Abstract

AutosomalDominantPolycystickidneydisease(ADPKD)ischaracterizedbynumerouscysts withinthekidneysofafflictedindividuals.ThecystsformedinADPKDcangreatlyenlargethe kidneyswhilereplacingthenormalkidneystructures,resultinginreducedkidneyfunctionand progressiontoend-stagerenaldisease,thatcanonlybetreatedbylifelongdialysisorkidney transplants.Asadiseasethataffects1in800~1000individuals,ADPKDisamongthemost commongeneticdisorders.IntheUnitedStates,thereare600,000individuals,andworldwide 12.5million,withPKD[1].Thus,ADPKDrepresentsamajorpublichealthissue,and accountsforhundredsofmillions(andperhapsoverabillion)ofdollarsinhealthcarecosts, particularlyfordialysistreatmentsandthecostofdrugsthatpreventtransplantrejections,as wellasthecostinvolvedofdecreasedproductivityandimpairedqualityoflifeofindividuals withADPKD.Forallthesereasons,itisofgreatimportancetodiscovertreatmentsthat directlyaffectthemolecularcausesofADPKD,andthatwillpreventtheprogressiontoend- stagerenaldiseaseanddialysisortransplantation. Overthepast5yearstheKreidberglaboratoryhasinvestigatedtheroleofWntsignalingin thepathogenesisofADPKD.Dr.Kreidberg?slaboratoryhasfoundthatWntsignalingand?- cateninexpressionishighlyelevatedincystliningcellsinADPKD.Inthisgranttheypropose toextendtheirstudiestounderstandhowaputative?-catenintargetgene,fibronectin,affects cystformation.Fibronectinisakeyextracellularmatrixgeneprimarilyfoundina mesenchymalmatrix,butover-expressedincystickidneys.Wewillstudytheroleof integrin:fibronectininteractionsinADPKD.

Public Health Relevance

AutosomalDominantPolycystickidneydisease(ADPKD)isahereditarydiseasewitha highprevalenceandwithoutacure.ADPKDischaracterizedbynumerouscystswithin thekidneysofafflictedindividuals.OurstudiesonPKDhavefocusedonhow biochemicalsignalingisabnormalincellscarryingmutationsthatcausePKD,andhow theseabnormalsignalsresultintheinitiationofcysts.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK123364-02
Application #
10021645
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Maric-Bilkan, Christine
Project Start
2019-09-20
Project End
2022-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Boston Children's Hospital
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115