Haifan Lin, PhD
Eugene Higgins Professor of Cell Biology, and Professor of Genetics, of Obstetrics, Gynecology & Reproductive Sciences, and of DermatologyCards
Appointments
Additional Titles
Director, Yale Stem Cell Center
Contact Info
Appointments
Additional Titles
Director, Yale Stem Cell Center
Contact Info
Appointments
Additional Titles
Director, Yale Stem Cell Center
Contact Info
About
Titles
Eugene Higgins Professor of Cell Biology, and Professor of Genetics, of Obstetrics, Gynecology & Reproductive Sciences, and of Dermatology
Director, Yale Stem Cell Center
Biography
The Eugene Higgins Professor of Cell Biology, Professor of Genetics, of Obstetrics, Gynecology, and Reproductive Sciences, and of Dermatology, Founding Director of Yale Stem Cell Center. Dr. Lin’s work is focused on the self-renewing mechanism of stem cells, using Drosophila germline stem cells, mouse germline stem cells, mouse embryonic stem cells, Hydra, and planarian stem cells as models. He also studies germline development and stem cell-related cancers.
Dr. Lin received his B.S. degree from Fudan University (1982) and his Ph.D. degree from Cornell University (1990). Following his postdoctoral research at the Carnegie Institution of Washington, he joined the faculty of Duke University Medical School in 1994, where he rose to the rank of Full Professor. He founded and directed the Duke Stem Cell Research Program (2005-2006) and moved to Yale in 2006 to establish and direct the Yale Stem Cell Center, building it from just two labs to currently one of the largest stem cell research organizations in the world with 100 member labs. With Yale's support, he was the Founding Dean (Adjunct) of School of Life Science and Technology at ShanghaiTech University (2014-2022), where he established a world-class faculty and educational programs in the School.
Dr. Lin has made key contributions to the demonstration of stem cell asymmetric division and the proof of the stem cell niche theory. He discovered the Argonaute/Piwi gene family and elucidated their essential function in stem cell self-renewal and germline development. He is also a discoverer of a novel class of non-coding small RNAs called PIWI-interacting RNAs (piRNAs), a discovery hailed by the Science Magazine as one of the Ten Scientific Breakthroughs in 2006. More recently, he proposed and demonstrated the crucial roles of the Piwi-piRNA pathway in epigenetic programming of gene expression and in post-transcriptional regulation of mRNAs and lncRNAs.
Dr. Lin has played numerous leadership roles in the scientific community world-wide. He is President (2022-2023) of the International Society for Stem Cell Research (ISSCR); and has served as Director (2009-2019, 2020-), Treasurer (2013-2016), Executive Committee Member, Vice President (2020-2021), and President-Elect (2021-2022) of ISSCR; he was Chair of the Finance Committee (2013-2016); Chair the Publications Committee (2009-2012), and Chair the Annual Meeting Program Committee (2010-2011) of the ISSCR. He led the establishment of ISSCR’s official journal, Stem Cell Reports (2010-2012). Dr. Lin has also served on the Medical Advisory Board of New York Stem Cell Foundation (2009-present), the NIH Director’s Pioneer Award Selection Committee (2009), the NIH study sections (1998-2005, 2007, 2012, 2014, 2019-2020), the Board of Directors of the Society of Chinese Biological Investigators, USA (2002-2008), the Council of the Society of Chinese Bioscientists in America (2008-2011), the Advisory Council of RIKEN Center for Developmental Biology, Japan (2007-2015), the Scientific Advisory Board of the Jane Coffin Childs Memorial Fund for Medical Research (2011-2015), National Key Stem Cell Research Advisory Committee, Chinese Ministry of Science and Technology (2011-2014), the Council of Shantou University (2010-2015), and the Council of Connecticut Academy of Science and Engineering (2013-2016). He was a co-founder and Core Member of the Connecticut State Government Life Sciences Advisory Group (2011-2012) and served on the Advisory Board of Connecticut Innovation Bioscience Fund (2017-2020).
Dr. Lin has been serving on Editorial Boards of Cell Stem Cells (2007-), Cell Research (2010-), Stem Cell Reports (2013-), National Science Review (2013-), and Science China (2013-). His past editorial board services included Stem Cells (2005-2008), Biology of Reproduction (2009-2010), Journal of Cell Biology (2009-2014), Current Opinion in Cell Biology (2009-2014). He was a Featured Editor of Nature Reports Stem Cells (2009).
Dr. Lin received many awards and honors, including the Jane Coffin Childs Fellowship for Medical Research (1990), American Cancer Society Junior Faculty Research Award (1996), the March of Dimes Basil O'Connor Scholar Research Award (1996), the David and Lucile Packard Fellowship for Science and Engineering (1996), the G. Harold and Leila Y. Mathers Award (2007, 2011, 2015), the American Society of Andrology Lecturer Award (2008), the Laura Hartenbaum Breast Cancer Foundation’s Legacy for Hope Award (2009), the Ellison Medical Foundation Senior Scholar Award (2010), the NIH Director’s Pioneer Award (2010), the NIH MERIT Award (2012), the Ray Wu Award (the highest honor by the Chinese Biological Investigators Society; 2013), and the Society for the Study of Reproduction Research Award (2015), and the Chinese Association for Science and Technology, USA, Outstanding Science and Innovation Award (2019). He is a Member of US National Academy of Sciences (2018-), a Member of American academy of Arts and Sciences (2018-), and a Fellow of the American Association for the Advancement of Science (2010-).
Appointments
Cell Biology
ProfessorPrimaryDermatology
ProfessorSecondaryGenetics
ProfessorSecondaryObstetrics, Gynecology & Reproductive Sciences
ProfessorSecondary
Other Departments & Organizations
- Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS)
- Cell Biology
- Cell Biology of RNA
- Cell Biology Research
- Center for RNA Science and Medicine
- Computational Biology and Biomedical Informatics
- Dermatology
- Developmental Cell Biology and Genetics
- Diabetes Research Center
- Directors
- Embryonic Stem Cell Research Oversight
- Genetics
- Genomics, Genetics, and Epigenetics
- Molecular Cell Biology, Genetics and Development
- Obstetrics, Gynecology & Reproductive Sciences
- Program in Neurodevelopment and Regeneration
- Yale Cancer Center
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Stem Cell Center
- Yale Ventures
- Yale WRHR Advisory Committee
Education & Training
- PhD
- Cornell University (1990)
- BS
- Fudan University (1982)
Research
Overview
Medical Research Interests
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Nils Neuenkirchen, PhD
Mei Zhong, PhD
Caihong Qiu, PhD
Karla M Neugebauer, PhD
Matt Simon, PhD
Manoj M Pillai, MBBS
Argonaute Proteins
Stem Cells
Embryonic Stem Cells
RNA Processing, Post-Transcriptional
Publications
2024
Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape
Boddu P, Gupta A, Roy R, De La Peña Avalos B, Olazabal-Herrero A, Neuenkirchen N, Zimmer J, Chandhok N, King D, Nannya Y, Ogawa S, Lin H, Simon M, Dray E, Kupfer G, Verma A, Neugebauer K, Pillai M. Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape. Molecular Cell 2024, 84: 1475-1495.e18. PMID: 38521065, PMCID: PMC11061666, DOI: 10.1016/j.molcel.2024.02.032.Peer-Reviewed Original ResearchCitationsAltmetricConceptsRate of RNA polymerase IIChromatin landscapeElongation defectsElongation rate of RNA polymerase IIImpaired protein-protein interactionsSplicing of pre-messenger RNATranscription elongation defectsRNA polymerase IIProtein-protein interactionsPre-messenger RNACancer-associated mutationsIsogenic cell linesSin3/HDAC complexGene bodiesPolymerase IIChromatin accessibilityH3K4me3 markChromatin changesMutant SF3B1ChromatinMutant mouse modelsEpigenetic disordersEpigenetic factorsHuman diseasesMutant state
2023
Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E
Boddu P, Gupta A, Roy R, De La Pena Avalos B, Herrero A, Zimmer J, Simon M, Chandhok N, King D, Neuenkirchen N, Dray E, Lin H, Kupfer G, Verma A, Neugebauer K, Pillai M. Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E. Blood 2023, 142: 714. DOI: 10.1182/blood-2023-187303.Peer-Reviewed Original ResearchCitationsConceptsSplicing factorsChIP-seqK562 cell lineKey regulatory genesCell linesSingle mutant alleleNon-denaturing gelsAlternative splicingTranscriptional kineticsRegulatory genesSpliceosome assemblySplicing efficiencyMRNA splicingCRISPR/Progenitor populationsNeomorphic functionsMolecular mechanismsMutant allelesIsoform changesGene editingNovel mechanismMutationsSF mutationsRecurrent mutationsAssembly kinetics
2022
Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus
Duy PQ, Weise SC, Marini C, Li XJ, Liang D, Dahl PJ, Ma S, Spajic A, Dong W, Juusola J, Kiziltug E, Kundishora AJ, Koundal S, Pedram MZ, Torres-Fernández LA, Händler K, De Domenico E, Becker M, Ulas T, Juranek SA, Cuevas E, Hao LT, Jux B, Sousa AMM, Liu F, Kim SK, Li M, Yang Y, Takeo Y, Duque A, Nelson-Williams C, Ha Y, Selvaganesan K, Robert SM, Singh AK, Allington G, Furey CG, Timberlake AT, Reeves BC, Smith H, Dunbar A, DeSpenza T, Goto J, Marlier A, Moreno-De-Luca A, Yu X, Butler WE, Carter BS, Lake EMR, Constable RT, Rakic P, Lin H, Deniz E, Benveniste H, Malvankar NS, Estrada-Veras JI, Walsh CA, Alper SL, Schultze JL, Paeschke K, Doetzlhofer A, Wulczyn FG, Jin SC, Lifton RP, Sestan N, Kolanus W, Kahle KT. Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus. Nature Neuroscience 2022, 25: 458-473. PMID: 35379995, PMCID: PMC9664907, DOI: 10.1038/s41593-022-01043-3.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCongenital hydrocephalusCerebral ventricular dilatationPrimary defectNeuroepithelial cell differentiationRisk genesCerebrospinal fluid homeostasisWhole-exome sequencingNeuroepithelial stem cellsCortical hypoplasiaReduced neurogenesisVentricular dilatationVentricular enlargementCH mutationsPrenatal hydrocephalusDisease heterogeneityBrain surgeryCSF circulationHydrocephalusGenetic subtypesFluid homeostasisNeuroepithelial cellsNovo mutationsBrain transcriptomicsStem cellsCell differentiationPUMILIO proteins promote colorectal cancer growth via suppressing p21
Gong Y, Liu Z, Yuan Y, Yang Z, Zhang J, Lu Q, Wang W, Fang C, Lin H, Liu S. PUMILIO proteins promote colorectal cancer growth via suppressing p21. Nature Communications 2022, 13: 1627. PMID: 35338151, PMCID: PMC8956581, DOI: 10.1038/s41467-022-29309-1.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsColorectal cancerAOM/DSS modelIntestine-specific knockoutColitis-associated cancerHuman CRC cellsOrthotopic colon cancer modelColorectal cancer growthG1/S transitionHuman colorectal cancerColorectal tumor growthColon cancer modelCancer cell growthCRC progressionCRC cellsIntravenous injectionTherapeutic targetCancer growthCancer modelTumor growthSignificant decreaseS transitionDirect targetP21 mRNACancerDSS modelPrecision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies
Biancon G, Joshi P, Zimmer JT, Hunck T, Gao Y, Lessard MD, Courchaine E, Barentine AES, Machyna M, Botti V, Qin A, Gbyli R, Patel A, Song Y, Kiefer L, Viero G, Neuenkirchen N, Lin H, Bewersdorf J, Simon MD, Neugebauer KM, Tebaldi T, Halene S. Precision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies. Molecular Cell 2022, 82: 1107-1122.e7. PMID: 35303483, PMCID: PMC8988922, DOI: 10.1016/j.molcel.2022.02.025.Peer-Reviewed Original ResearchCitationsAltmetric
2021
20 years of Developmental Cell: Looking back.
Chory J, Olson EN, Solnica-Krezel L, Munro S, Fuchs E, St Johnston D, Lefebvre V, Coupland G, Millar SE, Lin H. 20 years of Developmental Cell: Looking back. Developmental Cell 2021, 56: 3181-3184. PMID: 34875223, DOI: 10.1016/j.devcel.2021.11.014.Peer-Reviewed Original ResearchMaternal Piwi regulates primordial germ cell development to ensure the fertility of female progeny in Drosophila
Gonzalez LE, Tang X, Lin H. Maternal Piwi regulates primordial germ cell development to ensure the fertility of female progeny in Drosophila. Genetics 2021, 219: iyab091. PMID: 34142134, PMCID: PMC8757300, DOI: 10.1093/genetics/iyab091.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPIWI-interacting RNAsGermline developmentPiwi knockdownPIWI proteinsEarly embryosPiwi/piRNA complexesPIWI/piRNA pathwayFemale progenyPrimordial germ cell developmentGermline sex determinationLoss of PiwiGermline stem cellsDrosophila early embryosGerm cell developmentGerm cell proliferationGonad coalescencePiRNA complexesPiRNA pathwayPiRNA poolTransposon suppressionZygotic genesEmbryonic germlineEmbryonic functionEarly embryogenesisPiwiCPA-seq reveals small ncRNAs with methylated nucleosides and diverse termini
Wang H, Huang R, Li L, Zhu J, Li Z, Peng C, Zhuang X, Lin H, Shi S, Huang P. CPA-seq reveals small ncRNAs with methylated nucleosides and diverse termini. Cell Discovery 2021, 7: 25. PMID: 33867522, PMCID: PMC8053708, DOI: 10.1038/s41421-021-00265-2.Peer-Reviewed Original ResearchCitationsAltmetricConceptsSmall noncoding RNAsMethylated nucleosidesHepatic reprogrammingPolynucleotide kinaseHigh-throughput sequencingSRNA transcriptomeTissue-specific differencesSmall ncRNAsT4 polynucleotide kinaseNoncoding RNAsAdapter ligationMouse tissuesAcid pyrophosphataseReprogrammingComplex landscapeMethylationTerminusReverse transcriptionRNASequencingMentorship in Science: Response to AlShebli et al., Nature Communications 2020.
Mummery C, Little M, Lin H, Clark A, Zaret K, Srivastava D, Fuchs E, Watt F, Temple S. Mentorship in Science: Response to AlShebli et al., Nature Communications 2020. Stem Cell Reports 2021, 16: 1-2. PMID: 33440177, PMCID: PMC7815941, DOI: 10.1016/j.stemcr.2020.12.016.Peer-Reviewed Original ResearchRoles of piRNAs in transposon and pseudogene regulation of germline mRNAs and lncRNAs
Wang C, Lin H. Roles of piRNAs in transposon and pseudogene regulation of germline mRNAs and lncRNAs. Genome Biology 2021, 22: 27. PMID: 33419460, PMCID: PMC7792047, DOI: 10.1186/s13059-020-02221-x.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPIWI-interacting RNAsPIWI proteinsRole of piRNAsPIWI-piRNA pathwayRNA-binding proteinSmall noncoding RNAsGermline mRNAsGermline developmentNoncoding RNAsRegulatory relationshipsGerm cellsRNAProteinTransposonMajor classesRNA levelsRecent studiesExpressionGenomeSubfamiliesGermlineLncRNAsMajor constituentsMRNARegulation
Academic Achievements & Community Involvement
activity International Society for Stem Cell Research (ISSCR)
Public ServicePresidentDetails07/01/2022 - Presenthonor Member
National AwardNational Academy of MedicineDetails10/21/2024United Stateshonor Foreign Member
International AwardChinese Academy of SciencesDetails10/01/2021Chinahonor Member
National AwardUS National Academy of SciencesDetails05/01/2018United Stateshonor Member
National AwardAmerican Academy of Arts and SciencesDetails04/16/2018United States
News & Links
News
- November 01, 2024
Fikrig, Lin, Elected to National Academy of Medicine
- October 21, 2024
National Academy of Medicine Elects Two From Yale School of Medicine
- April 02, 2024Source: American Academy of Arts & Sciences
Amory Prize Is Presented to Haifan Lin
- February 01, 2024
Haifan Lin Earns the Francis Amory Prize
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