Richard Lifton, MD, PhD
Professor (Adjunct) of GeneticsCards
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Professor (Adjunct) of Genetics
Biography
Richard Lifton is Professor, Adjunct of Genetics. Lifton was the Chair of the Department of Genetics from 1998-2016, Sterling Professor of Genetics and Internal Medicine, Founder and Executive Director of the Yale Center for Genome Analysis and Investigator of the Howard Hughes Medical Institute at Yale School of Medicine.He graduated summa cum laude from Dartmouth College, then received MD and PhD degrees (in Biochemistry) from Stanford University. Following clinical training in Internal Medicine at Brigham and Women’s Hospital, he continued on the faculty at Harvard Medical School before being recruited to Yale in 1993.
Lifton has used human genetics and genomics to identify rare mutations with large effect and elucidate biochemical mechanisms underlying diverse common diseases.In the particular case of hypertension, which affects more than a billion people worldwide and is a principal risk factor for heart attack, stroke and heart failure, together the leading cause of death worldwide, Lifton’s work has identified mutations and biochemical mechanisms that drive blood pressure to the highest and lowest blood pressures compatible with survival, implicating altered renal salt reabsorption in blood pressure variation. This work has also identified a previously unrecognized pathway that orchestrates the balance between salt and potassium homeostasis, providing a mechanism for dietary potassium’s ability to lower blood pressure. These findings provided the scientific basis for reducing salt balance in the prevention and treatment of hypertension, strategies that are used worldwide. Finding mutations underlying extreme outliers of common disease to identify pathways that can manipulated for health benefit has been broadly applied.
In 2009 Lifton’s group developed exome sequencing, selectively sequencing all of the genes in the human genome at very low cost, and demonstrated the utility of the technology by performing the first clinical diagnosis by genome-level sequencing. This technology has been widely used for discovery of hundreds of disease and trait loci. Lifton’s group has used this technology to discover genes underlying diverse cardiovascular, renal, and neoplastic diseases. These include discovery of mutations in chromatin modifiers that underlie congenital heart disease, and discovery that hormone-producing tumors are commonly caused by single somatic mutations.
Lifton is an elected member of the National Academy of Sciences, the National Academy of Medicine and the American Academy of Arts and Sciences.He has served on the Governing Councils of the National Academy of Sciences, the National Academy of Medicine, the Advisory Council to the NIH Director, the Scientific Advisory Boards of the Whitehead Institute of MIT, the Broad Institute of MIT and Harvard, the Simons Foundation for Autism Research and the Massachusetts General Hospital. He has also served as Co-Chair of the Planning Committee for the President’s Precision Medicine Initiative.
Lifton has received the highest scientific awards of the American Heart Association, the American Society of Nephrology, the Council for High Blood Pressure Research, the American Society of Hypertension, the International Society of Hypertension, and the International Society of Nephrology.He received the 2008 Wiley Prize for Biomedical Sciences and the 2014 Breakthrough Prize in Life Sciences.
Appointments
Genetics
Professor AdjunctPrimary
Other Departments & Organizations
- Dean's Workshops
- Fellowship Training
- Genetics
- High Performance Computation
- Proteomics
- Yale Cancer Center
- Yale Ventures
Education & Training
- PhD
- Stanford University (1986)
- MD
- Stanford University (1982)
- BA
- Dartmouth College (1975)
Research
Overview
By investigation of rare families recruited from around the world with extreme phenotypes suggesting genetic causation, we have identified genes that cause to these traits, putting a molecular face on their pathogenesis. In 2009 we reduced to practice the rapid and inexpensive sequencing of all genes in the genome and have used this platform for discovery of rare mutations with large effect in cardiovascular disease, cancer, kidney disease, skin disease and immunologic disease. These studies have revealed new pathways and mechanisms that regulate metabolic traits including blood pressure, bone mass, and electrolyte homeostasis, and genes that when mutated cause diverse diseases including heart attacks, strokes, kidney disease, cancer, autoinflammatory disease, skin disease and congenital heart disease. These studies have defined new strategies for disease gene discovery and point to the opportunity to determine the consequence of mutation of every gene in the human genome.
Medical Research Interests
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Kaya Bilguvar, MD, PhD
Kristopher Kahle, MD, PhD
Francesc Lopez-Giraldez, PhD
Gilbert Moeckel, MD, PhD, FASN
Jean-Ju Chung, PhD, MS
Jesse Rinehart, PhD
Mutation
Lymphoma, T-Cell, Cutaneous
Hyperaldosteronism
Publications
2024
AXIN1 mutations in nonsyndromic craniosynostosis.
Timberlake A, Hemal K, Gustafson J, Hao L, Valenzuela I, Slavotinek A, Cunningham M, Kahle K, Lifton R, Persing J. AXIN1 mutations in nonsyndromic craniosynostosis. Journal Of Neurosurgery Pediatrics 2024, 34: 246-251. PMID: 38905707, PMCID: PMC11200303, DOI: 10.3171/2024.5.peds24115.Peer-Reviewed Original ResearchAltmetricConceptsSequence dataAXIN1 mutationsCase-parent triosGenome-wide significanceCS casesNonsyndromic CSGenome sequencing projectsWnt signalingExome sequencing dataRNA sequencing dataPhenotypes associated with mutationsSequencing projectsGenetic testingInhibitor of Wnt signalingLive birthsNonsyndromic casesGenetic etiologyGenetic causeCS patientsAXIN1Nonsyndromic craniosynostosisMutationsHealthy controlsBirth defectsExome184 PTEN Mutations Portend Cerebral Ventriculomegaly With Autism-Like Deficits in Cortical Circuitry
DeSpenza T, Kizlitug E, Allington G, Barson D, O'Connor D, Robert S, Mekbib K, Singh A, Phan D, Nanda P, Mandino F, Constable T, Lake E, Carter B, Gunel M, Lifton R, Luikart B, Kahle K. 184 PTEN Mutations Portend Cerebral Ventriculomegaly With Autism-Like Deficits in Cortical Circuitry. Neurosurgery 2024, 70: 46-46. DOI: 10.1227/neu.0000000000002809_184.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingFetal ventriculomegalyCongenital hydrocephalusExome sequencingChoroid plexus hyperplasiaMutated genesCa2+ imagingMutant mouse modelsPTEN mutantsHuman fetal brainPten mutant miceSporadic CHCerebral ventriculomegalyCSF diversionObstructive hydrocephalusCH patientsCSF secretionPharmacological mTORC1 inhibitionNeurodevelopmental assessmentRadiographic biomarkersFetal brainPTEN mutationsAqueductal stenosisPTEN deletionVentriculomegalyReply to Pisan et al.: Pathogenicity of inherited TRAF7 mutations in congenital heart disease
Mishra-Gorur K, Barak T, Kaulen L, Henegariu O, Jin S, Aguilera S, Yalbir E, Goles G, Nishimura S, Miyagishima D, Djenoune L, Altinok S, K. D, Viviano S, Prendergast A, Zerillo C, Ozcan K, Baran B, Sencar L, Goc N, Yarman Y, Ercan-encicek A, Bilguvar K, Lifton R, Moliterno J, Louvi A, Yuan S, Deniz E, Brueckner M, Gunel M. Reply to Pisan et al.: Pathogenicity of inherited TRAF7 mutations in congenital heart disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319578121. PMID: 38466853, PMCID: PMC10963000, DOI: 10.1073/pnas.2319578121.Commentaries, Editorials and LettersAuthor Correction: GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway
Park A, Leney-Greene M, Lynberg M, Gabrielski J, Xu X, Schwarz B, Zheng L, Balasubramaniyam A, Ham H, Chao B, Zhang Y, Matthews H, Cui J, Yao Y, Kubo S, Chanchu J, Morawski A, Cook S, Jiang P, Ravell J, Cheng Y, George A, Faruqi A, Pagalilauan A, Bergerson J, Ganesan S, Chauvin S, Aluri J, Edwards-Hicks J, Bohrnsen E, Tippett C, Omar H, Xu L, Butcher G, Pascall J, Karakoc-Aydiner E, Kiykim A, Maecker H, Tezcan İ, Esenboga S, Heredia R, Akata D, Tekin S, Kara A, Kuloglu Z, Unal E, Kendirli T, Dogu F, Karabiber E, Atkinson T, Cochet C, Filhol O, Bosio C, Davis M, Lifton R, Pearce E, Daumke O, Aytekin C, Şahin G, Aksu A, Uzel G, Koneti Rao V, Sari S, Dalgıç B, Boztug K, Cagdas D, Haskologlu S, Ikinciogullari A, Schwefel D, Vilarinho S, Baris S, Ozen A, Su H, Lenardo M. Author Correction: GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway. Nature Immunology 2024, 25: 717-717. PMID: 38347083, DOI: 10.1038/s41590-024-01779-z.Peer-Reviewed Original ResearchAltmetricCorrection: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
Matuozzo D, Talouarn E, Marchal A, Zhang P, Manry J, Seeleuthner Y, Zhang Y, Bolze A, Chaldebas M, Milisavljevic B, Gervais A, Bastard P, Asano T, Bizien L, Barzaghi F, Abolhassani H, Tayoun A, Aiuti A, Darazam I, Allende L, Alonso-Arias R, Arias A, Aytekin G, Bergman P, Bondesan S, Bryceson Y, Bustos I, Cabrera-Marante O, Carcel S, Carrera P, Casari G, Chaïbi K, Colobran R, Condino-Neto A, Covill L, Delmonte O, Zein L, Flores C, Gregersen P, Gut M, Haerynck F, Halwani R, Hancerli S, Hammarström L, Hatipoğlu N, Karbuz A, Keles S, Kyheng C, Leon-Lopez R, Franco J, Mansouri D, Martinez-Picado J, Akcan O, Migeotte I, Morange P, Morelle G, Martin-Nalda A, Novelli G, Novelli A, Ozcelik T, Palabiyik F, Pan-Hammarström Q, de Diego R, Planas-Serra L, Pleguezuelo D, Prando C, Pujol A, Reyes L, Rivière J, Rodriguez-Gallego C, Rojas J, Rovere-Querini P, Schlüter A, Shahrooei M, Sobh A, Soler-Palacin P, Tandjaoui-Lambiotte Y, Tipu I, Tresoldi C, Troya J, van de Beek D, Zatz M, Zawadzki P, Al-Muhsen S, Alosaimi M, Alsohime F, Baris-Feldman H, Butte M, Constantinescu S, Cooper M, Dalgard C, Fellay J, Heath J, Lau Y, Lifton R, Maniatis T, Mogensen T, von Bernuth H, Lermine A, Vidaud M, Boland A, Deleuze J, Nussbaum R, Kahn-Kirby A, Mentre F, Tubiana S, Gorochov G, Tubach F, Hausfater P, Meyts I, Zhang S, Puel A, Notarangelo L, Boisson-Dupuis S, Su H, Boisson B, Jouanguy E, Casanova J, Zhang Q, Abel L, Cobat A. Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19. Genome Medicine 2024, 16: 6. PMID: 38184654, PMCID: PMC10771638, DOI: 10.1186/s13073-023-01278-0.Peer-Reviewed Original ResearchAltmetricGIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway
Park A, Leney-Greene M, Lynberg M, Gabrielski J, Xu X, Schwarz B, Zheng L, Balasubramaniyam A, Ham H, Chao B, Zhang Y, Matthews H, Cui J, Yao Y, Kubo S, Chanchu J, Morawski A, Cook S, Jiang P, Ravell J, Cheng Y, George A, Faruqi A, Pagalilauan A, Bergerson J, Ganesan S, Chauvin S, Aluri J, Edwards-Hicks J, Bohrnsen E, Tippett C, Omar H, Xu L, Butcher G, Pascall J, Karakoc-Aydiner E, Kiykim A, Maecker H, Tezcan İ, Esenboga S, Heredia R, Akata D, Tekin S, Kara A, Kuloglu Z, Unal E, Kendirli T, Dogu F, Karabiber E, Atkinson T, Cochet C, Filhol O, Bosio C, Davis M, Lifton R, Pearce E, Daumke O, Aytekin C, Şahin G, Aksu A, Uzel G, Koneti Rao V, Sari S, Dalgıç B, Boztug K, Cagdas D, Haskologlu S, Ikinciogullari A, Schwefel D, Vilarinho S, Baris S, Ozen A, Su H, Lenardo M. GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway. Nature Immunology 2024, 25: 282-293. PMID: 38172257, PMCID: PMC11151279, DOI: 10.1038/s41590-023-01691-y.Peer-Reviewed Original ResearchCitationsAltmetric
2023
A novel SMARCC1 BAFopathy implicates neural progenitor epigenetic dysregulation in human hydrocephalus
Singh A, Allington G, Viviano S, McGee S, Kiziltug E, Ma S, Zhao S, Mekbib K, Shohfi J, Duy P, DeSpenza T, Furey C, Reeves B, Smith H, Sousa A, Cherskov A, Allocco A, Nelson-Williams C, Haider S, Rizvi S, Alper S, Sestan N, Shimelis H, Walsh L, Lifton R, Moreno-De-Luca A, Jin S, Kruszka P, Deniz E, Kahle K. A novel SMARCC1 BAFopathy implicates neural progenitor epigenetic dysregulation in human hydrocephalus. Brain 2023, 147: 1553-1570. PMID: 38128548, PMCID: PMC10994532, DOI: 10.1093/brain/awad405.Peer-Reviewed Original ResearchCitationsAltmetricConceptsAqueductal stenosisDe novo variantsCardiac defectsCerebral ventriculomegalyPatient cohortFetal brain transcriptomeStructural brain disordersTranscription factor NeuroD2Large patient cohortCorpus callosum abnormalitiesHuman fetal brainOptical coherence tomographyWhole-exome sequencingNeural stem cellsCH patientsHuman hydrocephalusControl cohortClinical managementCommon disorderCallosum abnormalitiesFetal brainBrain disordersBrain surgeryCH pathogenesisPatientsLRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility
Hwang J, Chai P, Nawaz S, Choi J, Lopez-Giraldez F, Hussain S, Bilguvar K, Mane S, Lifton R, Ahmad W, Zhang K, Chung J. LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility. ELife 2023, 12: rp90095. PMID: 38091523, PMCID: PMC10721216, DOI: 10.7554/elife.90095.Peer-Reviewed Original ResearchCitationsAltmetricLRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility
Hwang J, Chai P, Nawaz S, Choi J, Lopez-Giraldez F, Hussain S, Bilguvar K, Mane S, Lifton R, Ahmad W, Zhang K, Chung J. LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility. ELife 2023, 12 DOI: 10.7554/elife.90095.3.Peer-Reviewed Original ResearchCitationsAltmetricInborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
Lee D, Le Pen J, Yatim A, Dong B, Aquino Y, Ogishi M, Pescarmona R, Talouarn E, Rinchai D, Zhang P, Perret M, Liu Z, Jordan I, Bozdemir S, Bayhan G, Beaufils C, Bizien L, Bisiaux A, Lei W, Hasan M, Chen J, Gaughan C, Asthana A, Libri V, Luna J, Jaffré F, Hoffmann H, Michailidis E, Moreews M, Seeleuthner Y, Bilguvar K, Mane S, Flores C, Zhang Y, Arias A, Bailey R, Schlüter A, Milisavljevic B, Bigio B, Le Voyer T, Materna M, Gervais A, Moncada-Velez M, Pala F, Lazarov T, Levy R, Neehus A, Rosain J, Peel J, Chan Y, Morin M, Pino-Ramirez R, Belkaya S, Lorenzo L, Anton J, Delafontaine S, Toubiana J, Bajolle F, Fumadó V, DeDiego M, Fidouh N, Rozenberg F, Pérez-Tur J, Chen S, Evans T, Geissmann F, Lebon P, Weiss S, Bonnet D, Duval X, Pan-Hammarström Q, Planas A, Meyts I, Haerynck F, Pujol A, Sancho-Shimizu V, Dalgard C, Bustamante J, Puel A, Boisson-Dupuis S, Boisson B, Maniatis T, Zhang Q, Bastard P, Notarangelo L, Béziat V, de Diego R, Rodriguez-Gallego C, Su H, Lifton R, Jouanguy E, Cobat A, Alsina L, Keles S, Haddad E, Abel L, Belot A, Quintana-Murci L, Rice C, Silverman R, Zhang S, Casanova J, Alavoine L, Behillil S, Burdet C, Charpentier C, Dechanet A, Descamps D, Duval X, Ecobichon J, Enouf V, Frezouls W, Houhou N, Kafif O, Lehacaut J, Letrou S, Lina B, Lucet J, Manchon P, Nouroudine M, Piquard V, Quintin C, Thy M, Tubiana S, van der Werf S, Vignali V, Visseaux B, Yazdanpanah Y, Chahine A, Waucquier N, Migaud M, Deplanque D, Djossou F, Mergeay-Fabre M, Lucarelli A, Demar M, Bruneau L, Gérardin P, Maillot A, Payet C, Laviolle B, Laine F, Paris C, Desille-Dugast M, Fouchard J, Malvy D, Nguyen D, Pistone T, Perreau P, Gissot V, Le Goas C, Montagne S, Richard L, Chirouze C, Bouiller K, Desmarets M, Meunier A, Lefèvre B, Jeulin H, Legrand K, Lomazzi S, Tardy B, Gagneux-Brunon A, Bertholon F, Botelho-Nevers E, Christelle K, Nicolas L, Roufai L, Amat K, Couffin-Cadiergues S, Espérou H, Hendou S, Abel L, Abolhassani H, Aguilera-Albesa S, Aiuti A, Akcan O, Akcay N, Alkan G, Alkhater S, Allende L, Alper Y, Amenzoui N, Anderson M, Arkin L, Aubart M, Avramenko I, Aydemir Ş, Aydin Z, Aytekin C, Aytekin G, Aytekin S, Bando S, Beland K, Belkaya S, Biggs C, Aburto A, Blanchard-Rohner G, Blázquez-Gamero D, Bloomfield M, Bogunovic D, Bondarenko A, Borghesi A, Bousfiha A, Boyarchuk O, Brodin P, Bryceson Y, Bucciol G, Calcaterra V, Casari G, Cavalcanti A, Celik J, Chrousos G, Colobran R, Condino-Neto A, Conti F, Cooper M, Coskuner T, Cyrus C, D’Auria E, Delafontaine S, Drolet B, Duramaz B, Zein L, Elnagdy M, Emiroglu M, Erdeniz E, Fabi M, Feldman H, Fellay J, Fencl F, Filippatos F, Freiss J, Fremuth J, Gagro A, Garcia-Solis B, Vergine G, González-Montelongo R, Gul Y, Gülhan B, Gultekin S, Gut M, Halwani R, Hammarström L, Hatipoğlu N, Heath J, Henrickson S, Hernandez-Brito E, Hoffman I, Hoste L, Hsieh E, Íñigo-Campos A, Itan Y, Jabandziev P, Kandemir B, Kanık-Yüksek S, Kapakli H, Karbuz A, Kasapcopur O, Kechiche R, Demirkol Y, Kilic O, Hansen S, Klocperk A, Lau Y, Lebl J, Lorenzo-Salazar J, Lucas C, Maglorius M, Marque L, Medina Y, Melián A, Mentis A, Pato M, Michos A, Milner J, Mogensen T, Muñoz-Barrera A, Nepesov S, Neves J, Ng A, Ng L, Novelli A, Novelli G, Oz F, Ocejo-Viñals J, Okada S, Orbak Z, Kilic A, Ouair H, Öz Ş, Özçelik T, Özkan E, Parlakay A, Pato C, Paz-Artal E, Pelham S, Pellier I, Philippot Q, Planas-Serra L, Plassart S, Pokorna P, Polat M, Poli C, Prando C, Renia L, Rivière J, Rodríguez-Palmero A, Roussel L, Rubio-Rodriguez L, Salifu M, Sasek L, Sasia L, Scherbina A, Schmitt E, Sediva A, Sevketoglu E, Slaba K, Slaby O, Sobh A, Solé-Violán J, Soler-Palacin P, De Somer L, Sözeri B, Spaan A, Stepanovskiy Y, Tangye S, Tanir G, Tatsi E, Thorball C, Torun S, Turvey S, Uddin M, Uyar E, Valencia-Ramos J, Van Den Rym A, Vatansev H, de Vera M, Vermeulen F, Vinh D, Volokha A, von Bernuth H, Wouters C, Yahşi A, Yarar V, Yesilbas O, Yıldız M, Zatz M, Zawadzki P, Zuccotti G, Zhang S, Casanova J. Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children. Science 2023, 379: eabo3627. PMID: 36538032, PMCID: PMC10451000, DOI: 10.1126/science.abo3627.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsOAS-RNase LInflammatory syndromeCytokine productionInflammatory cytokinesSARS-CoV-2-related multisystem inflammatory syndromeCytosolic double-stranded RNAMultisystem inflammatory syndromeRig-I deficiencySuppress cytokine productionPrimary myeloid cellsRNase LMonocytic cell lineAutosomal recessive deficiencyMyeloid cellsMononuclear phagocytesUnrelated childrenInborn errorsRecessive deficiencyDeficient cellsProtein deficiencyCOVID-19Cell linesCytokinesSyndromeDouble-stranded RNA
Clinical Trials
Current Trials
Congenital Heart Disease GEnetic NEtwork Study (CHD GENES)
HIC ID1010007481RoleSub InvestigatorPrimary Completion Date08/31/2020Recruiting ParticipantsGenderBoth
Academic Achievements & Community Involvement
honor Breakthrough Prize in Life Sciences
National AwardDetails01/01/2014United Stateshonor Member
National AwardAmerican Academy of Arts and SciencesDetails01/01/2012United Statesactivity YALE-UCL Collaborative
ResearchDetails01/01/2011 - PresentLondon, England, United KingdomAbstract/SynopsisDr. Lifton is on the Joint Strategy Committee for the Yale-UCL Collaborative, an alliance which will provide opportunities for high-level scientific research, clinical and educational collaboration across the institutions involved: Yale University, Yale School of Medicine, Yale-New Haven Hospital and UCL (University College London) and UCL Partners
activity Transatlantic Network on Hypertension-Renal Salt Handling in the Control of Blood Pressure
ResearchDetails09/01/2007 - PresentParis, IDF, FranceAbstract/SynopsisDrs Hebert and Lifton will join leading researchers in Switzerland, France and Mexico in a transatlantic collaboration aimed at pinpointing the kidney’s role in high blood pressure.
honor Doctor of Science (Honorary)
National AwardMt. Sinai School of MedicineDetails01/01/2005United States
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