Standard Grants: Year 1, $60,000 Each
Mayo Clinic College of Medicine in Rochester, MN: Christopher J. Ward, MB, ChB, PhD
Analysis of the interaction of Polycystin-1 positive exosome-like vesicles with primary cilium
Massachusetts General Hospital in Charlstown, MA: Iain A. Drummond, PhD
Polycystin regulation of ER/Golgi calcium and its role in matrix assembly and secretion
Mayo Clinic College of Medicine in Rochester, MN: Vicente E. Torres, MD, PhD
Role of secretion in polycystic kidney disease
Fellowships: Year 1, $45,000 Each
Brandeis University in Waltham, MA: David B. Doroquez, PhD
Role of intercellular trafficking in C.elegans ciliated sensory neurons: a model for transport in ciliated kidney epithelia
PKD Researcher Information at Brandeis University
Young Investigator Career Development Awards: Year 1, $52,000 Each
Mayo Clinic College of Medicine in Rochester, MN: Jinghua Hu, PhD
Exploring the function of the ciliary ATP synthase in polycystin signaling
Standard Grants: Year 2, $60,000 Each
Oregon Health and Science University in Portland, OR: Sharon Anderson, MD
Estrogen metabolites and experimental polycystic kidney disease
The female hormone estrogen is protective in animal models of PKD, resulting in a less aggressive form of the disease. This study will evaluate the mechanisms by which an estrogen metabolite, 2-hydroxyestradiol, given to male rats slows PKD disease progression.
Brigham and Women's Hospital in Boston, MA: David R. Beier, MD, PhD
Characterization of the role of the Nek8 kinase in development
The mutated Nek8 gene causes a model of ARPKD in jck mice. This project will study the abnormality caused by Nek8 mutation and the proteins and cell signaling pathways involved.
Harvard Medical School in Boston, MA: Thomas L. Benjamin, PhD
TAZ as a possible substrate of Nek kinases
This proposal will characterize a biochemical pathway that regulates the levels of polycystin-2 by degrading it and the role of the TAZ protein in this process.
University of Technology in Aachen, Germany: Carsten Bergmann, MD, PhD
Characterization of the PKHD1 gene and genotype-phenotype studies in autosomal recessive polycystic kidney disease (ARPKD)
The PKHD1 gene, mutated in ARPKD, has a large, complex structure. This proposal will examine the clinical variability in ARPKD in hopes of identifying pathways that will give insight into disease pathogenesis.
Fondazione-Telethon Institute of Genetics and Medicine in Naples, Italy: Brunella Franco, MD
Elucidation of the role of OFD1 in renal cystic disease
This study will investigate the function of the genes mutated Oral-Facial-Digital Syndrome, with the development of kidney cysts, also part of this syndrome.
Indiana University in Indianapolis, IN: Brenda Grimes, PhD
Delivery of a human artificial chromosome harboring a PKD1 transgene into renal epithelial cells
This study proposes to develop an artificial chromosome to deliver normal copies of the PKD1 gene into renal cyst cells grown in culture to determine if the normal gene delivered in this fashion can correct the defect.
Beth Israel Deaconess Medical Center in Boston, MA: Raghu Kalluri, PhD
Stem cell therapy for polycystic kidney disease
This proposal will test whether or not mouse stem cells and human embryonic stem cells can prevent PKD and potentially regress the disease. Initial studies have shown some benefit of stem cells in repairing polycystic kidneys in cystic animal models.
Medical College of Wisconsin in Milwaukee, WI: Xiaogang Li, PhD
Histone deacetylases (HDACs) and Autosomal Dominant Polycystic Kidney Disease (ADPKD)
This study will investigate the functional role of compounds called histone deacetylators (HDACs) that are increased in PKD in cell cycle regulation and ciliary assembly in mouse embryonic kidney cells.
University of Michigan in Ann Arbor, MI: Benjamin Margolis, MD
Regulation of ciliary trafficking by RP2
The protein RP2 has been shown to affect cilia function in retinitis pigmentosa. This study investigates how RPS is involved with the polycystin proteins in the renal cell cilia.
Centre National de la Recherche Scientifique (C.N.R.S.) in Roscoff, France: Laurent Meijer, PhD
Roscovitine-derived pharmacological inhibitors of cyclin-dependent kinases: optimization and characterization for PKD therapeutic application
Roscovitine was found to produce long-lasting arrest of PKD in cystic mouse models. This project will improve the pharmacological properties of roscovitine and its analogs and analyze their cellular and molecular mechanisms of action.
Leiden University Medical Center in Leiden, The Netherlands: Dorien J. Peters, PhD
The role of TGFB-signaling in the progression of polycystic kidney disease
This study proposes to look at the TGFß signaling pathway and its role in the fibrosis that contributes to the impairment of renal function in PKD. The effects of inhibitors of this pathway will be evaluated.
Texas A&M in University College Station, TX: Hongmin Qin, PhD
Identification of effectors for the IFT27, an intraflagellar transport (IFT) particle protein functioning in the cell cycle
IFT proteins are in the cilia and IFT27 is necessary for cell growth. This proposal will try to elucidate the role of IFT27 in the cell cycle and its relationship to the development of PKD.
The Mount Sinai School of Medicine in New York, NY: Rajeev Rohatgi, MD
Biomechanical transduction of gene transcription in renal tubular epithelia
The glycolcalyx is a highly specialized protein and carbohydrate meshwork on the surface of renal tubules and blood vessels and acts as a flow sensor in the latter. This study investigates whether it acts as a flow sensor in renal tubular cells as the cilium has been show to do.
Yale University in New Haven, CT: Mario Strassabosco, MD, PhD
Angiogenesis and progression of liver cysts in ADPKD
The PI proposes to treat ADPKD animal models with compounds that inhibit blood vessel growth and evaluate their effectiveness in slowing the development of liver and kidney cysts.
University of Iowa in Iowa City, IA: Charles Yeaman, PhD
Molecular mechanism of renal deciliation and cystogenesis
Primary cilia extending from renal cells are thought to function as sensors and to maintain normal cell function. This study will test whether or not abnormal loss of cilia resulting from mutation in the PC1 and PC2 genes lead to cyst formation.
Fellowships: Year 2, $45,000 Each
University of Massachusetts Medical School in Worchester, MA: Benedicte Delaval, PhD
Primary role for the centrosome in cilia formation and ciliopathies
The centrosome is a cell organelle involved in cell proliferation and cilia assembly. This study will analyze the proteins associated with the centrosome expressed in Zebrafish embyos in cilia formation and PKD.
Johns Hopkins University School of Medicine in Baltimore, MD: Luis Menezes, MD, PhD
Using induced PKD1 inactivation and network modeling strategies to identify gene networks responsible for post-natal kidney maturation and cystogenesis
Between 12 and 14 days after birth, many genes change their expression pattern in mouse kidney. This proposal will closely examine the changes that characterize this period, which and how genes expressed during this time are affect by mutations in the Pkd1 gene.
University of Kansas Medical Center, The Kidney Institute in Kansas City, KS: Cibele Pinto, PhD
Role of 14-3-3 and A-kinase anchoring proteins on the cAMP-dependent B-Raf signaling and proliferation of ADPKD cells
The aim of this study is to elucidate the mechanism of aberrant cell proliferation that occurs in ADPKD cells and the role of regulatory proteins such as14-3-3 and AKAPs in the process.
Children's Hospital of Boston in Boston, MA: Shan Qin, MD, PhD
Regulation of pkd2 expression by a3ß1 integrin
This project looks at the role of a protein called a3 integrin in cyst formation in PKD and whether its interaction with the extra-cellular matrix has a role in regulating the pkd2 gene.
Cincinnati Children's Hospital Medical Center in Cincinnati, OH: Brian Siroky, PhD
The role of primary cilia in regulating mammalian target of rapamycin signaling
The drug rapamycin affects the mTOR pathway which is thought to contribute to the formation of kidney cysts. This study will determine the role of cilia in the regulation of the mTOR pathway and whether deletion of the PC1 and PC2 proteins affects its activity.
Brigham and Women's Hospital in Boston, MA: Xuefeng Su, PhD
Molecular mechanism of renal cystogenesis in ADPKD
This investigator has identified abnormal activity in an important signaling pathway called Rb/ExR in mouse and human PKD kidney cells. This proposal will determine how the aberrant activity of this pathway may lead to PKD.
Young Investigator Career Development Awards: Year 2, $52,000 Each
The Johns Hopkins University School of Medicine in Baltimore, MD: Michael Kottgen, MD, PhD
Polycystin signaling in Drosophila melanogaster
Polycystin 1 & 2, the protein products of the pdk1 and pkd2 genes, are part of a common signaling pathway in renal cells. This study will examine the specific molecular cues that activate the various processes and try to identify compounds that tell the kidney to form a tubule, not a cyst.
The Penn State University in University Park, PA: Aimin Liu, PhD
The roles for Inturned in kidney development and PKD pathogenesis
This study will investigate in renal tubules a protein Intu that is involved in cilia formation and the regulation of cell polarity in other systems.
Brigham and Women's Hospital in Boston, MA: Shixuan Wang, MD, PhD
Molecular mechanisms of the autosomal recessive polycystic kidney disease
ARPKD is caused by mutations in the PKHD1 gene which makes a protein called polyductin. This study will examine the functions of polyductin in cell replication and its interaction with nuclear proteins.
Translational Grants: Year 2, $80,000 Each
Yale University in New Haven, CT: Joel Rosenbaum, PhD
Discovery of New Polycystic Kidney Disease Drugs Using a Novel, Validated Bioassay in High Throughput Screens
This study will test thousands of potential therapies to slow/stop disease progression in PKD in a surrogate organ system of photosynthetic algae that have polycystin molecules on their flagella. Successful compounds will be validated for efficacy in mammalian cells.
University Hospital Zurich in Zurich, Switzerland: Andreas Serra, MD
Clinical Proof-of-Concept Trial to Assess the Therapeutic Effect of Sirolimus in Patients with Autosomal Dominant Polycystic Kidney Disease: SUISSE ADPKD Study [NCT00346918]
This is a small pilot study to test the efficacy of the drug sirolimus on 100 ADPKD patients with normal or near-normal kidney function to slow or stop disease progression.
Core Grants: Year 2
Indiana University in Indianapolis, IN: Vicente H. Gattone, II, PhD
Electron microscopy core facility for PKD researchers
Mayo Clinic College of Medicine in Rochester, MN: Peter C. Harris, PhD
ADPKD gene mutation registry