Whitney Besse, MD
Assistant Professor of Medicine (Nephrology)Cards
Appointments
Contact Info
Yale School of Medicine
Dept. of Internal Medicine, Section of Nephrology, PO Box 208029
New Haven, CT 06520
United States
About
Titles
Assistant Professor of Medicine (Nephrology)
Biography
Dr. Besse received her bachelors degree in Biomedical Engineering from Brown University in 2003, pre-doctoral training in genetics at the Joslin Diabetes Center at the Harvard Medical School, her M.D. from the University of Connecticut School of Medicine in 2009, and clinical training in Internal Medicine/Nephrology at Yale. Dr. Besse joined Yale School of Medicine faculty in the Department of Internal Medicine, Section of Nephrology in 2019. Her research training in Nephrology has been under the mentorship of Dr. Stefan Somlo, C.N.H Long Professor of Medicine (Nephrology) and Professor of Genetics.
Dr. Besse's field of research interest is genetic kidney diseases, with initial focus on polycystic kidney disease. She uses genetic approaches to identify novel disease genes for dominantly inherited polycystic kidney and liver diseases: a phenotypic spectrum from autosomal dominant polycystic kidney disease (ADPKD) to isolated polycystic liver disease (PCLD), and both in vitro and animal models to further disease gene mechanism investigation. Her identification and investigation of multiple genes has contributed understanding to how the central PKD protein, Polycystin-1, matures through the endoplasmic reticulum. She has contributed approaches for gene validation to the field. Dr. Besse has an active research program recruiting patients with genetically unresolved polycystic kidney and/or liver disease or other inherited kidney diseases for projects involving gene/pathway discovery and variant analysis in genetic kidney diseases. The goal of her lab is to have the identification of novel disease genes serve as an entry point for molecular biology investigation that contributes to a better understanding of disease mechanism and the identification of successful targets for treatments.
Appointments
Nephrology
Assistant ProfessorPrimary
Other Departments & Organizations
- Internal Medicine
- Janeway Society
- Nephrology
- Polycystic Kidney Disease Program
- Yale Center for Genomic Health
- Yale Medicine
Education & Training
- Postdoctoral Research Fellow
- Yale School of Medicine (2018)
- Clinical Fellow, Research Track
- Yale School of Medicine (2015)
- Resident
- Yale School of Medicine (2012)
- MD
- University of Connecticut School of Medicine (2009)
- BS (Hon)
- Brown University, Biomedical Engineering (2003)
Research
Overview
Medical Subject Headings (MeSH)
ORCID
0000-0002-8283-1507
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Stefan Somlo, MD
Neera Dahl, MD, PhD
Dhanpat Jain, MD
Elena Wilson
Haris Mirza, MBBS, PhD
Sherry Mansour, MD, MS
Polycystic Kidney, Autosomal Dominant
Kidney Diseases
Exome Sequencing
Polycystic Kidney Diseases
Publications
Featured Publications
Dnajb11-Kidney Disease Develops from Reduced Polycystin-1 Dosage but not Unfolded Protein Response in Mice
Roy S, Li Z, Guo Z, Long K, Rehrl S, Tian X, Dong K, Besse W. Dnajb11-Kidney Disease Develops from Reduced Polycystin-1 Dosage but not Unfolded Protein Response in Mice. Journal Of The American Society Of Nephrology 2023, 34: 1521-1534. PMID: 37332102, PMCID: PMC10482070, DOI: 10.1681/asn.0000000000000164.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsUnfolded protein responseAutosomal dominant tubulointerstitial kidney diseaseAutosomal dominant polycystic kidney diseasePolycystin-1Autosomal-dominant polycystic kidney diseaseProtein responseTubulointerstitial kidney diseaseKidney diseaseRenal failureRenal failure in adulthoodPolycystic kidney diseaseUnfolded protein response activationFull-length proteinProteins polycystin-1C-terminal fragmentCystic kidneysSite of maturationCystic kidney dysplasiaKidney disease pathogenesisHeterozygous inactivating mutationsHsp40 cochaperonesEndoplasmic reticulumMouse model studiesConditional allelesDNAJB11ALG9 Mutation Carriers Develop Kidney and Liver Cysts
Besse 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.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsProteins polycystin-1Autosomal dominant polycystic kidney diseaseDisease genesRare loss-of-function variantsN-glycan precursorsNovel disease genesLoss-of-function variantsEndoplasmic reticulum lumenLoss-of-function mutationsMonogenic kidney diseaseWhole-exome sequencingGenotype-phenotype correlationProtein biogenesisProtein maturationReticulum lumenPolycystin-1Endoplasmic reticulumGene productsPopulation-based cohortCell-based assaysPhenotypic characterizationPolycystic phenotypeMutation carrier stateDefective glycosylationDominant polycystic kidney diseaseIsolated polycystic liver disease genes define effectors of polycystin-1 function
Besse 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.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAdultAnimalsCalcium-Binding ProteinsCell Line, TransformedCystsEndoplasmic ReticulumFemaleGenome-Wide Association StudyGlucosidasesGlucosyltransferasesHeterozygoteHumansIntracellular Signaling Peptides and ProteinsLiver DiseasesMaleMembrane ProteinsMiceMolecular ChaperonesMutationRNA-Binding ProteinsSEC Translocation ChannelsTRPP Cation ChannelsConceptsPolycystin-1 functionPolycystin-1Protein biogenesis pathwaysGenome-wide basisPolycystic liver diseaseLoss-of-function mutationsWhole-exome sequencingHeterozygous loss-of-function mutationsBiogenesis pathwayLoss of functionAdditional genesDisease genesGene productsCell line modelsCandidate genesExome sequencingEndoplasmic reticulumCausative genesFunction mutationsGenesAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseaseSec63Defective maturationKidney cystsAdult 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.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAutosomal recessive polycystic kidney diseaseSomatic second-hit mutationsAutosomal dominant polycystic kidney diseaseSecond-hit mutationsPolycystic liver diseaseLiver phenotypePolycystic kidney diseaseBile duct homeostasisSecond hit mutationLiver cystsLiver diseaseKidney diseaseCyst formationGenetic interactionsPattern of inheritanceDisease genesRecessive polycystic kidney diseaseGermline inheritanceDominant polycystic kidney diseaseDuctal plate formationWeeks of ageRecessive genotypeSubset of adultsSomatic mutationsPlate formatMonoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease
Gall 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.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsWhole-exome sequencingEnd-stage renal diseaseAutosomal dominant polycystic kidney diseasePhenotypically similar familiesNext-generation sequencingDevelopment of kidney cystsCystic kidneysPolycystic kidney diseaseTargeted next-generation sequencingFrameshift changesInterstitial fibrosisKidney diseasePhenotypic hybridsMissense variantsMembrane proteinsTrafficking defectsADTKDEpisodes of goutLate-onset end-stage renal diseaseProgressive interstitial fibrosisAffected membersMultigenerational familiesCo-factorPhenotypic overlapPartial phenotypic overlapA noncoding variant in GANAB explains isolated polycystic liver disease (PCLD) in a large family
Besse 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.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsLoss-of-function variantsSequence analysis pipelineWhole-exome sequencing analysisExome sequencing dataExome sequencing analysisBase pair deletionSkipping of exonIsolated polycystic liver diseaseNoncoding variantsLinkage analysisDisease genesSequence dataGene discoveryMinigene assayLinkage disequilibriumCoding regionSNP genotypingSequence analysisGenomic evaluationPolycystic liver diseaseSplice donorIdentified mutationsMutation detectionPair deletionGANABGenetic Analysis of Severe Polycystic Liver Disease in Japan
Mizuno H, Besse W, Sekine A, Long K, Kurihara S, Oba Y, Yamanouchi M, Hasegawa E, Suwabe T, Sawa N, Ubara Y, Somlo S, Hoshino J. Genetic Analysis of Severe Polycystic Liver Disease in Japan. Kidney360 2024, 5: 1106-1115. PMID: 38689396, PMCID: PMC11371350, DOI: 10.34067/kid.0000000000000461.Peer-Reviewed Original ResearchConceptsSevere polycystic liver diseaseAutosomal dominant polycystic kidney diseaseDisease genesPolycystic liver diseasePKD2 patientsGenetic analysisWhole-exome sequencingSuspected pathogenic variantsLiver diseaseSpectrum of phenotypesPKD2 variantsExome sequencingAutosomal dominant polycystic kidney disease cohortPathogenic variantsPKD2PKD1Genetic etiologyDominant polycystic kidney diseaseGenesPolycystic kidney diseaseKidney cystsNo significant differenceKidney volumePLD patientsKidney disease
2024
Advancing Genetic Testing in Kidney Diseases: Report From a National Kidney Foundation Working Group
Franceschini N, Feldman D, Berg J, Besse W, Chang A, Dahl N, Gbadegesin R, Pollak M, Rasouly H, Smith R, Winkler C, Gharavi A, Group N, Ars E, Bekheirnia M, Bier L, Bleyer A, Fuller L, Halbritter J, Harris P, Kiryluk K, Knoers N, Kopp J, Kramer H, Lagas S, Lieske J, Lu W, Mannon R, Markowitz G, Moe O, Nadkarni G, Nast C, Parekh R, Pei Y, Reed K, Rehm H, Richards D, Roberts M, Sabatello M, Salant D, Sampson M, Sanna-Cherchi S, Santoriello D, Sedor J, Sneddon T, Watnick T, Wilfond B, Williams W, Wong C. Advancing Genetic Testing in Kidney Diseases: Report From a National Kidney Foundation Working Group. American Journal Of Kidney Diseases 2024 PMID: 39033956, DOI: 10.1053/j.ajkd.2024.05.010.Peer-Reviewed Original ResearchAltmetricConceptsGenetic testingAllied health professionalsImplementation of genetic testingModified Delphi processChronic kidney diseaseScreening of kidney diseasesHealth professionalsWorking GroupKidney diseaseGenetic risk factorsDelphi processWorking group of expertsNational Kidney FoundationPolygenic causeDisease of multiple causesClinical decisionsRisk factorsGroup of expertsCause of kidney diseaseKidney FoundationGenetic basisMultiple causesGroup consensusGenetic causeMonogenic disorders
2023
Sex, Genotype, and Liver Volume Progression as Risk of Hospitalization Determinants in Autosomal Dominant Polycystic Liver Disease
Schönauer R, Sierks D, Boerrigter M, Jawaid T, Caroff L, Audrezet M, Friedrich A, Shaw M, Degenhardt J, Forberger M, de Fallois J, Bläker H, Bergmann C, Gödiker J, Schindler P, Schlevogt B, Müller R, Berg T, Patterson I, Griffiths W, Sayer J, Consortium G, Ambrose J, Arumugam P, Bevers R, Bleda M, Boardman-Pretty F, Boustred C, Brittain H, Caulfield M, Chan G, Elgar G, Fowler T, Giess A, Hamblin A, Henderson S, Hubbard T, Jackson R, Jones L, Kasperaviciute D, Kayikci M, Kousathanas A, Lahnstein L, Leigh S, Leong I, Lopez J, Maleady-Crowe F, McEntagart M, Minneci F, Moutsianas L, Mueller M, Murugaesu N, Need A, O’Donovan P, Odhams C, Patch C, Pereira M, Perez-Gil D, Pullinger J, Rahim T, Rendon A, Rogers T, Savage K, Sawant K, Scott R, Siddiq A, Sieghart A, Smith S, Sosinsky A, Stuckey A, Tanguy M, Tavares A, Thomas E, Thompson S, Tucci A, Welland M, Williams E, Witkowska K, Wood S, Popp B, Torres V, Hogan M, Somlo S, Watnick T, Nevens F, Besse W, Gall E, Harris P, Drenth J, Halbritter J. Sex, Genotype, and Liver Volume Progression as Risk of Hospitalization Determinants in Autosomal Dominant Polycystic Liver Disease. Gastroenterology 2023, 166: 902-914. PMID: 38101549, DOI: 10.1053/j.gastro.2023.12.007.Peer-Reviewed Original ResearchCitationsAltmetricConceptsAutosomal dominant polycystic liver diseasePolycystic liver diseaseDisease-related hospitalizationsLiver diseaseLiver eventsPathogenic variantsPrimary clinical end pointCombination of female sexCohort of patientsClinical end pointsInternational multicenter cohortPrediction of disease progressionGenotype-phenotype correlationPrimary clinical endpointTotal liver volumeUnderlying genetic defectSymptomatic hepatomegalyDesign of randomized controlled trialsRandomized controlled trialsFemale patientsIndependent of sexMulticenter cohortFemale preponderanceRare conditionSymptomatic diseaseCombined Consideration of Sex, Genotype, and Total Liver Volume Progression Determines the Risk of Hospitalization in an International Multicenter Cohort of Autosomal Dominant Polycystic Liver Disease
Sierks D, Schönauer R, Boerrigter M, Jawaid T, Audrezet M, Caroff L, Degenhardt J, de Fallois J, Schlevogt B, Berg T, Nevens F, Watnick T, Sayer J, Besse W, Gall E, Harris P, Drenth J, Halbritter J. Combined Consideration of Sex, Genotype, and Total Liver Volume Progression Determines the Risk of Hospitalization in an International Multicenter Cohort of Autosomal Dominant Polycystic Liver Disease. Journal Of The American Society Of Nephrology 2023, 34: 934-935. DOI: 10.1681/asn.20233411s1934c.Peer-Reviewed Original Research
Clinical Trials
Current Trials
Genetic Determinants of Aneurysms in Autosomal Dominant Polycystic Kidney Disease
HIC ID2000029350RoleSub InvestigatorPrimary Completion Date12/31/2022Recruiting ParticipantsGenderBothAge18+ yearsGenetic Studies of Polycystic Livers
HIC ID0003010983RolePrincipal InvestigatorPrimary Completion Date04/01/2024Recruiting ParticipantsGenderBothAge18+ years
Academic Achievements & Community Involvement
activity Yale Physician Associate Program
Peer Review Groups and Grant Study SectionsReviewerDetailsClass of 2024 PA Thesis Readers Committee2024 - Presenthonor Young Physician-Scientist Award
National AwardAmerican Society for Clinical InvestigationDetails03/31/2022United Stateshonor Clinical Scientist Development Award
National AwardDoris Duke Charitable FoundationDetails07/01/2021United Stateshonor Mentored Research Award
Regional AwardRobert E. Leet and Clara Guthrie Patterson TrustDetails02/01/2019United Stateshonor Polycystic Kidney Disease Research Award
National AwardPolycystic Kidney Disease FoundationDetails07/01/2018United States
Clinical Care
Overview
Clinical Specialties
Fact Sheets
Polycystic Kidney Disease (PKD)
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News
- February 23, 2024
Department of Internal Medicine Promotions and Appointments (February 2024)
- October 24, 2023
Yale Contributions Shape ASN Kidney Week 2023
- February 13, 2023
Khera Receives ASCI Young Physician-Scientist Award
- July 27, 2022
Yale SUMR Program Hosts Undergraduates Interested in Research
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Contacts
Yale School of Medicine
Dept. of Internal Medicine, Section of Nephrology, PO Box 208029
New Haven, CT 06520
United States
Administrative Support
Events
Organization Only Justin Belcher, MD, PhD, FASN
Organization Only Cancelled
Organization Only Dennis G Moledina, MD, PhD, FASN
Organization Only