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Polycystic Kidney Disease

What is Polycystic Kidney Disease?

Polycystic kidney diseases (PKD) are a group of disorders characterized by dilated segments of renal tubules that pinch off to form fluid-filled structures or cysts. As cysts gradually enlarge, they compress normal kidney tissue and prevent it from functioning normally.

This results in high blood pressure and kidney failure, which may require dialysis or transplantation. As kidney cysts enlarge, they also can cause a number of other problems including pain, infection and hemorrhage. Kidney stones are also more common in individuals with cystic kidney disease.

One form of PKD, called autosomal dominant polycystic kidney disease (ADPKD), is the most common single-gene disorder that causes kidney failure. It is estimated that approximately 600,000 individuals in the United States alone have ADPKD. ADPKD is the fourth-most common cause of kidney failure in the U.S., and occurs in people of all races and ethnicities.

The Polycystic Kidney Diseases

A number of acquired and genetic diseases can result in polycystic kidney. The various forms differ with respect to the way in which they are inherited (autosomal dominant, autosomal recessive or X-linked); the range of renal and extra-renal manifestations that accompany the cystic disease; the age at which renal failure most commonly presents (childhood vs. adult); and the mutant gene responsible for causing the disorder.

Some of the disorders associated with kidney cysts and/or liver cysts:

Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Individuals with one mutant copy of the gene (PKD1 or PKD2) develop the disease. A parent with the disease has a 50 percent chance of passing the mutant gene to his/her children. ADPKD is associated with slowly progressive cystic kidney disease that results in kidney failure in about 50 percent of affected individuals. The age at onset of kidney failure is variable and 50 percent of individuals with ADPKD develop kidney failure by age 60. Hypertension, cerebral aneurysms, cardiac valvular abnormalities, liver cysts, kidney stones, and aortic aneurysms are important complications.

Autosomal Dominant Polycystic Liver Disease (PLD)
This is an autosomal dominant disorder that is biologically related to ADPKD. Two genes so far are known to cause PLD (Sec 63 and PRKCSH) but there are others that have not yet been identified. Individuals with PLD develop liver cysts and may have a small number of kidney cysts but they don’t develop kidney failure.

Autosomal Recessive Polycystic Kidney Disease (ARPKD; also called PKHD1)
This is a relatively rare disorder occurring in 1 in 20,000 individuals. The disease results when both copies of the fibrocystin gene on chromosome 6 are mutated. Parents are carriers and unaffected. Affected offspring inherit a mutant copy from each parent. A couple in which both partners are carriers for the disease have a 25 percent chance of having a child with the disease. The disease usually presents during infancy or in childhood, with up to 50 percent of affected children dying in the first year of life. Older children and adults may have severe liver disease requiring transplantation.

This is a collection of recessive diseases in which parents are unaffected carriers and offspring develop kidney disease between infancy and adolescence. Some forms of the disease are associated with eye abnormalities.

Bardet-Biedl Syndrome
This is a group of recessive disorders that present with eye disease (retinopathy), obesity, hypogonadism, a variety of kidney abnormalities, extra digits on the hand or feet and mental retardation.

Medullary Cystic Disease
This is an autosomal dominant disease caused by mutations in the gene for uromodulin on chromosome 16. Recently, mutations in the mucin gene on chromosome 1 were also shown to be associated with medullary cystic disease. Although individuals do have some kidney cysts, interstitial scarring of the kidneys is prominent and kidneys tend to be small. Renal failure typically develops in adulthood; other complications include high uric acid levels and gout.

Tuberous Sclerosis
This is an autosomal dominant disease that is caused by mutations in genes called TSC1 or TSC2. Tuberous sclerosis is associated with benign tumors in multiple organs. Kidney cancer is a rare complication of TSC. Individuals with TSC may have a few renal cysts but a subset can present with polycystic kidney disease resembling ADPKD. This may be caused by mutations that affect both genes.

Von Hippel Lindau Syndrome
This is an autosomal dominant disorder that presents with tumors in the nervous system, adrenal gland tissue, kidney cancer and kidney cysts.

Is There a Treatment for PKD?

There are presently no treatments, but this is an area of active research. A recent study in the New England Journal of Medicine reported the results of a randomized, double-blind placebo-controlled trial using Tolvaptan (a blocker of the vasopressin receptor) in a large group of participants with autosomal dominant polycystic kidney disease. The concept of vasopressin blockade to slow PKD progression is supported by numerous studies in PKD mouse models.

There are other experimental drugs being tested in mouse models of PKD and some in clinical trials. In addition, healthcare providers continue to manage complications of the various forms of the disease, such as treating hypertension or infections.

PKD Care

Dr. Terry Watnick is the Director of the University of Maryland Inherited Renal Disease Clinic. The clinic forms the translational arm of the PKD group at the University of Maryland and receives national and international referrals of patients who require diagnosis and/or management of complicated cystic kidney disease.

Dr. Watnick has served as a principal Investigator for TEMPO, a multicenter trial that tested the efficacy of Tolvaptan (a vasopressin receptor 2 antagonist) in slowing renal disease progression in ADPKD.

The team at the University of Maryland provides multidisciplinary expertise in many subspecialty fields involved in treating ADPKD complications, including Gastroenterology and Hepatology, Neurosurgery, and Interventional Radiology. The University of Maryland Comprehensive Transplant Program performs nearly 300 kidney transplants per year and is one of the largest programs in the country.

PKD Research

PKD poses special challenges for investigators seeking therapies. It is frequently a slowly progressive disease that evolves over decades. The risk of a therapy must be less than the potential benefit. The University of Maryland team and collaborators are tackling the problem on two parallel tracks. In the first, the investigators seek to define the pathophysiology of the disease as a means of identifying steps for possible intervention. The second approach is aimed at determining the normal functions of the PKD proteins, seeking to identify ways that their activity may be replaced in disease tissue.

Although we have made significant progress the first human PKD gene was discovered, significant questions remain. We still do not know why some patients develop severe disease or aneurysms while family members with the same mutation do not. Are there other underlying genetic factors that determine the severity of disease or its rate of progression? Why do some mutations result in severe disease more frequently? How does loss of PKD proteins cause the vascular manifestations that are observed? How do dietary or lifestyle factors affect progression of disease? Do any of the experimental therapies used in other forms of mouse PKD work in the form that most commonly affects humans? Future NIH clinical studies propose to use changes in the amount of kidney tissue as a means of assessing response to therapy. Is this really a suitable surrogate marker for functional response?

  • Baltimore PKD Research and Clinical Core Center: The University of Maryland is home to one of four NIH-sponsored PKD Research and Translation Core Centers. The Center is comprised of four biomedical Cores that are charged with developing and distributing state-of-the-art research reagents to a national and international group of PKD researchers. The goal of the Center is to foster a greater understanding of the fundamental aspects of PKD biology. Learn more
  • Identify PKD signaling pathways: Most PKD genes encode proteins that sit on the surface of cells and transmit information across the cell boundary into the cell interior. The cell uses this information to respond to its environment. In PKD, the cell is either unable to acquire this information because the sensor is defective or is unable to respond properly to the signal. University of Maryland researchers are seeking to define the types of information that PKD proteins sense and the pathways inside the cell that PKD proteins regulate.
  • Characterize the Cellular Biology of PKD Proteins: Many PKD proteins are found in primary cilia, a small hair-like structure on the surface of the cell that is required for proper cell function. Polycystic kidney disease results when cilia aren’t properly formed or when signaling proteins don’t make it to the primary cilia. University of Maryland Investigators are using a variety of tools to study how PKD proteins reach the cilia in kidney cells. One of our investigators has found that a biochemical reaction that cuts the PKD1 protein is required for PKD1 and PKD2 to reach the cilia.
  • Determine how PKD proteins help to preserve normal blood vessel structure and function: The cardiovascular complications of PKD are an important cause of premature death and morbidity. Studies of patients with ADPKD and of mouse models of human ADPKD show that PKD proteins are essential for normal blood vessels. Both humans and mice with PKD mutations develop hemorrhages. In pilot studies done by University of Maryland nephrology faculty in collaboration with Dr. Hal Dietz of the Howard Hughes Institute at JHU, they have identified a signaling pathway that may be altered in ADPKD. The proposed studies aim to understand this process in the hope that future treatments may be directed at preventing these complications.
  • Engineer and manipulate mouse models of human PKD: The University of Maryland team has used transgenic technologies to produce mice with cystic kidney disease very similar to the disorder that affects humans (both ADPKD and ARPKD). These powerful models can be used to test various therapies for PKD in a cost-effective manner before they are tested in humans.
  • Determine the function of the ARPKD protein (called fibrocystin or polyductin): The University of Maryland team has recently developed animal and cell culture systems that can be used to model the human disease and the ARPKD protein’s function. Preliminary studies at University of Maryland suggest that fibrocystin and the polycystins may work together as a complex to ensure proper formation of the kidney tubule.
  • Use Simple Systems to study PKD Proteins: We have developed a fruit fly with mutations in the PKD2 gene. University of Maryland investigators are using this simple system to examine how PKD proteins reach the tip of the cilium.
  • Longitudinal Cohort Study: Progression of autosomal dominant polycystic kidney disease to kidney failure is highly variable. A number of factors including age, genotype and incidence of cardiovascular disease determine how quickly the disorder progresses. Dr. Terry Watnick and Dr. Stephen Seliger, who together direct the Clinical and Translation Core of the Baltimore PKD Center, are collecting baseline data on a large cohort of individuals with ADPKD. The goal of the cohort study is to better understand the factors that influence PKD progression. In addition, this study will establish a high-quality biorepository with specimens collected under standardized conditions. This biorepository is expected be a valuable resource for PKD investigators. Learn more

PKD Publications

Authored by University of Maryland Nephrology Faculty Members.

  1. The American Polycystic Kidney Disease Consortium (APKD1): (Burn TJ, Connors TD, Dackowski WR, Petry LR, Van Raay TJ, Millholland JM, Venet M, Miller G, Hakim RH, Landes GM, Klinger KW, Qian F, Onuchic LF, Watnick T, Germino GG, Doggett N) The autosomal dominant polycystic kidney disease (PKD1) gene product contains a leucine-rich repeat. Hum Mol Genet, 4:575-582, 1995.
  2. Qian F*, Watnick TJ*, Onuchic LF, Germino GG. The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell, 87:979-987, 1996. (*Co-authors, listed alphabetically).
  3. Qian F, Germino FJ, Cai Y, Zhang X, Somlo S, Germino GG. PKD1 interacts with PKD2 through a probable coiled-coil domain. Nature Genetics, 16:179-183, 1997.
  4. Ibraghimov-Beskrovnaya O, Dackowski WR, Foggensteiner L, Coleman N, Thiru S, Petrey LR, Burn TC, Connors TD, Van Raay T, Bradley J, Qian F, Onuchic LF, Watnick TJ, Piontek K, Hakim RM, Germino GG, Landes GM, Sandford R, Klinger KW. Polycystin: in vitro synthesis, in vivo tissue expression and subcellular localization identifies a large membrane-associated protein. Proc Natl Acad Sci, USA, 94:6397-6402, 1997
  5. Watnick TJ, Piontek KB, Cordal TM, Weber H, Gandolph MA, Qian F, Lens XM, Neumann HPH, Germino GG. An unusual pattern of mutation in the replicated portion of PKD1 is revealed by use of a novel strategy for mutation detection. Hum Molec Genet, 6:1473-1481, 1997.
  6. Qian F, Germino GG. 'Mistakes Happen': Somatic mutation and disease. Am J Hum Genet, 61:1000-1005, 1997.
  7. Watnick TJ, Torres VE, Gandolph MA, Qian F, Onuchic LF, Klinger KW, Landes G, Germino GG. Somatic mutation in individual liver cysts supports a two hit model of cystogenesis in autosomal dominant polycystic kidney disease, type I. Molec Cell, 2:247-251, 1998.
  8. Watnick TJ, Torres VE, Gandolph MA, Weber H, Neumann HPH, Germino GG. Gene conversion may be an important cause of mutation in PKD1. Hum Mol Genet. 7:1239-43, 1998.
  9. Pei Y, Watnick T, He N, Wang K, Liang Y, Parfrey P, Germino G, St. George-Hyslop P. Somatic PKD2 mutations in individual kidney and liver cysts support a "two-hit" model of cystogenesis in type 2 autosomal dominant polycystic kidney disease. J Am Soc Nephrol, 10:1524-1529, 1999.
  10. Reynolds DM, Hayashi T, Cai Y, Veldhuisen B, Watnick TJ, Lens XM, Mochizuki T, Qian F, Fossdal R, Coto E, Wu G, Breuning MH, Germino GG, Peters DJM, Somlo S. Abberant splicing in the PKD2 gene as a cause of polycystic kidney disease. J Am Soc Nephrol, 10:2342-2351, 1999.
  11. Watnick T, Phakdeekitcharoen B, Johnson A, Gandolph M, Wang M, Briefel G, Klinger KW, Kimberling W, Gabow P, Germino GG. Mutation detection of PKD1 identifies a novel mutation common to three families with severe disease. Am J Hum Genet, 65:1561-1571, 1999.
  12. Watnick T, He N, Wang K, Liang Y, Parfrey P, Hefferton D, St. George-Hyslop P, *Germino G, *Pei Y. Somatic mutations of PKD1 in ADPKD2 cystic tissue suggests a possible pathogenic effect of trans-heterozygous mutations. Nat Genet, 25:143-144, 2000. (* = Co-correspondents)
  13. Hanaoka K, Qian F*, Boletta A, Bhunia A, Piontek K, Tsiokas L, Sukhatme VP, Germino GG, Guggino WB. Co-assembly of polycystin 1 and 2 produces unique cation permeable currents. Nature 408: 990-4, 2000. (*Co-first author)
  14. Phakdeekitcharoen B, Watnick TJ, Ahn C, Whang D-Y, Burkhard B, Germino GG. Thirteen novel mutations of the replicated region of PKD1 in an Asian population. Kidney International, 58:1400-1412, 2000.
  15. Boletta A, Qian F, Onuchic LF, Bhunia AK, Phakdeekitcharoen B, Hanaoka K, Guggino W, Monaco L, Germino GG. Polycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells. Molec Cell, 6:1267-1273, 2000.
  16. Pei Y, Paterson AD, Wang KR, Ne N, Hefferton D, Watnick T, Germino G, Parfrey P, Somlo S, St. George-Hyslop P. Bilineal disease and trans-heterozygotes in autosomal dominant polycystic kidney disease. Am J Human Genet, 68:355-363, 2001.
  17. Phakdeekitcharoen B, Watnick TJ, Germino GG. Mutation detection of entire duplicated part of PKD1 in genomic DNA sample. J Am Soc Nephrol, 12:955-963, 2001.
  18. Boletta A, Qian F, Onuchic LF, Bragonzi A, Cortese M, Courtoy PJ, Deen PM, Soria MR, Devuyst O, Monaco L, Germino GG. Biochemical characterization of bona fide polycystin-1 in vitro and in vivo. Am J Kid Dis, 38:1421-1429, 2001.
  19. Chauvet V, Qian F, Boute N, Cai Y, Phakdeekitcharoen B, Onuchic LF, Attie-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. Am J Pathol, 160:973-983, 2002.
  20. Bhunia AK, Piontek K, Boletta A, Liu L, Qian F, Xu P-N, Germino FJ, Germino GG. PKD1 induces p21waf1 and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell, 109:157-168, 2002.
  21. Qian F, Boletta A, Bhunia AK, Xu H, Liu L, Ahrabi AM, Watnick TJ, Zhou F, Germino GG. Cleavage of polycystin-1 requires the REJ domain and is disrupted by human ADPKD1-associated mutations. Proc Natl Acad Sci, USA, 99:16981-16986, 2002.
  22. Watnick T, Germino GG. From cilia to cyst. Nature Genet, 34:355-356, 2003.
  23. Watnick TJ, Jin Y, Matunis E, Kernan MJ, Montell C. A flagellar polycystin-2 homolog required for male fertility in Drosophila. Curr Biol, 13: 2179-2184, 2003
  24. Piontek KB, Huso DL, Grinberg A, Liu L, Bedja D, Zhao H, Gabrielson K, Qian F, Mei C, Westphal H, and Germino GG. A functional floxed allele of Pkd1 that can be conditionally inactivated in vivo. J Am Soc Nephrol, 15: 3035-43, 2004.
  25. Hackmann K, Markoff A, Qian F, Bogdanova N, Germino GG, Pennekamp P, Dworniczak B, Horst J, Gerke V. A splice form of polycystin-2, lacking exon 7, does not interact with polycystin-1. Hum Mol Genet, 14:3249-62, 2005.
  26. Qian F, Wei W, Germino GG, Oberhauser AF. The nanomechanics of polycystin-1 extracellular region. J Biol Chem, 280: 40723-30, 2005.
  27. Li Y, Wright JM, Qian F, Germino GG, Guggino WB. Polycystin 2 interacts with type I inositol 1,4,5- trisphosphate receptor to modulate intracellular Ca2+ signaling. J Biol Chem, 280: 41298-306. 2005.
  28. Ikeda M, Fong P, Cheng J, Boletta A, Qian F, Zhang X, Cai H, Germino GG, Guggino WB. A Regulatory Role of Polycystin-1 on Cystic Fibrosis Transmembrane Conductance Regulator Plasma Membrane Expression. Cell Physiol Biochem, 18:9-20, 2006.
  29. Boca M, Distefano G, Qian F, Bhunia AK, Germino GG, Boletta A. Polycystin-1 Induces Resistance to Apoptosis through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway. J Am Soc Nephrol,17: 637-47, 2006.
  30. Garcia-Gonzalez MA., Jones JG., Allen SK., Palatucci CM., Batish SD., Seltzer WK., Lan Z., Allen E., Qian F., Lens XM., Pei Y., Germino GG. and Watnick TJ. Evaluating the clinical utility of a molecular genetic test for polycystic kidney disease. Mol Genet Metab. 92:160-7, 2007.
  31. Garcia-Gonzalez MA, Menezes LF, Piontek KB, Kaimori J, Huso DL, Watnick T, Onuchic LF, Guay-Woodford LM, Germino GG. Genetic interaction studies link autosomal dominant and recessive polycystic kidney disease in a common pathway. Hum Molecular Genetics, 16: 1940-50, 2007.
  32. Tan PL, Barr T, Inglis PN, Mitsuma N, Huang SM, Garcia-Gonzalez MA, Bradley BA, Coforio S, Albrecht PJ, Watnick T, Germino GG, Beales PL, Caterina MJ, Leroux MR, Rice FL, Katsanis N. Loss of Bardet Biedl syndrome proteins causes defects in peripheral sensory innervation and function. Proc Natl Acad Sci, USA, 104:17524-17529, 2007.
  33. Wei W, Hackmann K, Xu H, Germino GG, and Qian F. Characterization of cis-autoproteolysis of polycystin-1, the product of human polycystic kidney disease 1 gene. J Biol Chem, 282:21729-37, 2007.
  34. Yu S, Hackmann K, Gao J, Piontek K, García-González MA, Menezes LF, Xu H, He X, Germino GG, Zuo J and Qian F. Essential role of proteolytic cleavage of polycystin-1 for kidney tubular structure. Proc Natl Acad Sci U S A, 104:18688-93, 2007.
  35. Köttgen M, Buchholz B, Garcia-Gonzalez MA, Kotsis F, Fu X, Doerken M, Boehlke C, Steffl D, Tauber R, Wegierski T, Nitschke R, Suzuki M, Kramer-Zucker A, Germino GG, Watnick T, Prenen J, Nilius B, Kuehn EW, Walz G. TRPP2 and TRPV4 form a polymodal sensory channel complex. J Cell Biol, 182: 437-47, 2008.
  36. Huang E, Samaniego M, McCune T, Melancon J, Montgomery R, Ugarte R, Kraus E, Womer K, Rabb H, Watnick T. DNA Testing for Live Kidney Donors at Risk for Autosomal Dominant Polycystic Kidney Disease. Transplantation, 87: 133-37, 2009.
  37. Hartman TR, Liu D, Zilfou JT, Robb V, Morrison T, Watnick T, Henske EP. The tuberous sclerosis proteins regulate the formation of the primary cilium via a rapamycin-insensitive and polycystin-1 independent pathway. Hum Mol Genet, 18: 151-63, 2009.
  38. Wodarczyk C, Rowe I, Chiaravalli M, Pema M, Qian F, Boletta A. A novel mouse model reveals that polycystin-1 deficiency in ependyma and choroid plexus results in dysfunctional cilia and hydrocephalus. PLoS One 4(9):e7137, 2009.
  39. Li Y, Santoso NG, Yu S, Woodward OM, Qian F, Guggino WB. Polycystin-1 interacts with IP3R to modulate intracellular Ca2+ signaling, with implications for polycystic kidney disease. J Biol Chem, 284: 36431-41, 2009.
  40. Nadella R, Blumer JB, Jia G, Kwon M, Akbulut T, Qian F, Sedlic F, Wakatsuki T, Sweeney Jr. WE, Wilson PD, Lanier SM, Park F. Increased Activator of G protein signaling 3 promotes epithelial cell proliferation in polycystic kidney disease. J Am Soc Nephrol, 21:1275-80, 2010.
  41. Woodward OM., Li Y., Yu S., GreenwellP., Wodarczyk C., Boletta A., Guggino WB and Qian F. Identification of a Polycystin-1 cleavage product, P100, that regulates store operated Ca2+ entry through interactions with STIM1. PLoS One, 23;5(8):e12305.31. 2010.
  42. Garcia-Gonzalez MA, Outeda P, Zhou Q, Zhou F, Menezes LF, Qian F, Huso DL, Germino GG, Piontek KB, Watnick T. Pkd1 and pkd2 are required for normal placental development. PLoS One. 5(9). pii: e12821.32, 2010.
  43. Kashtan CE, Segal Y, Flinter F, Makanjuola D, Gan J-S, Watnick T. Aortic Abnormalities in Males with Alport Syndrome. Nephrol Dial and Transplant, 11:3554-60, 2010.
  44. Watnick T, Germino G. The role of mTOR inhibitors in autosomal dominant polycystic kidney disease. New Engl. J of Med. 363: 879-81, 2010
  45. Shah S, Watnick T, Atta MG. Not All Renal Cysts Are Created Equal. Lancet 376:1024, 2010.
  46. Pei Y and Watnick T. Diagnosis and screening of autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis. 17: 140-52, 2010.
  47. Talbot JJ, Shillingford JM, Vasanth S, Doerr N, Mukherjee S, Kinter MT, Watnick T, Weimbs T. Polycystin-1 regulates STAT activity by a dual mechanism. Proc Natl Acad Sci, USA, 108:7985-90, 2011.
  48. Kottgen M, Hofherr A, Li W, Chu K, Cook S, Montell C, Watnick T. Drosophila Sperm Swim Backwards in the Female Reproductive Tract and Are Activated via TRPP2 Ion Channels. PLoS One. 6(5):e20031, 2011.
  49. Higashihara E, Torres VE, Chapman AB, Grantham JJ, Bae K, Watnick TJ, Horie S, Nutahara K, Ouyang J, Krasa HB, Czerwiec FS; TEMPO Formula and 156-05-002 Study Investigators. Tolvaptan in autosomal dominant polycystic kidney disease: three years experience. Clin J Am Soc Nephrol, 6: 2499-507, 2011.
  50. Schroder S, Fraternali F, Quan X, Scott DJ, Qian F., Pfuhl M. When a module is not a domain - the case of the REJ module and the redefinition of the architecture of polycystin-1. Biochem J, 435:651-60, 2011.
  51. Steigelman KA, Lelli A, Wu X, Gao J, Lin S, Piontek K, Wodarczyk C, Boletta A, Kim H, Qian F, Germino G, Géléoc GS, Holt JR, Zuo J. Polycystin-1 is required for stereocilia structure but not for mechanotransduction in inner ear hair cells. J Neurosci, 31:12241-50, 2011.
  52. Foy RL, Chitalia VC, Panchenko MV, Zeng L, Lopez D, Lee JW, Rana SV, Boletta A, Qian F, Tsiokas L, Piontek KB, Germino GG, Zhou MI, Cohen HT. Polycystin-1 regulates the stability and ubiquitination of transcription factor Jade-1. Hum Mol Genet. 21: 5456-71,2012.
  53. Pei Y, Lan Z, Wang K, Garcia-Gonzalez M, He N, Dicks E, Parfrey P, Germino G, Watnick T. A Missense Mutation in PKD1attenuates the severity of Renal Disease. Kidney Int. 81: 412-7, 2012.
  54. Kwon M, Pavlov TS, Nozu K, Rasmussen S, Ilatovskaya DV, Lerch-Gaggl A, North LM, Kim H, Qian F, Sweeney, WE Jr. Avner ED, Blumer JB, Staruschenko A, Park F. G protein signaling modulator 1 deficiency accelerates cystic disease in an orthologous mouse model of ADPKD. Proc Natl Acad Sci U S A, 109: 21462-7, 2012.
  55. Rowe I, Chiaravalli M, Mannella V, Ulisse V, Quilici G, Song X, Xu H, Pema M, Mari S, Qian F, Pei Y, Musco G, and Boletta A. Defective Glucose Metabolism in Polycystic Kidney Disease Identifies A Novel Therapeutic Paradigm. Nat Med.19:488-93, 2013.