2 EF hand Ca2+ affinity does not alter channel function or contribute to polycystic kidney diseaseVien TN, Ng LCT, Smith JM, Dong K, Krappitz M, Gainullin VG, Fedeles S, Harris PC, Somlo S, DeCaen PG. Disrupting polycystin-2 EF hand Ca2+ affinity does not alter channel function or contribute to polycystic kidney disease. Journal Of Cell Science 2020, 133: jcs255562. PMID: 33199522, PMCID: PMC7774883, DOI: 10.1242/jcs.255562.
Collagen IV Gene Mutations in Adults With Bilateral Renal Cysts and CKDGulati A, Sevillano AM, Praga M, Gutierrez E, Alba I, Dahl NK, Besse W, Choi J, Somlo S. Collagen IV Gene Mutations in Adults With Bilateral Renal Cysts and CKD. Kidney International Reports 2019, 5: 103-108. PMID: 31922066, PMCID: PMC6943786, DOI: 10.1016/j.ekir.2019.09.004.
Cell-Autonomous Hedgehog Signaling Is Not Required for Cyst Formation in Autosomal Dominant Polycystic Kidney DiseaseMa M, Legué E, Tian X, Somlo S, Liem KF. Cell-Autonomous Hedgehog Signaling Is Not Required for Cyst Formation in Autosomal Dominant Polycystic Kidney Disease. Journal Of The American Society Of Nephrology 2019, 30: 2103-2111. PMID: 31451534, PMCID: PMC6830786, DOI: 10.1681/asn.2018121274.
ALG9 Mutation Carriers Develop Kidney and Liver CystsBesse W, Chang AR, Luo JZ, Triffo WJ, Moore BS, Gulati A, Hartzel DN, Mane S, Center R, Torres VE, Somlo S, Mirshahi T. ALG9 Mutation Carriers Develop Kidney and Liver Cysts. Journal Of The American Society Of Nephrology 2019, 30: 2091-2102. PMID: 31395617, PMCID: PMC6830805, DOI: 10.1681/asn.2019030298.
Glutamine metabolism via glutaminase 1 in autosomal-dominant polycystic kidney diseaseSoomro I, Sun Y, Li Z, Diggs L, Hatzivassiliou G, Thomas A, Rais R, Parker S, Slusher B, Kimmelman A, Somlo S, Skolnik E. Glutamine metabolism via glutaminase 1 in autosomal-dominant polycystic kidney disease. Nephrology Dialysis Transplantation 2019, 35: 1824-1824. PMID: 31329939, PMCID: PMC7538233, DOI: 10.1093/ndt/gfz109.
Spliced XBP1 Rescues Renal Interstitial Inflammation Due to Loss of Sec63 in Collecting DuctsIshikawa Y, Fedeles S, Marlier A, Zhang C, Gallagher AR, Lee AH, Somlo S. Spliced XBP1 Rescues Renal Interstitial Inflammation Due to Loss of Sec63 in Collecting Ducts. Journal Of The American Society Of Nephrology 2019, 30: 443-459. PMID: 30745418, PMCID: PMC6405156, DOI: 10.1681/asn.2018060614.
Mcp1 Promotes Macrophage-Dependent Cyst Expansion in Autosomal Dominant Polycystic Kidney DiseaseCassini MF, Kakade VR, Kurtz E, Sulkowski P, Glazer P, Torres R, Somlo S, Cantley LG. Mcp1 Promotes Macrophage-Dependent Cyst Expansion in Autosomal Dominant Polycystic Kidney Disease. Journal Of The American Society Of Nephrology 2018, 29: 2471-2481. PMID: 30209078, PMCID: PMC6171277, DOI: 10.1681/asn.2018050518.
TREX1 Mutation Causing Autosomal Dominant Thrombotic Microangiopathy and CKD—A Novel PresentationGulati A, Bale AE, Dykas DJ, Bia MJ, Danovitch GM, Moeckel GW, Somlo S, Dahl NK. TREX1 Mutation Causing Autosomal Dominant Thrombotic Microangiopathy and CKD—A Novel Presentation. American Journal Of Kidney Diseases 2018, 72: 895-899. PMID: 29941221, DOI: 10.1053/j.ajkd.2018.05.006.
Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney DiseaseGall E, Olson RJ, Besse W, Heyer CM, Gainullin VG, Smith JM, Audrézet MP, Hopp K, Porath B, Shi B, Baheti S, Senum SR, Arroyo J, Madsen CD, Férec C, Joly D, Jouret F, Fikri-Benbrahim O, Charasse C, Coulibaly JM, Yu AS, Khalili K, Pei Y, Somlo S, Le Meur Y, Torres VE, Group G, Group T, Disease T, Harris PC. Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease. American Journal Of Human Genetics 2018, 102: 832-844. PMID: 29706351, PMCID: PMC5986722, DOI: 10.1016/j.ajhg.2018.03.013.
Genomic Analysis to Avoid Misdiagnosis of Adults With Bilateral Renal Cysts.Gulati A, Bae KT, Somlo S, Watnick T. Genomic Analysis to Avoid Misdiagnosis of Adults With Bilateral Renal Cysts. Annals Of Internal Medicine 2018, 169: 130-131. PMID: 29582070, PMCID: PMC7196958, DOI: 10.7326/l17-0644.
Polycystin-2-dependent control of cardiomyocyte autophagyCriollo A, Altamirano F, Pedrozo Z, Schiattarella GG, Li DL, Rivera-Mejías P, Sotomayor-Flores C, Parra V, Villalobos E, Battiprolu PK, Jiang N, May HI, Morselli E, Somlo S, de Smedt H, Gillette TG, Lavandero S, Hill JA. Polycystin-2-dependent control of cardiomyocyte autophagy. Journal Of Molecular And Cellular Cardiology 2018, 118: 110-121. PMID: 29518398, DOI: 10.1016/j.yjmcc.2018.03.002.
Glutamine metabolism via glutaminase 1 in autosomal-dominant polycystic kidney diseaseSoomro I, Sun Y, Li Z, Diggs L, Hatzivassiliou G, Thomas AG, Rais R, Parker SJ, Slusher BS, Kimmelman AC, Somlo S, Skolnik EY. Glutamine metabolism via glutaminase 1 in autosomal-dominant polycystic kidney disease. Nephrology Dialysis Transplantation 2018, 33: 1343-1353. PMID: 29420817, PMCID: PMC6070111, DOI: 10.1093/ndt/gfx349.
A noncoding variant in GANAB explains isolated polycystic liver disease (PCLD) in a large familyBesse W, Choi J, Ahram D, Mane S, Sanna‐Cherchi S, Torres V, Somlo S. A noncoding variant in GANAB explains isolated polycystic liver disease (PCLD) in a large family. Human Mutation 2018, 39: 378-382. PMID: 29243290, PMCID: PMC5805583, DOI: 10.1002/humu.23383.
Ganetespib limits ciliation and cystogenesis in autosomal‐dominant polycystic kidney disease (ADPKD)Nikonova AS, Deneka AY, Kiseleva AA, Korobeynikov V, Gaponova A, Serebriiskii IG, Kopp MC, Hensley HH, Seeger‐Nukpezah T, Somlo S, Proia DA, Golemis EA. Ganetespib limits ciliation and cystogenesis in autosomal‐dominant polycystic kidney disease (ADPKD). The FASEB Journal 2018, 32: 2735-2746. PMID: 29401581, PMCID: PMC5901382, DOI: 10.1096/fj.201700909r.
Adenylyl cyclase 5 deficiency reduces renal cyclic AMP and cyst growth in an orthologous mouse model of polycystic kidney diseaseWang Q, Cobo-Stark P, Patel V, Somlo S, Han PL, Igarashi P. Adenylyl cyclase 5 deficiency reduces renal cyclic AMP and cyst growth in an orthologous mouse model of polycystic kidney disease. Kidney International 2017, 93: 403-415. PMID: 29042084, PMCID: PMC5794572, DOI: 10.1016/j.kint.2017.08.005.
Isolated polycystic liver disease genes define effectors of polycystin-1 functionBesse W, Dong K, Choi J, Punia S, Fedeles SV, Choi M, Gallagher AR, Huang EB, Gulati A, Knight J, Mane S, Tahvanainen E, Tahvanainen P, Sanna-Cherchi S, Lifton RP, Watnick T, Pei YP, Torres VE, Somlo S. Isolated polycystic liver disease genes define effectors of polycystin-1 function. Journal Of Clinical Investigation 2017, 127: 3558-3558. PMID: 28862642, PMCID: PMC5669574, DOI: 10.1172/jci96729.
Whole exome sequencing: a state-of-the-art approach for defining (and exploring!) genetic landscapes in pediatric nephrologyGulati A, Somlo S. Whole exome sequencing: a state-of-the-art approach for defining (and exploring!) genetic landscapes in pediatric nephrology. Pediatric Nephrology 2017, 33: 745-761. PMID: 28660367, DOI: 10.1007/s00467-017-3698-0.
Isolated polycystic liver disease genes define effectors of polycystin-1 functionBesse W, Dong K, Choi J, Punia S, Fedeles SV, Choi M, Gallagher AR, Huang EB, Gulati A, Knight J, Mane S, Tahvanainen E, Tahvanainen P, Sanna-Cherchi S, Lifton RP, Watnick T, Pei YP, Torres VE, Somlo S. Isolated polycystic liver disease genes define effectors of polycystin-1 function. Journal Of Clinical Investigation 2017, 127: 1772-1785. PMID: 28375157, PMCID: PMC5409105, DOI: 10.1172/jci90129.
Ciliary Mechanisms of Cyst Formation in Polycystic Kidney DiseaseMa M, Gallagher AR, Somlo S. Ciliary Mechanisms of Cyst Formation in Polycystic Kidney Disease. Cold Spring Harbor Perspectives In Biology 2017, 9: a028209. PMID: 28320755, PMCID: PMC5666631, DOI: 10.1101/cshperspect.a028209.
The polycystins are modulated by cellular oxygen-sensing pathways and regulate mitochondrial functionPadovano V, Kuo IY, Stavola LK, Aerni HR, Flaherty BJ, Chapin HC, Ma M, Somlo S, Boletta A, Ehrlich BE, Rinehart J, Caplan MJ. The polycystins are modulated by cellular oxygen-sensing pathways and regulate mitochondrial function. Molecular Biology Of The Cell 2016, 28: 261-269. PMID: 27881662, PMCID: PMC5231895, DOI: 10.1091/mbc.e16-08-0597.
Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cellsde Stephanis L, Bonon A, Varani K, Lanza G, Gafà R, Pinton P, Pema M, Somlo S, Boletta A, Aguiari G. Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cells. Clinical And Experimental Nephrology 2016, 21: 203-211. PMID: 27278932, PMCID: PMC5496448, DOI: 10.1007/s10157-016-1289-1.
Deletion of ADP Ribosylation Factor-Like GTPase 13B Leads to Kidney CystsLi Y, Tian X, Ma M, Jerman S, Kong S, Somlo S, Sun Z. Deletion of ADP Ribosylation Factor-Like GTPase 13B Leads to Kidney Cysts. Journal Of The American Society Of Nephrology 2016, 27: 3628-3638. PMID: 27153923, PMCID: PMC5118478, DOI: 10.1681/asn.2015091004.
mTORC1-mediated inhibition of polycystin-1 expression drives renal cyst formation in tuberous sclerosis complexPema M, Drusian L, Chiaravalli M, Castelli M, Yao Q, Ricciardi S, Somlo S, Qian F, Biffo S, Boletta A. mTORC1-mediated inhibition of polycystin-1 expression drives renal cyst formation in tuberous sclerosis complex. Nature Communications 2016, 7: 10786. PMID: 26931735, PMCID: PMC4778067, DOI: 10.1038/ncomms10786.
Human Polycystin-2 Transgene Dose-Dependently Rescues ADPKD Phenotypes in Pkd2 Mutant MiceLi A, Tian X, Zhang X, Huang S, Ma Y, Wu D, Moeckel G, Somlo S, Wu G. Human Polycystin-2 Transgene Dose-Dependently Rescues ADPKD Phenotypes in Pkd2 Mutant Mice. American Journal Of Pathology 2015, 185: 2843-2860. PMID: 26435415, PMCID: PMC4607765, DOI: 10.1016/j.ajpath.2015.06.014.
Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in PodocytesHassan H, Tian X, Inoue K, Chai N, Liu C, Soda K, Moeckel G, Tufro A, Lee AH, Somlo S, Fedeles S, Ishibe S. Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes. Journal Of The American Society Of Nephrology 2015, 27: 1055-1065. PMID: 26303067, PMCID: PMC4814187, DOI: 10.1681/asn.2015020191.
Phosphoinositide 3-Kinase-C2α Regulates Polycystin-2 Ciliary Entry and Protects against Kidney Cyst FormationFranco I, Margaria JP, De Santis MC, Ranghino A, Monteyne D, Chiaravalli M, Pema M, Campa CC, Ratto E, Gulluni F, Perez-Morga D, Somlo S, Merlo GR, Boletta A, Hirsch E. Phosphoinositide 3-Kinase-C2α Regulates Polycystin-2 Ciliary Entry and Protects against Kidney Cyst Formation. Journal Of The American Society Of Nephrology 2015, 27: 1135-1144. PMID: 26271513, PMCID: PMC4814170, DOI: 10.1681/asn.2014100967.
The Future of Polycystic Kidney Disease Research—As Seen By the 12 Kaplan AwardeesAntignac C, Calvet JP, Germino GG, Grantham JJ, Guay-Woodford LM, Harris PC, Hildebrandt F, Peters DJ, Somlo S, Torres VE, Walz G, Zhou J, Yu AS. The Future of Polycystic Kidney Disease Research—As Seen By the 12 Kaplan Awardees. Journal Of The American Society Of Nephrology 2015, 26: 2081-2095. PMID: 25952256, PMCID: PMC4552123, DOI: 10.1681/asn.2014121192.
Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein StabilityPedrozo Z, Criollo A, Battiprolu PK, Morales CR, Contreras-Ferrat A, Fernández C, Jiang N, Luo X, Caplan MJ, Somlo S, Rothermel BA, Gillette TG, Lavandero S, Hill JA. Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability. Circulation 2015, 131: 2131-2142. PMID: 25888683, PMCID: PMC4470854, DOI: 10.1161/circulationaha.114.013537.
Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severityFedeles SV, So JS, Shrikhande A, Lee SH, Gallagher AR, Barkauskas CE, Somlo S, Lee AH. Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity. Journal Of Clinical Investigation 2015, 125: 1955-1967. PMID: 25844898, PMCID: PMC4463201, DOI: 10.1172/jci78863.
The imperative to invest in science has never been greaterCarethers J, Coughlin S, Diamond B, Erzurum S, Fried L, Jameson J, Kaushansky K, Klotman M, Lemon S, Mitchell B, Rothman P, Sawyers C, Seidman C, Somlo S. The imperative to invest in science has never been greater. Journal Of Clinical Investigation 2014, 124: 5085-5085. PMCID: PMC4347232, DOI: 10.1172/jci79469.
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.
The Kidney Research National Dialogue: Gearing Up to Move ForwardBonventre JV, Boulware LE, Dember LM, Freedman BI, Furth SL, Holzman LB, Ketchum CJ, Little MH, Mehrotra R, Moe SM, Sands JM, Sedor JR, Somlo S, Star RA, Rys-Sikora KE. The Kidney Research National Dialogue: Gearing Up to Move Forward. Clinical Journal Of The American Society Of Nephrology 2014, 9: 1806-1811. PMID: 25225184, PMCID: PMC4186514, DOI: 10.2215/cjn.07310714.
The imperative to invest in science has never been greaterCarethers JM, Coughlin S, Diamond B, Erzurum S, Fried LP, Jameson JL, Kaushansky K, Klotman ME, Lemon S, Mitchell B, Rothman P, Sawyers C, Seidman C, Somlo S. The imperative to invest in science has never been greater. Journal Of Clinical Investigation 2014, 124: 3680-3681. PMID: 25180532, PMCID: PMC4151225, DOI: 10.1172/jci77894.
Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney diseaseLee SH, Somlo S. Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease. Kidney Research And Clinical Practice 2014, 33: 73-78. PMID: 26877954, PMCID: PMC4714135, DOI: 10.1016/j.krcp.2014.05.002.
Filling the Holes in Cystic Kidney Disease ResearchGuay-Woodford LM, Henske E, Igarashi P, Perrone RD, Reed-Gitomer B, Somlo S, Torres VE, Ketchum CJ, Star RA, Flessner MF, Rasooly RS. Filling the Holes in Cystic Kidney Disease Research. Clinical Journal Of The American Society Of Nephrology 2014, 9: 1799-1801. PMID: 24903391, PMCID: PMC4186512, DOI: 10.2215/cjn.03410414.
N-Glycosylation Determines the Abundance of the Transient Receptor Potential Channel TRPP2*Hofherr A, Wagner C, Fedeles S, Somlo S, Köttgen M. N-Glycosylation Determines the Abundance of the Transient Receptor Potential Channel TRPP2*. Journal Of Biological Chemistry 2014, 289: 14854-14867. PMID: 24719335, PMCID: PMC4031537, DOI: 10.1074/jbc.m114.562264.
Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease (690.2)Chatsudthipong V, Yuajit C, Muanprasat C, Kittayaruksakul S, Fedeles S, Gallagher A, Somlo S. Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease (690.2). The FASEB Journal 2014, 28 DOI: 10.1096/fasebj.28.1_supplement.690.2.
Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney diseaseYuajit C, Muanprasat C, Gallagher AR, Fedeles SV, Kittayaruksakul S, Homvisasevongsa S, Somlo S, Chatsudthipong V. Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease. Biochemical Pharmacology 2014, 88: 412-421. PMID: 24518257, DOI: 10.1016/j.bcp.2014.01.038.
Polycystin-1: a master regulator of intersecting cystic pathwaysFedeles SV, Gallagher AR, Somlo S. Polycystin-1: a master regulator of intersecting cystic pathways. Trends In Molecular Medicine 2014, 20: 251-260. PMID: 24491980, PMCID: PMC4008641, DOI: 10.1016/j.molmed.2014.01.004.
Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney diseaseMa M, Tian X, Igarashi P, Pazour GJ, Somlo S. Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease. Nature Genetics 2013, 45: 1004-1012. PMID: 23892607, PMCID: PMC3758452, DOI: 10.1038/ng.2715.
miR-17∼92 miRNA cluster promotes kidney cyst growth in polycystic kidney diseasePatel V, Williams D, Hajarnis S, Hunter R, Pontoglio M, Somlo S, Igarashi P. miR-17∼92 miRNA cluster promotes kidney cyst growth in polycystic kidney disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 10765-10770. PMID: 23759744, PMCID: PMC3696812, DOI: 10.1073/pnas.1301693110.
Mechanoprotection by Polycystins Against Apoptosis is Mediated Through the Opening of Stretch‐Activated K2P ChannelsDuprat F, Peyronnet R, Sharif‐Naeini R, Folgering J, Arhatte M, Jodar M, Boustany C, Gallian C, Tauc M, Duranton C, Rubera I, Lesage F, Pei Y, Peters D, Somlo S, Sachs F, Patel A, Honoré E. Mechanoprotection by Polycystins Against Apoptosis is Mediated Through the Opening of Stretch‐Activated K2P Channels. The FASEB Journal 2013, 27: 912.2-912.2. DOI: 10.1096/fasebj.27.1_supplement.912.2.
Chapter 80 Autosomal Dominant Polycystic Kidney DiseaseSomlo S, Torres V, Caplan M. Chapter 80 Autosomal Dominant Polycystic Kidney Disease. 2013, 2645-2688. DOI: 10.1016/b978-0-12-381462-3.00080-x.
Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferationAguiari G, Bizzarri F, Bonon A, Mangolini A, Magri E, Pedriali M, Querzoli P, Somlo S, Harris PC, Catizone L, del Senno L. Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferation. Journal Of Molecular Medicine 2012, 90: 1267-1282. PMID: 22570239, PMCID: PMC4028691, DOI: 10.1007/s00109-012-0902-3.
Mechanoprotection by Polycystins against Apoptosis Is Mediated through the Opening of Stretch-Activated K2P ChannelsPeyronnet R, Sharif-Naeini R, Folgering JH, Arhatte M, Jodar M, Boustany C, Gallian C, Tauc M, Duranton C, Rubera I, Lesage F, Pei Y, Peters DJ, Somlo S, Sachs F, Patel A, Honoré E, Duprat F. Mechanoprotection by Polycystins against Apoptosis Is Mediated through the Opening of Stretch-Activated K2P Channels. Cell Reports 2012, 1: 241-250. PMID: 22832196, PMCID: PMC3437542, DOI: 10.1016/j.celrep.2012.01.006.
Evaluation of urine biomarkers of kidney injury in polycystic kidney diseaseParikh CR, Dahl NK, Chapman AB, Bost JE, Edelstein CL, Comer DM, Zeltner R, Tian X, Grantham JJ, Somlo S. Evaluation of urine biomarkers of kidney injury in polycystic kidney disease. Kidney International 2012, 81: 784-790. PMID: 22258321, PMCID: PMC3319327, DOI: 10.1038/ki.2011.465.
Different effects of Sec61α, Sec62 and Sec63 depletion on transport of polypeptides into the endoplasmic reticulum of mammalian cellsLang S, Benedix J, Fedeles SV, Schorr S, Schirra C, Schäuble N, Jalal C, Greiner M, Haßdenteufel S, Tatzelt J, Kreutzer B, Edelmann L, Krause E, Rettig J, Somlo S, Zimmermann R, Dudek J. Different effects of Sec61α, Sec62 and Sec63 depletion on transport of polypeptides into the endoplasmic reticulum of mammalian cells. Journal Of Cell Science 2012, 125: 1958-1969. PMID: 22375059, PMCID: PMC4074215, DOI: 10.1242/jcs.096727.

Clinical Trials

Conditions	Study Title
Diseases of the Cardiovascular System; Diseases of the Kidney & Urinary Tract; Genetics - Adult	Genetic Determinants of Aneurysms in Autosomal Dominant Polycystic Kidney Disease
Diseases of the Digestive System - Liver; Genetics - Adult	Genetic Studies of Polycystic Livers

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Stefan Somlo, MD

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