Timothy E O'sullivan

Title(s)Associate Professor, MIMG
SchoolMedicine
ORCID ORCID Icon0000-0003-1435-8188 Additional info
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    Collapse Biography 
    Collapse Education and Training
    Cornell University, Ithaca, NYBS12/2008Biomedical Engineering
    UCSD, San Diego, CAPhD9/2012Cancer Immunology
    Memorial Sloan Kettering Cancer Center, New York, NY6/2017Immunology
    Collapse Awards and Honors
    UCLA2022Regeneron New Investigator Award for Excellence in Cytokine and Interferon Research
    UCLA2021UCLA Life Sciences Excellence in Research Award
    UCLA2019UCSD-UCLA Diabetes Research Center Junior Faculty Award
    MSKCC2016AAI 2016 Thermo Fisher Trainee Achievement Award
    MSKCC2015  - 2017American Cancer Society Postdoctoral Fellowship

    Collapse Overview 
    Collapse Overview
    The O'Sullivan lab takes a collaborative interdisciplinary cyclical translation approach to discover new therapeutics that harness the power of the immune system. Starting with clinical datasets, we model cell-cell interactions and critical gene regulatory networks to understand the main mechanisms that drive disease during cancer, obesity, viral infection, and tissue injury. We then model these mechanisms using clinically relevant mouse models to discover conserved pathways that can be either drugged or engineered to enhance immune function. We focus on 3 fundamental research questions that have resulted in groundbreaking discoveries:

    1. What are the critical gene regulatory networks in human innate immunity?

    Although decades of research using mouse models have contributed to our understanding of the innate immune system, many findings in mice do not translate to humans. Furthermore, transcriptomics experiments in human innate immune cells suggest that the pathways induced in response to pro-inflammatory signals can be distinct from those in mice. These findings suggest that there is a pressing need to understand the molecular mechanisms that regulate human innate immunity. Our research program is designed to address this need through targeted CRISPR screens and bioinformatic analyses of patient samples.

    2. What are the mechanisms that regulate the lifespan of innate immune cells?

    Natural Killer (NK) cells are unique in that they share attributes of both the innate and adaptive immune system. NK cells can undergo clonal proliferation, contraction, and memory formation in response to viral infections such as cytomegalovirus (CMV). We are fascinated with understanding how a normally short-lived cell (~7 days) can dramatically enhance its lifespan to over a year following viral infection. Another arm of our research program is dedicated to understanding the molecular mechanisms that regulate NK cell persistence.

    3. How is inflammation initiated and maintained by the innate immune system?

    A complete immune response is enabled by the concerted activation of tissue-resident and circulating immune cells. However, we are only beginning to understand the role of tissue-resident immune cells in host physiology and disease. Our research interests have focused on the role of tissue-resident type 1 innate immune cells (cDC1, NK cells, ILC1) in host protection and pathology in response to pathogen-induced and sterile inflammation.
    Collapse Websites

    Collapse Research 
    Collapse Research Activities and Funding
    Predicting Primary Immune Deficiencies in Innate Immunity
    Hypothesis Fund Oct 1, 2023 - Mar 30, 2025
    Sex Differences in NK Cells Mediated by X-linked UTX
    NIH R01AI174519Jul 7, 2023 - Jun 30, 2028
    Role: Co-Investigator
    Understanding the transcriptional control of Natural Killer cell persistence in vivo
    Xyphos Biosciences Inc. Nov 1, 2022 - Oct 31, 2023
    Mechanisms of Tissue-Resident Immunity to Metastasis
    UC CRCC CRN-20-637105Jan 1, 2020 - Dec 30, 2020
    Transcriptional mechanisms of natural killer cell responses during mouse cytomegalovirus infection
    NIH R01AI145997May 6, 2019 - Apr 30, 2024
    Role: Principal Investigator
    Determining the contribution of adipose-resident dendritic cells to obesity-associated inflammation and insulin resistance
    NIDDK P30 DK063491Jul 1, 2018 - Jun 30, 2020

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. No time to die: Epigenetic regulation of natural killer cell survival. Immunol Rev. 2024 Mar 01. Hermans L, O'Sullivan TE. PMID: 38426615.
      View in: PubMed   Mentions:    Fields:    
    2. Suppression of adaptive NK cell expansion by macrophage-mediated phagocytosis inhibited by 2B4-CD48. Cell Rep. 2024 Feb 21; 43(3):113800. Li R, Galindo CC, Davidson D, Guo H, Zhong MC, Qian J, Li B, Ruzsics Z, Lau CM, O'Sullivan TE, Vidal SM, Sun JC, Veillette A. PMID: 38386559.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    3. Adipose cDC1s contribute to obesity-associated inflammation through STING-dependent IL-12 production. Nat Metab. 2023 Dec; 5(12):2237-2252. Hildreth AD, Padilla ET, Gupta M, Wong YY, Sun R, Legala AR, O'Sullivan TE. PMID: 37996702.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimals
    4. Regulation of systemic metabolism by tissue-resident immune cell circuits. Immunity. 2023 06 13; 56(6):1168-1186. Li JH, Hepworth MR, O'Sullivan TE. PMID: 37315533; PMCID: PMC10321269.
      View in: PubMed   Mentions: 2     Fields:    Translation:Humans
    5. The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences. Nat Immunol. 2023 05; 24(5):780-791. Cheng MI, Li JH, Riggan L, Chen B, Tafti RY, Chin S, Ma F, Pellegrini M, Hrncir H, Arnold AP, O'Sullivan TE, Su MA. PMID: 36928413.
      View in: PubMed   Mentions: 14     Fields:    Translation:HumansAnimalsCells
    6. Sterile liver injury induces a protective tissue-resident cDC1-ILC1 circuit through cDC1-intrinsic cGAS-STING-dependent IL-12 production. Cell Rep. 2023 02 28; 42(2):112141. Hildreth AD, Padilla ET, Tafti RY, Legala AR, O'Sullivan TE. PMID: 36807146; PMCID: PMC10435668.
      View in: PubMed   Mentions: 2     Fields:    Translation:HumansCells
    7. Infection induces tissue-resident memory NK cells that safeguard tissue health. Immunity. 2023 03 14; 56(3):531-546.e6. Schuster IS, Sng XYX, Lau CM, Powell DR, Weizman OE, Fleming P, Neate GEG, Voigt V, Sheppard S, Maraskovsky AI, Daly S, Koyama M, Hill GR, Turner SJ, O'Sullivan TE, Sun JC, Andoniou CE, Degli-Esposti MA. PMID: 36773607; PMCID: PMC10360410.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansAnimalsCells
    8. Single-cell RNA sequencing identifies a population of human liver-type ILC1s. Cell Rep. 2023 01 31; 42(1):111937. Krämer B, Nalin AP, Ma F, Eickhoff S, Lutz P, Leonardelli S, Goeser F, Finnemann C, Hack G, Raabe J, ToVinh M, Ahmad S, Hoffmeister C, Kaiser KM, Manekeller S, Branchi V, Bald T, Hölzel M, Hüneburg R, Nischalke HD, Semaan A, Langhans B, Kaczmarek DJ, Benner B, Lordo MR, Kowalski J, Gerhardt A, Timm J, Toma M, Mohr R, Türler A, Charpentier A, van Bremen T, Feldmann G, Sattler A, Kotsch K, Abdallah AT, Strassburg CP, Spengler U, Carson WE, Mundy-Bosse BL, Pellegrini M, O'Sullivan TE, Freud AG, Nattermann J. PMID: 36640314; PMCID: PMC9950534.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansCells
    9. Leukemia inhibitory factor protects against graft-versus-host disease while preserving graft-versus-leukemia activity. Blood. 2022 11 10; 140(19):2076-2090. Wang J, Chang CY, Yang X, Zhou F, Liu J, Zhu S, Yu XZ, Liu C, O'Sullivan TE, Xie P, Feng Z, Hu W. PMID: 35981499; PMCID: PMC9837439.
      View in: PubMed   Mentions: 5     Fields:    Translation:Animals
    10. The transcription factor Fli1 restricts the formation of memory precursor NK cells during viral infection. Nat Immunol. 2022 04; 23(4):556-567. Riggan L, Ma F, Li JH, Fernandez E, Nathanson DA, Pellegrini M, O'Sullivan TE. PMID: 35288713; PMCID: PMC8989647.
      View in: PubMed   Mentions: 5     Fields:    Translation:AnimalsCells
    11. Back to the Future: Spatiotemporal Determinants of NK Cell Antitumor Function. Front Immunol. 2021; 12:816658. Li JH, O'Sullivan TE. PMID: 35082797; PMCID: PMC8785903.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansAnimalsCells
    12. Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity. Nat Immunol. 2021 05; 22(5):639-653. Hildreth AD, Ma F, Wong YY, Sun R, Pellegrini M, O'Sullivan TE. PMID: 33907320; PMCID: PMC8102391.
      View in: PubMed   Mentions: 96     Fields:    Translation:HumansCells
    13. Arrested development: suppression of NK cell function in the tumor microenvironment. Clin Transl Immunology. 2021; 10(1):e1238. Riggan L, Shah S, O'Sullivan TE. PMID: 33456775; PMCID: PMC7797224.
      View in: PubMed   Mentions: 25  
    14. CRISPR-Cas9 Ribonucleoprotein-Mediated Genomic Editing in Primary Innate Immune Cells. STAR Protoc. 2020 12 18; 1(3):100113. Hildreth AD, Riggan L, O'Sullivan TE. PMID: 33377009; PMCID: PMC7756923.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansAnimalsCells
    15. CRISPR-Cas9 Ribonucleoprotein-Mediated Genomic Editing in Mature Primary Innate Immune Cells. Cell Rep. 2020 05 19; 31(7):107651. Riggan L, Hildreth AD, Rolot M, Wong YY, Satyadi W, Sun R, Huerta C, O'Sullivan TE. PMID: 32433960; PMCID: PMC7294876.
      View in: PubMed   Mentions: 17     Fields:    Translation:Animals
    16. Type 1 Innate Lymphoid Cells Protect Mice from Acute Liver Injury via Interferon-γ Secretion for Upregulating Bcl-xL Expression in Hepatocytes. Immunity. 2020 01 14; 52(1):96-108.e9. Nabekura T, Riggan L, Hildreth AD, O'Sullivan TE, Shibuya A. PMID: 31810881; PMCID: PMC8108607.
      View in: PubMed   Mentions: 34     Fields:    Translation:AnimalsCells
    17. Dazed and Confused: NK Cells. Front Immunol. 2019; 10:2235. O'Sullivan TE. PMID: 31616419; PMCID: PMC6763593.
      View in: PubMed   Mentions: 16     Fields:    Translation:HumansCells
    18. True Detective: Unraveling Group 1 Innate Lymphocyte Heterogeneity. Trends Immunol. 2019 10; 40(10):909-921. Riggan L, Freud AG, O'Sullivan TE. PMID: 31500958; PMCID: PMC6823149.
      View in: PubMed   Mentions: 30     Fields:    Translation:HumansAnimalsCells
    19. Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12. Nat Immunol. 2019 08; 20(8):1004-1011. Weizman OE, Song E, Adams NM, Hildreth AD, Riggan L, Krishna C, Aguilar OA, Leslie CS, Carlyle JR, Sun JC, O'Sullivan TE. PMID: 31263280; PMCID: PMC6697419.
      View in: PubMed   Mentions: 42     Fields:    Translation:AnimalsCells
    20. Tissue-Resident Innate and Innate-Like Lymphocyte Responses to Viral Infection. Viruses. 2019 03 19; 11(3). Hildreth AD, O'Sullivan TE. PMID: 30893756; PMCID: PMC6466361.
      View in: PubMed   Mentions: 8     Fields:    Translation:HumansAnimalsCells
    21. Determination of the Fate and Function of Innate Lymphoid Cells Following Adoptive Transfer of Innate Lymphoid Cell Precursors. Methods Mol Biol. 2018; 1799:109-119. O'Sullivan TE, Sun JC. PMID: 29956148.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    22. Core-binding factor β and Runx transcription factors promote adaptive natural killer cell responses. Sci Immunol. 2017 12 08; 2(18). Rapp M, Lau CM, Adams NM, Weizman OE, O'Sullivan TE, Geary CD, Sun JC. PMID: 29222089; PMCID: PMC6265048.
      View in: PubMed   Mentions: 43     Fields:    Translation:AnimalsCells
    23. ILC1 Confer Early Host Protection at Initial Sites of Viral Infection. Cell. 2017 Nov 02; 171(4):795-808.e12. Weizman OE, Adams NM, Schuster IS, Krishna C, Pritykin Y, Lau C, Degli-Esposti MA, Leslie CS, Sun JC, O'Sullivan TE. PMID: 29056343; PMCID: PMC5687850.
      View in: PubMed   Mentions: 219     Fields:    Translation:AnimalsCells
    24. Innate Lymphoid Cell Immunometabolism. J Mol Biol. 2017 11 24; 429(23):3577-3586. O'Sullivan TE, Sun JC. PMID: 28867535; PMCID: PMC5719889.
      View in: PubMed   Mentions: 11     Fields:    Translation:HumansAnimalsCells
    25. NK Cell Responses Redefine Immunological Memory. J Immunol. 2016 10 15; 197(8):2963-2970. Adams NM, O'Sullivan TE, Geary CD, Karo JM, Amezquita RA, Joshi NS, Kaech SM, Sun JC. PMID: 27824591; PMCID: PMC5108457.
      View in: PubMed   Mentions: 15     Fields:    Translation:HumansAnimalsCells
    26. Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance. Cell Rep. 2016 08 30; 16(9):2348-58. Saddawi-Konefka R, Seelige R, Gross ET, Levy E, Searles SC, Washington A, Santosa EK, Liu B, O'Sullivan TE, Harismendy O, Bui JD. PMID: 27545889; PMCID: PMC5007173.
      View in: PubMed   Mentions: 60     Fields:    Translation:HumansAnimalsCells
    27. Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance. Immunity. 2016 08 16; 45(2):428-41. O'Sullivan TE, Rapp M, Fan X, Weizman OE, Bhardwaj P, Adams NM, Walzer T, Dannenberg AJ, Sun JC. PMID: 27496734; PMCID: PMC5004886.
      View in: PubMed   Mentions: 149     Fields:    Translation:HumansAnimalsCells
    28. Atg5 Is Essential for the Development and Survival of Innate Lymphocytes. Cell Rep. 2016 05 31; 15(9):1910-9. O'Sullivan TE, Geary CD, Weizman OE, Geiger TL, Rapp M, Dorn GW, Overholtzer M, Sun JC. PMID: 27210760; PMCID: PMC4889506.
      View in: PubMed   Mentions: 43     Fields:    Translation:AnimalsCells
    29. Natural Killer Cell Memory. Immunity. 2015 Oct 20; 43(4):634-45. O'Sullivan TE, Sun JC, Lanier LL. PMID: 26488815; PMCID: PMC4621966.
      View in: PubMed   Mentions: 168     Fields:    Translation:HumansAnimalsCells
    30. BNIP3- and BNIP3L-Mediated Mitophagy Promotes the Generation of Natural Killer Cell Memory. Immunity. 2015 Aug 18; 43(2):331-42. O'Sullivan TE, Johnson LR, Kang HH, Sun JC. PMID: 26253785; PMCID: PMC5737626.
      View in: PubMed   Mentions: 154     Fields:    Translation:AnimalsCells
    31. Generation of Natural Killer Cell Memory during Viral Infection. J Innate Immun. 2015; 7(6):557-62. O'Sullivan TE, Sun JC. PMID: 25823611; PMCID: PMC4581887.
      View in: PubMed   Mentions: 11     Fields:    Translation:HumansAnimalsCells
    32. Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens. J Exp Med. 2014 Aug 25; 211(9):1723-31. Geiger TL, Abt MC, Gasteiger G, Firth MA, O'Connor MH, Geary CD, O'Sullivan TE, van den Brink MR, Pamer EG, Hanash AM, Sun JC. PMID: 25113970; PMCID: PMC4144732.
      View in: PubMed   Mentions: 137     Fields:    Translation:AnimalsCells
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